|
1
|
Ghanbari A. Beneficial Effects of Exercise in Neuropathic Pain: An Overview of the Mechanisms Involved. Pain Res Manag 2025; 2025:3432659. [PMID: 40040749 PMCID: PMC11879594 DOI: 10.1155/prm/3432659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Accepted: 02/08/2025] [Indexed: 03/06/2025]
Abstract
Neuropathic pain is a prevalent issue that often arises following injuries to the peripheral or central nervous system. Unfortunately, there is currently no definitive and flawless treatment available to alleviate this type of pain. However, exercise has emerged as a promising nonpharmacological and adjunctive approach, demonstrating a significant impact in reducing pain intensity. This is why physical therapy is considered a beneficial approach for diminishing pain and promoting functional recovery following nerve injuries. Regular physical activity exerts its hypoalgesic effects through a diverse array of mechanisms. These include inhibiting oxidative stress, suppressing inflammation, and modulating neurotransmitter levels, among others. It is possible that multiple activated mechanisms may coexist within an individual. However, the priming mechanism does not need to be the same across all subjects. Each person's response to physical activity and pain modulation may vary depending on their unique physiological and genetic factors. In this review, we aimed to provide a concise overview of the mechanisms underlying the beneficial effects of regular exercise on neuropathic pain. We have discussed several key mechanisms that contribute to the improvement of neuropathic pain through exercise. However, it is important to note that this is not an exhaustive analysis, and there may be other mechanisms at play. Our goal was to provide a brief yet informative exploration of the topic.
Collapse
Affiliation(s)
- Ali Ghanbari
- Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran
- Department of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| |
Collapse
|
|
2
|
Ma L, Fan YY, Li BL, Xu F, Zhao X. Antiallodynic and antihyperalgesic effects of decursin associated with correcting mitochondrial dysfunction and oxidative stress in type 1 diabetic mice. Chem Biol Interact 2024; 403:111249. [PMID: 39299373 DOI: 10.1016/j.cbi.2024.111249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 09/16/2024] [Accepted: 09/17/2024] [Indexed: 09/22/2024]
Abstract
A substantial proportion of diabetic patients suffer a debilitating and persistent pain state, known as peripheral painful neuropathy that necessitates improved therapy or antidote. Decursin, a major active ingredient from Angelica gigas Nakai, has been reported to possess antidepressant activity in preclinical studies. As antidepressants have been typically used as standard agents against persistent neuropathic pain, this study aimed to probe the effect of decursin on neuropathic pain associated with streptozotocin-induced type 1 diabetes in male C57BL6J mice. The Hargreaves test and the von Frey test were used to assess pain-like behaviors, shown as heat hyperalgesia and mechanical allodynia respectively. Chronic treatment of diabetic mice with decursin not only ameliorated the established symptoms of heat hyperalgesia and mechanical allodynia, but also arrested the development of these pain states given preemptively at low doses. Although decursin treatment hardly impacted on metabolic disturbance in diabetic mice, it ameliorated exacerbated oxidative stress in pain-associated tissues, improved mitochondrial bioenergetics in dorsal root ganglion neurons, and restored nerve conduction velocity and blood flow in sciatic nerves. Notably, the analgesic actions of decursin were modified by pharmacologically manipulating redox status and mitochondrial bioenergetics. These findings unveil the analgesic activity of decursin, an effect that is causally associated with its bioenergetics-enhancing and antioxidant effects, in mice with type 1 diabetes.
Collapse
Affiliation(s)
- Li Ma
- Department of Neurology, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei Province, China
| | - You-Ya Fan
- Department of Pharmacology and Zhejiang Key Lab of Pathophysiology, Ningbo University, Health Science Center, Ningbo, Zhejiang Province, China
| | - Ben-Ling Li
- School of Mathematics and Statistics, Ningbo University, Ningbo, Zhejiang province, China
| | - Feng Xu
- Central Laboratory, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China
| | - Xin Zhao
- Department of Pharmacology and Zhejiang Key Lab of Pathophysiology, Ningbo University, Health Science Center, Ningbo, Zhejiang Province, China.
| |
Collapse
|
|
3
|
Palazzo E, Marabese I, Ricciardi F, Guida F, Luongo L, Maione S. The influence of glutamate receptors on insulin release and diabetic neuropathy. Pharmacol Ther 2024; 263:108724. [PMID: 39299577 DOI: 10.1016/j.pharmthera.2024.108724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 09/09/2024] [Accepted: 09/16/2024] [Indexed: 09/22/2024]
Abstract
Diabetes causes macrovascular and microvascular complications such as peripheral neuropathy. Glutamate regulates insulin secretion in pancreatic β-cells, and its increased activity in the central nervous system is associated with peripheral neuropathy in animal models of diabetes. One strategy to modulate glutamatergic activity consists in the pharmacological manipulation of metabotropic glutamate receptors (mGluRs), which, compared to the ionotropic receptors, allow for a fine-tuning of neurotransmission that is compatible with therapeutic interventions. mGluRs are a family of eight G-protein coupled receptors classified into three groups (I-III) based on sequence homology, transduction mechanisms, and pharmacology. Activation of group II and III or inhibition of group I represents a strategy to counteract the glutamatergic hyperactivity associated with diabetic neuropathy. In this review article, we will discuss the role of glutamate receptors in the release of insulin and the development/treatment of diabetic neuropathy, with particular emphasis on their manipulation to prevent the glutamatergic hyperactivity associated with diabetic neuropathy.
Collapse
Affiliation(s)
- Enza Palazzo
- Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli", via Costantinopoli 16, 80138 Naples, Italy.
| | - Ida Marabese
- Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli", via Costantinopoli 16, 80138 Naples, Italy
| | - Federica Ricciardi
- Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli", via Costantinopoli 16, 80138 Naples, Italy
| | - Francesca Guida
- Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli", via Costantinopoli 16, 80138 Naples, Italy
| | - Livio Luongo
- Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli", via Costantinopoli 16, 80138 Naples, Italy
| | - Sabatino Maione
- Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli", via Costantinopoli 16, 80138 Naples, Italy
| |
Collapse
|
|
4
|
Chen W, Wu JY, Fan YY, Li BL, Yuan HB, Zhao X. Purpurin ameliorated neuropathic allodynia and hyperalgesia by modulating neuronal mitochondrial bioenergetics and redox status in type 1 diabetic mice. Eur J Pharmacol 2024; 978:176749. [PMID: 38897444 DOI: 10.1016/j.ejphar.2024.176749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 05/29/2024] [Accepted: 06/16/2024] [Indexed: 06/21/2024]
Abstract
A substantial proportion of diabetic patients suffer a debilitating and persistent pain state, known as peripheral painful neuropathy that necessitates improved therapy or antidote. Purpurin, a natural anthraquinone compound from Rubia tinctorum L., has been reported to possess antidepressant activity in preclinical studies. As antidepressants have been typically used as standard agents against persistent neuropathic pain, this study aimed to probe the effect of purpurin on neuropathic pain associated with streptozotocin-induced type 1 diabetes in male C57BL6J mice. The Hargreaves test and the von Frey test were used to assess the pain-like behaviors, shown as heat hyperalgesia and mechanical allodynia respectively. Chronic treatment of diabetic mice with purpurin not only ameliorated the established symptoms of heat hyperalgesia and mechanical allodynia, but also arrested the development of these pain states given preemptively at low doses. Although purpurin treatment hardly impacted on metabolic disturbance in diabetic mice, it ameliorated exacerbated oxidative stress in pain-associated tissues, improved mitochondrial bioenergetics in dorsal root ganglion neurons and restored nerve conduction velocity in sciatic nerves. Notably, the analgesic actions of purpurin were modified by pharmacologically manipulating redox status and mitochondrial bioenergetics. These findings unveil the analgesic activity of purpurin, an effect that is causally associated with its bioenergetics-enhancing and antioxidant effects, in mice with type 1 diabetes.
Collapse
Affiliation(s)
- Wei Chen
- Department of Anesthesiology, The Changzheng Hospital, The Second Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Jia-Yi Wu
- Department of Pharmacology and Zhejiang Key Lab of Pathophysiology, Ningbo University, Health Science Center, Ningbo, Zhejiang province, China
| | - You-Ya Fan
- Department of Pharmacology and Zhejiang Key Lab of Pathophysiology, Ningbo University, Health Science Center, Ningbo, Zhejiang province, China
| | - Ben-Ling Li
- School of Mathematics and Statistics, Ningbo University, Ningbo, Zhejiang province, China
| | - Hong-Bin Yuan
- Department of Anesthesiology, The Changzheng Hospital, The Second Affiliated Hospital of Naval Medical University, Shanghai, China.
| | - Xin Zhao
- Department of Pharmacology and Zhejiang Key Lab of Pathophysiology, Ningbo University, Health Science Center, Ningbo, Zhejiang province, China.
| |
Collapse
|
|
5
|
Vachirarojpisan T, Srivichit B, Vaseenon S, Powcharoen W, Imerb N. Therapeutic roles of coenzyme Q10 in peripheral nerve injury-induced neurosensory disturbances: Mechanistic insights from injury to recovery. Nutr Res 2024; 129:55-67. [PMID: 39217889 DOI: 10.1016/j.nutres.2024.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 07/31/2024] [Accepted: 07/31/2024] [Indexed: 09/04/2024]
Abstract
Peripheral nerve injuries (PNIs) are prevalent conditions mainly resulting from systemic causes, including autoimmune diseases and diabetes mellitus, or local causes, for example, chemical injury and perioperative nerve injury, which can cause a varying level of neurosensory disturbances (NSDs). Coenzyme Q10 (CoQ10) is an essential regulator of mitochondrial respiration and oxidative metabolism. Here, we review the pathophysiology of NSDs caused by PNIs, the current understanding of CoQ10's bioactivities, and its potential therapeutic roles in nerve regeneration, based on evidence from experimental and clinical studies involving CoQ10 supplementation. In summary, CoQ10 supplementation shows promise as a neuroprotective agent, potentially enhancing treatment efficacy for NSDs by reducing oxidative stress and inflammation. Future studies should focus on well-designed clinical trials with large sample sizes, using CoQ10 formulations with proven bioavailability and varying treatment duration, to further elucidate its neuroprotective effects and to optimize nerve regeneration in PNIs-induced NSDs.
Collapse
Affiliation(s)
- Thanyaphorn Vachirarojpisan
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
| | - Bhumrapee Srivichit
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
| | - Savitri Vaseenon
- Department of Restorative Dentistry and Periodontology, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
| | - Warit Powcharoen
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
| | - Napatsorn Imerb
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
| |
Collapse
|
|
6
|
Yan S, Lu J, Chen B, Yuan L, Chen L, Ju L, Cai W, Wu J. The Multifaceted Role of Alpha-Lipoic Acid in Cancer Prevention, Occurrence, and Treatment. Antioxidants (Basel) 2024; 13:897. [PMID: 39199143 PMCID: PMC11351715 DOI: 10.3390/antiox13080897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 07/19/2024] [Accepted: 07/23/2024] [Indexed: 09/01/2024] Open
Abstract
Alpha-lipoic acid (ALA) is a naturally occurring compound synthesized by mitochondria and widely distributed in both animal and plant tissues. It primarily influences cellular metabolism and oxidative stress networks through its antioxidant properties and is an important drug for treating metabolic diseases associated with oxidative damage. Nevertheless, research indicates that the mechanism by which ALA affects cancer cells is distinct from that observed in normal cells, exhibiting pro-oxidative properties. Therefore, this review aims to describe the main chemical and biological functions of ALA in the cancer environment, including its mechanisms and effects in tumor prevention and anticancer activity, as well as its role as an adjunctive drug in cancer therapy. We specifically focus on the interactions between ALA and various carcinogenic and anti-carcinogenic pathways and discuss ALA's pro-oxidative capabilities in the unique redox environment of cancer cells. Additionally, we elaborate on ALA's roles in nanomedicine, hypoxia-inducible factors, and cancer stem cell research, proposing hypotheses and potential explanations for currently unresolved issues.
Collapse
Affiliation(s)
- Shuai Yan
- Medical School, Nantong University, Nantong 226300, China; (S.Y.); (J.L.); (B.C.)
| | - Jiajie Lu
- Medical School, Nantong University, Nantong 226300, China; (S.Y.); (J.L.); (B.C.)
| | - Bingqing Chen
- Medical School, Nantong University, Nantong 226300, China; (S.Y.); (J.L.); (B.C.)
| | - Liuxia Yuan
- Institute of Liver Diseases, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226300, China; (L.Y.); (L.C.); (L.J.)
| | - Lin Chen
- Institute of Liver Diseases, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226300, China; (L.Y.); (L.C.); (L.J.)
| | - Linglin Ju
- Institute of Liver Diseases, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226300, China; (L.Y.); (L.C.); (L.J.)
| | - Weihua Cai
- Department of Hepatobiliary Surgery, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226300, China;
| | - Jinzhu Wu
- Medical School, Nantong University, Nantong 226300, China; (S.Y.); (J.L.); (B.C.)
- Department of Hepatobiliary Surgery, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226300, China;
| |
Collapse
|
|
7
|
Uppaluri S, Jain MA, Ali H, Shingala J, Amin D, Ajwani T, Fatima I, Patel N, Kaka N, Sethi Y, Kapoor N. Pathogenesis and management of diabetic gastroparesis: An updated clinically oriented review. Diabetes Metab Syndr 2024; 18:102994. [PMID: 38579489 DOI: 10.1016/j.dsx.2024.102994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 02/25/2024] [Accepted: 03/20/2024] [Indexed: 04/07/2024]
Abstract
BACKGROUND AND AIMS Diabetic gastroparesis (DGp) is a common and preventable complication of uncontrolled diabetes mellitus (D.M.) and significantly affects the Quality of Life of patients. Diagnosis and management present as a clinical challenge due to the disease's complexity and limited effective therapeutic options. This review aims to comprehensively outline the pathogenesis, diagnosis, and management of diabetic gastroparesis, evaluating evolving approaches to guide clinicians and provide future recommendations. METHODS A literature review was conducted on scholarly databases of PubMed, Google Scholar, Scopus and Web of Science encompassing published articles, gray literature and relevant clinical guidelines. Data were synthesized and analyzed to provide a comprehensive overview of diabetic gastroparesis, focusing on pathogenesis, diagnosis, and management. RESULTS The review intricately explores the pathogenesis contributing to diabetic gastroparesis, emphasizing autonomic neuropathy, oxidative stress, inflammation, hormonal dysregulation, microbiota alterations, and gastrointestinal neuropathy. Primary management strategies are underscored, including lifestyle modifications, symptom relief, and glycemic control. The discussion encompasses pharmacological and surgical options, highlighting the importance of a multidisciplinary approach involving various healthcare professionals for comprehensive patient care. CONCLUSION This review offers a thorough understanding of pathogenesis, diagnosis, and management of diabetic gastroparesis, underlining evolving approaches for clinicians. A multidisciplinary approach is crucial to address both the physical and mental health aspects of diabetes and its complications.
Collapse
Affiliation(s)
- Srikar Uppaluri
- Kamineni Academy of Medical Sciences and Research Center, Hyderabad, India; PearResearch, Dehradun, India.
| | - Manisha Ashok Jain
- PearResearch, Dehradun, India; Shri Bhausaheb Hire Govt. Medical College, Dhule, Maharashtra, India.
| | - Hira Ali
- PearResearch, Dehradun, India; Chifeng University Medical College, China.
| | - Jay Shingala
- PearResearch, Dehradun, India; B.J. Medical College, Ahmedabad, India.
| | - Dhruti Amin
- PearResearch, Dehradun, India; GMERS Medical College and Hospital, Gotri, Vadodara, India.
| | - Trisha Ajwani
- PearResearch, Dehradun, India; Baroda Medical College, Gujarat, India.
| | - Irum Fatima
- PearResearch, Dehradun, India; Osmania Medical College, Hyderabad, India.
| | - Neil Patel
- PearResearch, Dehradun, India; GMERS Medical College, Himmatnagar, Gujarat, India.
| | - Nirja Kaka
- PearResearch, Dehradun, India; GMERS Medical College, Himmatnagar, Gujarat, India.
| | - Yashendra Sethi
- PearResearch, Dehradun, India; Government Doon Medical College, Dehradun, India.
| | - Nitin Kapoor
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India.
| |
Collapse
|
|
8
|
Baicus C, Purcarea A, von Elm E, Delcea C, Furtunescu FL. Alpha-lipoic acid for diabetic peripheral neuropathy. Cochrane Database Syst Rev 2024; 1:CD012967. [PMID: 38205823 PMCID: PMC10782777 DOI: 10.1002/14651858.cd012967.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2024]
Abstract
BACKGROUND Diabetic peripheral neuropathy (DPN) is a frequent complication in people living with type 1 or type 2 diabetes. There is currently no effective treatment for DPN. Although alpha-lipoic acid (ALA, also known as thioctic acid) is widely used, there is no consensus about its benefits and harms. OBJECTIVES To assess the effects of alpha-lipoic acid as a disease-modifying agent in people with diabetic peripheral neuropathy. SEARCH METHODS On 11 September 2022, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and two clinical trials registers. We also searched the reference lists of the included studies and relevant review articles for additional references not identified by the electronic searches. SELECTION CRITERIA We included randomised clinical trials (RCTs) that compared ALA with placebo in adults (aged 18 years or older) and that applied the study interventions for at least six months. There were no language restrictions. DATA COLLECTION AND ANALYSIS We used standard methods expected by Cochrane. The primary outcome was change in neuropathy symptoms expressed as changes in the Total Symptom Score (TSS) at six months after randomisation. Secondary outcomes were change in neuropathy symptoms at six to 12 months and at 12 to 24 months, change in impairment, change in any validated quality of life total score, complications of DPN, and adverse events. We assessed the certainty of the evidence using GRADE. MAIN RESULTS Our analysis incorporated three trials involving 816 participants. Two studies included people with type 1 or type 2 diabetes, while one study included only people with type 2 diabetes. The duration of treatment was between six months and 48 months. We judged all studies at high risk of overall bias due to attrition. ALA compared with placebo probably has little or no effect on neuropathy symptoms measured by TSS (lower score is better) after six months (mean difference (MD) -0.16 points, 95% confidence interval (CI) -0.83 to 0.51; 1 study, 330 participants; moderate-certainty evidence). The CI of this effect estimate did not contain the minimal clinically important difference (MCID) of 0.97 points. ALA compared with placebo may have little or no effect on impairment measured by the Neuropathy Impairment Score-Lower Limbs (NIS-LL; lower score is better) after six months (MD -1.02 points, 95% CI -2.93 to 0.89; 1 study, 245 participants; low-certainty evidence). However, we cannot rule out a significant benefit, because the lower limit of the CI surpassed the MCID of 2 points. There is probably little or no difference between ALA and placebo in terms of adverse events leading to cessation of treatment within six months (risk ratio (RR) 1.48, 95% CI 0.50 to 4.35; 3 studies, 1090 participants; moderate-certainty evidence). No studies reported quality of life or complications associated with DPN. AUTHORS' CONCLUSIONS Our analysis suggests that ALA probably has little or no effect on neuropathy symptoms or adverse events at six months, and may have little or no effect on impairment at six months. All the studies were at high risk of attrition bias. Therefore, future RCTs should ensure complete follow-up and transparent reporting of any participants missing from the analyses.
Collapse
Affiliation(s)
- Cristian Baicus
- Internal Medicine, Colentina University Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Adrian Purcarea
- Department of Fundamental, Prophylactic and Clinical Sciences, Faculty of Medicine, Transilvania University, Brasov, Romania
- Internist.ro Clinic, Brasov, Romania
| | - Erik von Elm
- Cochrane Switzerland, Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland
| | - Caterina Delcea
- Internal Medicine, Colentina University Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Florentina L Furtunescu
- Public Health and Management, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| |
Collapse
|
|
9
|
Schicht M, Farger J, Wedel S, Sisignano M, Scholich K, Geisslinger G, Perumal N, Grus FH, Singh S, Sahin A, Paulsen F, Lütjen-Drecoll E. Ocular surface changes in mice with streptozotocin-induced diabetes and diabetic polyneuropathy. Ocul Surf 2024; 31:43-55. [PMID: 38141818 DOI: 10.1016/j.jtos.2023.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Revised: 12/13/2023] [Accepted: 12/20/2023] [Indexed: 12/25/2023]
Abstract
PURPOSE Diabetes mellitus (DM) is a leading risk factor for corneal neuropathy and dry eye disease (DED). Another common consequence of DM is diabetic peripheral polyneuropathy (DPN). Both complications affect around 50 % of the DM patients but the relationship between DM, DED and DPN remains unclear. METHODS In this study, we examined mice with early onset of DM and PN after streptozotocin (STZ)-induced diabetes (DPN). We compared the early morphological changes of the sciatic nerve, dorsal root and trigeminal ganglia with the changes in the ocular surface, including tear proteomic and we also investigated respective changes in the gene expressions and morphological alterations in the eye tissues involved in tear production. RESULTS The lacrimal gland, conjunctival goblet cells and cornea showed morphological changes along with alterations in tear proteins without any obvious signs of ocular surface inflammation. The gene expression for respectively altered tear proteins i.e., of Clusterin in cornea, Car6, Adh3a1, and Eef1a1 in eyelids, and Pigr in the lacrimal gland also showed significant changes compared to control mice. In the trigeminal ganglia like in the dorsal root ganglia neuronal cells showed swollen mitochondria and, in the latter, there was a significant increase of NADPH oxidases and MMP9 suggestive of oxidative and neuronal stress. In the dorsal root ganglia and the sciatic nerve, there was an upregulation of a number of pro-inflammatory cytokines and pain-mediating chemokines. CONCLUSION The early ocular changes in DM Mice only affect the lacrimal gland. Which, is reflected in the tear film composition of DPN mice. Due to the high protein concentration in tear fluid in humans, proteomic analysis in addition to noninvasive investigation of goblet cells and cornea can serve as a tools for the early diagnosis of DPN, DED in clinical practice. Early treatment could delay or even prevent the ocular complications of DM such as DED and PN.
Collapse
Affiliation(s)
- Martin Schicht
- Institute of Functional and Clinical Anatomy, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
| | - Jessica Farger
- Institute of Functional and Clinical Anatomy, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Saskia Wedel
- Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany
| | - Marco Sisignano
- Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Frankfurt am Main, Department of Experimental and Translational Ophthalmology, Germany
| | - Klaus Scholich
- Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Frankfurt am Main, Department of Experimental and Translational Ophthalmology, Germany
| | - Gerd Geisslinger
- Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Frankfurt am Main, Department of Experimental and Translational Ophthalmology, Germany
| | - Natarajan Perumal
- Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Franz H Grus
- Experimental and Translational Ophthalmology, Department of Ophthalmology, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Swati Singh
- Institute of Functional and Clinical Anatomy, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Afsun Sahin
- Department of Ophthalmology, Koc University Medical School, Istanbul, Turkey
| | - Friedrich Paulsen
- Institute of Functional and Clinical Anatomy, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Elke Lütjen-Drecoll
- Institute of Functional and Clinical Anatomy, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| |
Collapse
|
|
10
|
Jang HN, Oh TJ. Pharmacological and Nonpharmacological Treatments for Painful Diabetic Peripheral Neuropathy. Diabetes Metab J 2023; 47:743-756. [PMID: 37670573 PMCID: PMC10695723 DOI: 10.4093/dmj.2023.0018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 06/28/2023] [Indexed: 09/07/2023] Open
Abstract
Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%-25% of patients with diabetes experience neuropathic pain, referred to as "painful DPN." Appropriate treatment of painful DPN is important because this pain contributes to a poor quality of life by causing sleep disturbance, anxiety, and depression. The basic principle for the management of painful DPN is to control hyperglycemia and other modifiable risk factors, but these may be insufficient for preventing or improving DPN. Because there is no promising diseasemodifying medication for DPN, the pain itself needs to be managed when treating painful DPN. Drugs for neuropathic pain, such as gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, alpha-lipoic acid, sodium channel blockers, and topical capsaicin, are used for the management of painful DPN. The U.S. Food and Drug Administration (FDA) has approved pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch as drugs for the treatment of painful DPN. Recently, spinal cord stimulation using electrical stimulation is approved by the FDA for the treatment for painful DPN. This review describes the currently available pharmacological and nonpharmacological treatments for painful DPN.
Collapse
Affiliation(s)
- Han Na Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Tae Jung Oh
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
|
11
|
Borgonetti V, Galeotti N. Honokiol-Rich Magnolia officinalis Bark Extract Attenuates Trauma-Induced Neuropathic Pain. Antioxidants (Basel) 2023; 12:1518. [PMID: 37627513 PMCID: PMC10451803 DOI: 10.3390/antiox12081518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 07/23/2023] [Accepted: 07/25/2023] [Indexed: 08/27/2023] Open
Abstract
Neuropathic pain (NP) affects about 8% of the general population. Current analgesic therapies have limited efficacy, making NP one of the most difficult to treat pain conditions. Evidence indicates that excessive oxidative stress can contribute to the onset of chronic NP and several natural antioxidant compounds have shown promising efficacy in NP models. Thus, this study aimed to investigate the pain-relieving activity of honokiol (HNK)-rich standardized extract of Magnolia officinalis Rehder & E. Wilson bark (MOE), well known for its antioxidant and anti-inflammatory properties, in the spared nerve injury (SNI) model. The molecular mechanisms and efficacy toward neuroinflammation were investigated in spinal cord samples from SNI mice and LPS-stimulated BV2 microglia cells. MOE and HNK showed antioxidant activity. MOE (30 mg/kg p.o.) produced an antiallodynic effect in SNI mice in the absence of locomotor impairment, reduced spinal p-p38, p-JNK1, iNOS, p-p65, IL-1ß, and Nrf2 overexpression, increased IL-10 and MBP levels and attenuated the Notch signaling pathway by reducing Jagged1 and NEXT. These effects were prevented by the CB1 antagonist AM251. HNK reduced the proinflammatory response of LPS-stimulated BV2 and reduced Jagged1 overexpression. MOE and HNK, by modulating oxidative and proinflammatory responses, might represent interesting candidates for NP management.
Collapse
Affiliation(s)
| | - Nicoletta Galeotti
- Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy;
| |
Collapse
|
|
12
|
Izadi M, Javanbakht M, Sarafzadeh A, Einollahi B, Futuhi F, Vahedi Z, Zhao S, Jonaidi-Jafari N, Hosseini MS, Nejad JH, Naeimi E, Saadat SH, Ghaleh HEG, Fazel M, Einollahi Z, Cegolon L. Efficacy of ozone therapy on visual evoked potentials in diabetic patients. Diabetol Metab Syndr 2023; 15:140. [PMID: 37365632 PMCID: PMC10291751 DOI: 10.1186/s13098-023-01114-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 06/16/2023] [Indexed: 06/28/2023] Open
Abstract
BACKGROUND The involvement of the central nervous system is a frequent yet underestimated complication of diabetes mellitus. Visual evoked potentials (VEP) are a simple, sensitive, and noninvasive method for detecting early alterations in central optic pathways. The objective of this paralleled randomized controlled trial was to evaluate the impact of ozone therapy on visual pathways in diabetic patients. METHODS Sixty patients with type 2 diabetes visiting clinics of Baqiyatallah university in Tehran (Iran) hospital were randomly assigned to two experimental groups: Group 1 (N = 30) undergoing a cycle of 20 sessions of systemic oxygen-ozone therapy in addition to standard therapy for metabolic control; Group 2 (N = 30)-serving as control-receiving only standard therapy against diabetes. The primary study endpoints were two VEP parameters; P100 wave latency and P100 amplitude at 3 months. Moreover, HbA1c levels were measured before the start of treatment and three months later as secondary study endpoint. RESULTS All 60 patients completed the clinical trial. P100 latency significantly reduced at 3 months since baseline. No correlation was found between repeated measures of P100 wave latency and HbA1c (Pearson's r = 0.169, p = 0.291). There was no significant difference between baseline values and repeated measures of P100 wave amplitude over time in either group. No adverse effects were recorded. CONCLUSIONS Ozone therapy improved the conduction of impulses in optic pathways of diabetic patients. The improved glycemic control following ozone therpay may not fully explain the reduction of P100 wave latency though; other mechanistic effects of ozone may be involved.
Collapse
Affiliation(s)
- Morteza Izadi
- Health Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mohammad Javanbakht
- Nephrology and Urology Research Center, Clinical Science Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Ali Sarafzadeh
- Department of Biostatistics, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Behzad Einollahi
- Nephrology and Urology Research Center, Clinical Science Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Farzaneh Futuhi
- Nephrology Department, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Vahedi
- Department of Pediatrics, School of Medicine, Hazrat-E Ali. Asghar Pediatrics Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Shi Zhao
- JC School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, China
| | | | - Mahboobeh Sadat Hosseini
- Health Research Center, Lifestyle Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Javad Hosseini Nejad
- Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Effat Naeimi
- Endocrinology and Metabolism Department, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Seyed Hassan Saadat
- Behavioral Sciences Research Center, Lifestyle Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | | | | | - Zahra Einollahi
- Nephrology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Luca Cegolon
- Department of Medical, Surgical & Health Sciences, University of Trieste, Trieste, Italy
- Occupational Medicine Unit, University Health Agency Giuliano-ISontina (ASUGI), Trieste, Italy
| |
Collapse
|
|
13
|
Alkholifi FK, Aodah AH, Foudah AI, Alam A. Exploring the Therapeutic Potential of Berberine and Tocopherol in Managing Diabetic Neuropathy: A Comprehensive Approach towards Alleviating Chronic Neuropathic Pain. Biomedicines 2023; 11:1726. [PMID: 37371821 DOI: 10.3390/biomedicines11061726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 06/12/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
Diabetic neuropathy (DN) causes sensory dysfunction, such as numbness, tingling, or burning sensations. Traditional medication may not ease pain and discomfort, but natural remedies such as Berberine (BR) and vitamin E or Tocopherol (TOC) have therapeutic potential to reduce inflammation while improving nerve function. Novel substances offer a more potent alternative method for managing severe chronic neuropathic pain that does not react to standard drug therapy by targeting various pathways that regulate it. Rats with diabetic control received oral doses of BR + TOC that showed significant changes in serum insulin levels compared to DN controls after 90 days, suggesting a decrease in sensitivity to painful stimuli partly by modulating the oxidative stress of the inflammatory pathway such as TNF-α suppression or stimulation of TNF-α depending on the amount of dose consumed by them. NF-kB also played its role here. Administering doses of BR and TOC reduced heightened levels of NF-kB and AGEs, effectively counteracting inflammation-targeted key factors in diabetes, promising possibilities for the benefits of these molecules revealed through in vivo investigation. In summary, treating neuropathy pain with a more comprehensive and organic approach can involve harnessing the powerful capabilities of BR and TOC. These compounds have been found to not only considerably decrease inflammation but also provide effective nerve protection while enhancing overall nerve function. With their multifunctional impacts on various neuropathic pain pathways in the body, these naturally occurring substances offer an exciting possibility for those who encounter high levels of neuropathic distress that do not respond well to conventional medication-centred therapies.
Collapse
Affiliation(s)
- Faisal K Alkholifi
- Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Alhussain H Aodah
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Ahmed I Foudah
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Aftab Alam
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| |
Collapse
|
|
14
|
Kong Y, Shi W, Zheng L, Zhang D, Jiang X, Liu B, Xue W, Kuss M, Li Y, Sorgen PL, Duan B. In situ delivery of a curcumin-loaded dynamic hydrogel for the treatment of chronic peripheral neuropathy. J Control Release 2023; 357:319-332. [PMID: 37028453 PMCID: PMC10164707 DOI: 10.1016/j.jconrel.2023.04.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 03/28/2023] [Accepted: 04/02/2023] [Indexed: 04/09/2023]
Abstract
Patients with peripheral nerve injuries would highly likely suffer from chronic neuropathic pain even after surgical intervention. The primary reasons for this involve sustained neuroinflammatory and dysfunctional changes in the nervous system after the nerve injury. We previously reported an injectable boronic ester-based hydrogel with inherent antioxidative and nerve protective properties. Herein, we first explored the anti-neuroinflammatory effects of Curcumin on primary sensory neurons and activated macrophages in vitro. Next, we incorporated thiolated Curcumin-Pluronic F-127 micelles (Cur-M) into our boronic ester-based hydrogel to develop an injectable hydrogel that serves as sustained curcumin release system (Gel-Cur-M). By orthotopically injecting the Gel-Cur-M to sciatic nerves of mice with chronic constriction injuries, we found that the bioactive components could remain on the nerves for at least 21 days. In addition, the Gel-Cur-M exhibited superior functions compared to Gel and Cur-M alone, which includes ameliorating hyperalgesia while simultaneously improving locomotor and muscular functions after the nerve injury. This could stem from in situ anti-inflammation, antioxidation, and nerve protection. Furthermore, the Gel-Cur-M also showed extended beneficial effects for preventing the overexpression of TRPV1 as well as microglial activation in the lumbar dorsal root ganglion and spinal cord, respectively, which also contributed to its analgesic effects. The underlying mechanism may involve the suppression of CC chemokine ligand-2 and colony-stimulating factor-1 in the injured sensory neurons. Overall, this study suggests that orthotopic injection of the Gel-Cur-M is a promising therapeutic strategy that especially benefits patients with peripheral neuropathy who require surgical interventions.
Collapse
Affiliation(s)
- Yunfan Kong
- Mary & Dick Holland Regenerative Medicine Program University of Nebraska Medical Center, Omaha, NE 68198, USA; Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Wen Shi
- Mary & Dick Holland Regenerative Medicine Program University of Nebraska Medical Center, Omaha, NE 68198, USA; Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Li Zheng
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Dongze Zhang
- Department of Emergency Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Xiping Jiang
- Mary & Dick Holland Regenerative Medicine Program University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Bo Liu
- Mary & Dick Holland Regenerative Medicine Program University of Nebraska Medical Center, Omaha, NE 68198, USA; Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Wen Xue
- Mary & Dick Holland Regenerative Medicine Program University of Nebraska Medical Center, Omaha, NE 68198, USA; Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Mitchell Kuss
- Mary & Dick Holland Regenerative Medicine Program University of Nebraska Medical Center, Omaha, NE 68198, USA; Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Yulong Li
- Department of Emergency Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Paul L Sorgen
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Bin Duan
- Mary & Dick Holland Regenerative Medicine Program University of Nebraska Medical Center, Omaha, NE 68198, USA; Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA; Department of Surgery, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA; Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
| |
Collapse
|
|
15
|
Cross W, Srivastava S. A Double-Blind, Randomized, Placebo-Controlled Study to Assess the Efficacy of a Nerve Support Formula on Neuropathic Pain in Individuals Suffering from Type II Diabetes Mellitus. J Pain Res 2023; 16:1115-1126. [PMID: 37020664 PMCID: PMC10069439 DOI: 10.2147/jpr.s397777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 03/01/2023] [Indexed: 03/31/2023] Open
Abstract
Background The primary objective of the present study was to evaluate the effects of a Nerve Support Formula NeuropAWAY® on diabetic neuropathic pain. Methods This double-blind, placebo-controlled, randomized trial was conducted between August 2020 and February 2021. Patients aged ≥40 and ≤65 years with a history of type 2 diabetes (T2D) with a confirmed diagnosis of diabetic neuropathic pain were included in the study. The primary efficacy endpoint was to assess the effect of the 42 days administration of the Nerve Support Formula on the neuropathic pain as assessed by the 11 point Pain Intensity Numeric Rating Scale (PI-NRS). The secondary objectives were to assess the effect on plasma vitamin B12 levels, nerve conduction velocity, blood flow velocity, Brief Pain Inventory, Neuropathy Total Symptom Score, and Insomnia Severity Index. Results The enrolled study population (n=59) was randomized in two study groups; the Investigational Product (IP) group - Nerve Support Formula (n=27) and placebo group (n=32). The mean age of these participants was 52.63 and 53.72 for IP and placebo group, respectively. The mean (SD) HbA1c levels for IP and placebo group were 8.37 (0.85) and 8.16 (0.86), respectively. By the end of the study (Day 42) the decrease in PI-NRS scores for the IP group was maximal (↓61.32%) and highly significant (p<0.001) in comparison to the placebo group (↑2.47%). Significant improvements (p<0.05) were also noted in the secondary efficacy variables after 42 days of IP intake. Conclusion The formula was found to be significantly effective as compared to placebo in reducing pain and other sensory symptoms related to the diabetic peripheral neuropathy.
Collapse
|
|
16
|
Zhou L, Yang H, Wang J, Liu Y, Xu Y, Xu H, Feng Y, Ge W. The Therapeutic Potential of Antioxidants in Chemotherapy-Induced Peripheral Neuropathy: Evidence from Preclinical and Clinical Studies. Neurotherapeutics 2023; 20:339-358. [PMID: 36735180 PMCID: PMC10121987 DOI: 10.1007/s13311-023-01346-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/17/2023] [Indexed: 02/04/2023] Open
Abstract
As cancer therapies advance and patient survival improves, there has been growing concern about the long-term adverse effects that patients may experience following treatment, and concerns have been raised about such persistent, progressive, and often irreversible adverse effects. Chemotherapy is a potentially life-extending treatment, and chemotherapy-induced peripheral neuropathy (CIPN) is one of its most common long-term toxicities. At present, strategies for the prevention and treatment of CIPN are still an open problem faced by medicine, and there has been a large amount of previous evidence that oxidative damage is involved in the process of CIPN. In this review, we focus on the lines of defense involving antioxidants that exert the effect of inhibiting CIPN. We also provide an update on the targets and clinical prospects of different antioxidants (melatonin, N-acetylcysteine, vitamins, α-lipoic acid, mineral elements, phytochemicals, nutritional antioxidants, cytoprotectants and synthetic compounds) in the treatment of CIPN with the help of preclinical and clinical studies, emphasizing the great potential of antioxidants as adjuvant strategies to mitigate CIPN.
Collapse
Affiliation(s)
- Lin Zhou
- Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, #321 Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Hui Yang
- Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, #321 Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Jing Wang
- Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, #321 Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Yunxing Liu
- Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, #321 Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Yinqiu Xu
- Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, #321 Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Hang Xu
- Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, #321 Zhongshan Road, Nanjing, 210008, Jiangsu, China
| | - Yong Feng
- Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, #42 Baizi Ting Road, Nanjing, 210009, Jiangsu, China.
| | - Weihong Ge
- Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, #321 Zhongshan Road, Nanjing, 210008, Jiangsu, China.
| |
Collapse
|
|
17
|
Lee Y, Bae CS, Ahn T. Chlorogenic acid attenuates pro-inflammatory response in the blood of streptozotocin-induced diabetic rats. Lab Anim Res 2022; 38:37. [PMID: 36461118 PMCID: PMC9719206 DOI: 10.1186/s42826-022-00148-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 11/16/2022] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND Chlorogenic acid (CGA) has been shown to reduce pro-inflammation by scavenging reactive oxygen species (ROS) and reactive nitrogen species. In this study, the anti-inflammatory effect of CGA was expanded to streptozotocin (STZ)-induced diabetic rats. The inter-relationships among oxidative stress, pro-inflammation, and cytochrome P450 (CYP) 1A enzymes were also investigated in peripheral blood mononuclear cells (PBMC) of STZ-diabetic rats. RESULTS The levels of pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor-alpha, increased by approximately 3.4- and 2.9-fold, respectively, and the albumin concentration decreased in the serum of STZ-induced diabetic rats compared to normal rats. The C-reactive protein (CRP) values also increased by about 3.8-fold higher, indicating that STZ induced an inflammation in the blood of STZ-diabetic rats. The expression levels and catalytic activities of CYP1A enzymes were elevated by approximately 2.2-2.5- and 4.3-6.7-fold, respectively, in the PBMC of STZ-treated rats. A decrease in the amount of PBMC-bound albumin was also observed. In contrast, the levels of cytokines and CRP in serum and the activities of CYP1A enzymes in PBMC were significantly reduced in CGA-treated diabetic rats in a CGA concentration-dependent manner. In addition, STZ-mediated elevation of ROS in serum and PBMC was decreased by the CGA administration. However, the CGA treatment did not change the enhanced blood glucose level and expression of CYP1A enzymes by STZ. STZ-mediated decrease in the levels of serum and PBMC-bound albumin was not also restored by the CGA administration. CONCLUSIONS These results suggest that CGA could be used to treat type 1 diabetes-induced inflammation.
Collapse
Affiliation(s)
- Youngchan Lee
- College of Veterinary Medicine, Chonnam National University, 77 Yongbong-Ro, Buk-Gu, Gwangju, 61186, Republic of Korea
| | - Chun-Sik Bae
- College of Veterinary Medicine, Chonnam National University, 77 Yongbong-Ro, Buk-Gu, Gwangju, 61186, Republic of Korea
| | - Taeho Ahn
- College of Veterinary Medicine, Chonnam National University, 77 Yongbong-Ro, Buk-Gu, Gwangju, 61186, Republic of Korea.
| |
Collapse
|
|
18
|
Shaforostova EA, Gureev AP, Volodina DE, Popov VN. Neuroprotective effect of mildronate and L-carnitine on the cognitive parameters of aged mice and mice with LPS-induced inflammation. Metab Brain Dis 2022; 37:2497-2510. [PMID: 35881298 DOI: 10.1007/s11011-022-01047-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Accepted: 07/03/2022] [Indexed: 11/27/2022]
Abstract
Mildronate (MD) is a cardioprotective drug used for the treatment of cardiovascular diseases by switching metabolism from the fatty acids to glucose oxidation. This effect is achieved via inhibition of synthesis of L-carnitine (L-car), a common supplement, which is used for improving of fatty acid metabolism. Both MD and L-car have similar neuroprotective effect. Our goal was to investigate the effect of two drugs on the cognitive parameters of mice under different conditions (aging and lipopolysaccharide (LPS)-induced inflammation). We showed that L-car partly improved the memory and decreased the extent of mtDNA damage in the hippocampus of mice with the LPS-induced inflammation. L-car induced mitochondrial biogenesis and mitophagy in the Nrf2-dependent manner. Both MD and L-car upregulated expression of genes involved in the mitochondrial quality control. In 15-month-old mice, MD improved long-term and short-term memory, reduced the extent of mtDNA damage, and decreased the concentration of diene conjugates in the hippocampus in the Nrf2-independent manner. L-car as a Nrf2 activator had a better neuroprotective effect by normalizing mitochondrial quality control in the reversible cognitive impairment caused by the LPS-induced inflammation, while MD had a better neuroprotective effect in the irreversible cognitive impairment in aged mice, possibly due to a deeper restructuring of metabolism and reduction of oxidative stress.
Collapse
Affiliation(s)
- Ekaterina A Shaforostova
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, Voronezh, Russia.
| | - Artem P Gureev
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, Voronezh, Russia
- Voronezh State University of Engineering Technology, Voronezh, Russia
| | - Daria E Volodina
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, Voronezh, Russia
| | - Vasily N Popov
- Department of Genetics, Cytology and Bioengineering, Voronezh State University, Voronezh, Russia
- Voronezh State University of Engineering Technology, Voronezh, Russia
| |
Collapse
|
|
19
|
Shen CL, Castro L, Fang CY, Castro M, Sherali S, White S, Wang R, Neugebauer V. Bioactive compounds for neuropathic pain: An update on preclinical studies and future perspectives. J Nutr Biochem 2022; 104:108979. [PMID: 35245654 DOI: 10.1016/j.jnutbio.2022.108979] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 01/21/2022] [Accepted: 02/21/2022] [Indexed: 12/19/2022]
Abstract
Among different types of chronic pain, neuropathic pain (NP), arising from damage to the nervous system, including peripheral fibers and central neurons, is notoriously difficult to treat and affects 7-10% of the general population. Currently available treatment options for NP are limited and opioid analgesics have severe side effects and can result in opioid use disorder. Recent studies have exhibited the role of dietary bioactive compounds in the mitigation of NP. Here, we assessed the effects of commonly consumed bioactive compounds (ginger, curcumin, omega-3 polyunsaturated fatty acids, epigallocatechin gallate, resveratrol, soy isoflavones, lycopene, and naringin) on NP and NP-related neuroinflammation. Cellular studies demonstrated that these bioactive compounds reduce inflammation via suppression of NF-κB and MAPK signaling pathways that regulate apoptosis/cell survival, antioxidant, and anti-inflammatory responses. Animal studies strongly suggest that these regularly consumed bioactive compounds have a pronounced anti-NP effect as shown by decreased mechanical allodynia, mechanical hyperalgesia, thermal hyperalgesia, and cold hyperalgesia. The proposed molecular mechanisms include (1) the enhancement of neuron survival, (2) the reduction of neuronal hyperexcitability by activation of antinociceptive cannabinoid 1 receptors and opioid receptors, (3) the suppression of sodium channel current, and (4) enhancing a potassium outward current in NP-affected animals, triggering a cascade of chemical changes within, and between neurons for pain relief. Human studies administered in this area have been limited. Future randomized controlled trials are warranted to confirm the findings of preclinical efficacies using bioactive compounds in patients with NP.
Collapse
Affiliation(s)
- Chwan-Li Shen
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA; Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, Texas, USA; Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
| | - Luis Castro
- School of Medicine, Texas Tech University Health Sciences, Lubbock, Texas, USA
| | - Chih-Yu Fang
- School of Medicine, Texas Tech University Health Sciences, Lubbock, Texas, USA
| | - Maribel Castro
- School of Medicine, Texas Tech University Health Sciences, Lubbock, Texas, USA
| | - Samir Sherali
- School of Medicine, Texas Tech University Health Sciences, Lubbock, Texas, USA
| | - Steely White
- Department of Microbiology, Texas Tech University, Lubbock, Texas, USA
| | - Rui Wang
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Volker Neugebauer
- Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, Texas, USA; Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, Texas, USA; Department of Pharmacology & Neuroscience, Texas Tech University Health Sciences Center, Lubbock, Texas, USA; Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| |
Collapse
|
|
20
|
Bae CS, Ahn T. Albumin infusion ameliorates liver injury in streptozotocin-induced diabetic rats. VET MED-CZECH 2022; 67:245-256. [PMID: 39170903 PMCID: PMC11334145 DOI: 10.17221/14/2021-vetmed] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 12/29/2021] [Indexed: 08/23/2024] Open
Abstract
We investigated the effect of an albumin infusion on the enzyme activity, expression level of cytochrome P450 2E1 (CYP2E1), and oxidative stress in the serum and liver of streptozotocin (STZ)-induced diabetic rats. The STZ treatment enhanced the alanine aminotransferase and aspartate aminotransferase activities in the rat serum compared with those in the untreated rats. Treatment with STZ elevated the expression and catalytic activity of CYP2E1, and the oxidative stress, and decreased the reducing potentials in the liver, suggesting the possibility of diabetes-induced liver injury. Moreover, the antioxidant activity of the serum albumin decreased in the diabetic rats. In contrast, the administration of purified albumin from the intact rats to the diabetic rats restored these deleterious liver indices in an albumin concentration-dependent manner. These results suggest that an exogenous albumin infusion alleviates liver damage induced by type 1 diabetes.
Collapse
Affiliation(s)
- Chun-Sik Bae
- College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea
| | - Taeho Ahn
- College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea
| |
Collapse
|
|
21
|
Durán AM, Beeson WL, Firek A, Cordero-MacIntyre Z, De León M. Dietary Omega-3 Polyunsaturated Fatty-Acid Supplementation Upregulates Protective Cellular Pathways in Patients with Type 2 Diabetes Exhibiting Improvement in Painful Diabetic Neuropathy. Nutrients 2022; 14:nu14040761. [PMID: 35215418 PMCID: PMC8876723 DOI: 10.3390/nu14040761] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 02/04/2022] [Accepted: 02/08/2022] [Indexed: 12/12/2022] Open
Abstract
Background: Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. For instance, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms, but cellular mechanisms responsible for this therapeutic effect are not well understood. The objective of this study is to identify distinct cellular pathways elicited by dietary omega-3 PUFA supplementation in patients with type 2 diabetes mellitus (T2DM) affected by pDN. Methods: Forty volunteers diagnosed with type 2 diabetes were enrolled in the “En Balance-PLUS” diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data were analyzed using random forest, hierarchical clustering, ingenuity pathway analysis, and metabolic pathway mapping. Results: The data show that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (−11%), glycine (+11%), and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253%) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species (p = 4.38 × 10−4, z-score = −1.96), peroxidation of lipids (p = 2.24 × 10−5, z-score = −1.944), Ca2+ transport (p = 1.55 × 10−4, z-score = −1.969), excitation of neurons (p = 1.07 ×10−4, z-score = −1.091), and concentration of glutathione (p = 3.06 × 10−4, z-score = 1.974). Conclusion: The reduction of pro-inflammatory and oxidative stress pathways following dietary omega-3 PUFA supplementation is consistent with the promising role of these fatty acids in reducing adverse symptoms associated with neuroinflammatory diseases and painful neuropathy.
Collapse
Affiliation(s)
- Alfonso M. Durán
- Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA; (A.M.D.); (W.L.B.); (Z.C.-M.)
| | - W. Lawrence Beeson
- Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA; (A.M.D.); (W.L.B.); (Z.C.-M.)
- Center for Nutrition, Healthy Lifestyle and Disease Prevention, School of Public Health, Loma Linda University, Loma Linda, CA 92350, USA
| | - Anthony Firek
- Comparative Effectiveness and Clinical Outcomes Research Center, Riverside University Health System Medical Center, Moreno Valley, CA 92555, USA;
| | - Zaida Cordero-MacIntyre
- Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA; (A.M.D.); (W.L.B.); (Z.C.-M.)
- Center for Nutrition, Healthy Lifestyle and Disease Prevention, School of Public Health, Loma Linda University, Loma Linda, CA 92350, USA
| | - Marino De León
- Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA; (A.M.D.); (W.L.B.); (Z.C.-M.)
- Correspondence: ; Tel.: +1-909-558-9474
| |
Collapse
|
|
22
|
Sloan G, Alam U, Selvarajah D, Tesfaye S. The Treatment of Painful Diabetic Neuropathy. Curr Diabetes Rev 2022; 18:e070721194556. [PMID: 34238163 DOI: 10.2174/1573399817666210707112413] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 02/18/2021] [Accepted: 03/08/2021] [Indexed: 11/22/2022]
Abstract
Painful diabetic peripheral neuropathy (painful-DPN) is a highly prevalent and disabling condition, affecting up to one-third of patients with diabetes. This condition can have a profound impact resulting in a poor quality of life, disruption of employment, impaired sleep, and poor mental health with an excess of depression and anxiety. The management of painful-DPN poses a great challenge. Unfortunately, currently there are no Food and Drug Administration (USA) approved disease-modifying treatments for diabetic peripheral neuropathy (DPN) as trials of putative pathogenetic treatments have failed at phase 3 clinical trial stage. Therefore, the focus of managing painful- DPN other than improving glycaemic control and cardiovascular risk factor modification is treating symptoms. The recommended treatments based on expert international consensus for painful- DPN have remained essentially unchanged for the last decade. Both the serotonin re-uptake inhibitor (SNRI) duloxetine and α2δ ligand pregabalin have the most robust evidence for treating painful-DPN. The weak opioids (e.g. tapentadol and tramadol, both of which have an SNRI effect), tricyclic antidepressants such as amitriptyline and α2δ ligand gabapentin are also widely recommended and prescribed agents. Opioids (except tramadol and tapentadol), should be prescribed with caution in view of the lack of definitive data surrounding efficacy, concerns surrounding addiction and adverse events. Recently, emerging therapies have gained local licenses, including the α2δ ligand mirogabalin (Japan) and the high dose 8% capsaicin patch (FDA and Europe). The management of refractory painful-DPN is difficult; specialist pain services may offer off-label therapies (e.g. botulinum toxin, intravenous lidocaine and spinal cord stimulation), although there is limited clinical trial evidence supporting their use. Additionally, despite combination therapy being commonly used clinically, there is little evidence supporting this practise. There is a need for further clinical trials to assess novel therapeutic agents, optimal combination therapy and existing agents to determine which are the most effective for the treatment of painful-DPN. This article reviews the evidence for the treatment of painful-DPN, including emerging treatment strategies such as novel compounds and stratification of patients according to individual characteristics (e.g. pain phenotype, neuroimaging and genotype) to improve treatment responses.
Collapse
Affiliation(s)
- Gordon Sloan
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, NHS Foundation Trust, Sheffield, UK
| | - Uazman Alam
- Department of Cardiovascular and Metabolic Medicine and the Pain Research Institute, Institute of Life Course and Medical Sciences, University of Liverpool, and Liverpool University Hospital, NHS Foundation Trust, Liverpool, UK
- Division of Diabetes, Endocrinology and Gastroenterology, Institute of Human Development, University of Manchester, Manchester, UK
| | - Dinesh Selvarajah
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, NHS Foundation Trust, Sheffield, UK
- Department of Oncology and Human Metabolism, University of Sheffield, Sheffield, UK
| | - Solomon Tesfaye
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, NHS Foundation Trust, Sheffield, UK
| |
Collapse
|
|
23
|
Méndez-Morales S, Pérez-De Marco J, Rodríguez-Cortés O, Flores-Mejía R, Martínez-Venegas M, Sánchez-Vera Y, Tamay-Cach F, Lomeli-Gonzaléz J, Emilio Reyes A, Lehman-Mendoza R, Martínez-Arredondo H, Vazquez-Dávila R, Torres-Roldan J, Correa-Basurto J, Arellano-Mendoza M. Diabetic neuropathy: Molecular approach a treatment opportunity. Vascul Pharmacol 2022; 143:106954. [PMID: 35063655 DOI: 10.1016/j.vph.2022.106954] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 01/11/2022] [Accepted: 01/13/2022] [Indexed: 12/15/2022]
|
|
24
|
Neuromuscular Manifestations of Acquired Metabolic, Endocrine, and Nutritional Disorders. Neuromuscul Disord 2022. [DOI: 10.1016/b978-0-323-71317-7.00021-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
|
|
25
|
Neerati P, Prathapagiri H. Alpha lipoic acid attenuated neuropathic pain induced by chronic constriction Injury of sciatic nerve in rats. CLINICAL PHYTOSCIENCE 2021. [DOI: 10.1186/s40816-021-00263-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Abstract
Background
Chronic neuropathic pain syndrome is associated with impaired quality of life and is poorly manageable. Alpha lipoic acid (ALA) is a powerful antioxidant and showed its effectiveness on diabetic neuropathy and other acute peripheral nerve injuries but it was not evaluated in the chronic neuropathic pain, chronic constriction injury (CCI) in rat model by using duloxetine (DLX) as standard.
Methodology
The main objective of the study was to expedite ALA effect on chronic peripheral neuropathy induced by CCI of sciatic nerve in rats. In this study, male Wister rats were randomly divided into six groups (n = 8) including, normal saline, sham operated, surgery control, DLX 30mg/kg treated, ALA treated 25mg/kg, and ALA+DLX. The CCI of sciatic nerve was conducted on all animals except normal saline group and studied for 21 days (i.e. 14 days treatment period & 7 days treatment free period) by using different behavioral, biochemical and, histopathology studies.
Results
ALA showed minor but significant decrease of thermal hyperalgesia, cold allodynia, malondialdehyde (MDA), total protein, lipid peroxidation, and nitric oxide levels and significant increase of motor coordination, glutathione level and decreased axonal degeneration significantly. These effects sustained even during treatment free period. ALA enhanced the effect of DLX when given in combination by showing sustained effect. In conclusion, ALA acted as potent antioxidant may be this activity is responsible for the potent neuroprotective effect.
Conclusion
Hence, ALA attenuated the nueroinflammation mediated by chronic peripheral neuropathy. Further studies are warranted with ALA to develop as a clinically relevant therapeutic agent for the treatment of neuropathic pain.
Collapse
|
|
26
|
Sathishkumar P, Mohan K, Meena RAA, Balasubramanian M, Chitra L, Ganesan AR, Palvannan T, Brar SK, Gu FL. Hazardous impact of diclofenac on mammalian system: Mitigation strategy through green remediation approach. JOURNAL OF HAZARDOUS MATERIALS 2021; 419:126135. [PMID: 34157463 DOI: 10.1016/j.jhazmat.2021.126135] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 04/24/2021] [Accepted: 05/12/2021] [Indexed: 05/22/2023]
Abstract
Diclofenac is an anti-inflammatory drug used as an analgesic. It is often detected in various environmental sources around the world and is considered as one of the emerging contaminants (ECs). This paper reviews the distribution of diclofenac at high concentrations in diverse environments and its adverse ecological impact. Recent studies observed strong evidence of the hazardous effect of diclofenac on mammals, including humans. Diclofenac could cause gastrointestinal complications, neurotoxicity, cardiotoxicity, hepatotoxicity, nephrotoxicity, hematotoxicity, genotoxicity, teratogenicity, bone fractures, and skin allergy in mammals even at a low concentration. Collectively, this comprehensive review relates the mode of toxicity, level of exposure, and route of administration as a unique approach for addressing the destructive consequence of diclofenac in mammalian systems. Finally, the mitigation strategy to eradicate the diclofenac toxicity through green remediation is critically discussed. This review will undoubtedly shed light on the toxic effects of pseudo-persistent diclofenac on mammals as well as frame stringent guidelines against its common usage.
Collapse
Affiliation(s)
- Palanivel Sathishkumar
- Key Laboratory of Theoretical Chemistry of Environment, Ministry of Education; School of Chemistry, South China Normal University, Guangzhou 510006, PR China
| | - Kannan Mohan
- PG and Research Department of Zoology, Sri Vasavi College, Erode, Tamil Nadu 638 316, India
| | | | - Murugesan Balasubramanian
- Department of Biotechnology, K.S. Rangasamy College of Technology, Tiruchengode 637 215, Tamil Nadu, India
| | - Loganathan Chitra
- Department of Biochemistry, Periyar University, Salem 636 011, Tamil Nadu, India
| | - Abirami Ramu Ganesan
- Group of Fermentation and Distillation, Laimburg Research Center, Vadena (BZ), Italy
| | | | - Satinder Kaur Brar
- Department of Civil Engineering, Lassonde School of Engineering, York University, North York, Toronto, Ontario M3J 1P3, Canada
| | - Feng Long Gu
- Key Laboratory of Theoretical Chemistry of Environment, Ministry of Education; School of Chemistry, South China Normal University, Guangzhou 510006, PR China.
| |
Collapse
|
|
27
|
Sloan G, Selvarajah D, Tesfaye S. Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy. Nat Rev Endocrinol 2021; 17:400-420. [PMID: 34050323 DOI: 10.1038/s41574-021-00496-z] [Citation(s) in RCA: 231] [Impact Index Per Article: 57.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/15/2021] [Indexed: 02/08/2023]
Abstract
Diabetic sensorimotor peripheral neuropathy (DSPN) is a serious complication of diabetes mellitus and is associated with increased mortality, lower-limb amputations and distressing painful neuropathic symptoms (painful DSPN). Our understanding of the pathophysiology of the disease has largely been derived from animal models, which have identified key potential mechanisms. However, effective therapies in preclinical models have not translated into clinical trials and we have no universally accepted disease-modifying treatments. Moreover, the condition is generally diagnosed late when irreversible nerve damage has already taken place. Innovative point-of-care devices have great potential to enable the early diagnosis of DSPN when the condition might be more amenable to treatment. The management of painful DSPN remains less than optimal; however, studies suggest that a mechanism-based approach might offer an enhanced benefit in certain pain phenotypes. The management of patients with DSPN involves the control of individualized cardiometabolic targets, a multidisciplinary approach aimed at the prevention and management of foot complications, and the timely diagnosis and management of neuropathic pain. Here, we discuss the latest advances in the mechanisms of DSPN and painful DSPN, originating both from the periphery and the central nervous system, as well as the emerging diagnostics and treatments.
Collapse
Affiliation(s)
- Gordon Sloan
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Dinesh Selvarajah
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Department of Oncology and Human Metabolism, University of Sheffield, Sheffield, UK
| | - Solomon Tesfaye
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
| |
Collapse
|
|
28
|
Kale MB, Bajaj K, Umare M, Wankhede NL, Taksande BG, Umekar MJ, Upaganlawar A. Exercise and Nutraceuticals: Eminent approach for Diabetic Neuropathy. Curr Mol Pharmacol 2021; 15:108-128. [PMID: 34191703 DOI: 10.2174/1874467214666210629123010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 02/28/2021] [Accepted: 03/05/2021] [Indexed: 11/22/2022]
Abstract
Diabetic neuropathy is an incapacitating chronic pathological condition that encompasses a large group of diseases and manifestations of nerve damage. It affects approximately 50% of patients with diabetes mellitus. Autonomic, sensory, and motor neurons are affected. Disabilities are severe, along with poor recovery and diverse pathophysiology. Physical exercise and herbal-based therapies have the potential to decrease the disabilities associated with diabetic neuropathy. Aerobic exercises like walking, weight lifting, the use of nutraceuticals and herbal extracts are found to be effective. Literature from the public domain was studied emphasizing various beneficial effects of different exercises, use of herbal and nutraceuticals for their therapeutic action in diabetic neuropathy. Routine exercises and administration of herbal and nutraceuticals, either the extract of plant material containing the active phytoconstituent or isolated phytoconstituent at safe concentration, have been shown to have promising positive action in the treatment of diabetic neuropathy. Exercise has shown promising effects on vascular and neuronal health and has proven to be well effective in the treatment as well as prevention of diabetic neuropathy by various novel mechanisms, including herbal and nutraceuticals therapy is also beneficial for the condition. They primarily show the anti-oxidant effect, secretagogue, anti-inflammatory, analgesic, and neuroprotective action. Severe adverse events are rare with these therapies. The current review investigates the benefits of exercise and nutraceutical therapies in the treatment of diabetic neuropathy.
Collapse
Affiliation(s)
- Mayur Bhimrao Kale
- Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India
| | - Komal Bajaj
- Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India
| | - Mohit Umare
- Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India
| | - Nitu L Wankhede
- Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India
| | | | - Milind Janrao Umekar
- Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India
| | - Aman Upaganlawar
- SNJB's Shriman Sureshdada Jain College of Pharmacy, Neminagar, Chandwad-42310, Nasik, Maharashtra, India
| |
Collapse
|
|
29
|
Chen L, Chen Z, Xu Z, Feng W, Yang X, Qi Z. Polydatin protects Schwann cells from methylglyoxal induced cytotoxicity and promotes crushed sciatic nerves regeneration of diabetic rats. Phytother Res 2021; 35:4592-4604. [PMID: 34089208 DOI: 10.1002/ptr.7177] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 03/25/2021] [Accepted: 05/07/2021] [Indexed: 01/03/2023]
Abstract
Oxidative stress plays the main role in the pathogenesis of diabetes mellitus and peripheral neuropathy. Polydatin (PD) has been shown to exhibit strong antioxidative and antiinflammatory effects. At present, no research has focused on the possible effects of PD on Schwann cells and impaired peripheral nerves in diabetic models. Here, we used an in vitro Schwann cell damage model induced by methylglyoxal and an in vivo diabetic sciatic nerve crush model to study problems in such an area. In our experiment, we demonstrated that PD potently alleviated the decrease of cellular viability, prevented reactive oxygen species generation, and suppressed mitochondrial depolarization as well as cellular apoptosis in damaged Schwann cells. Moreover, we found that PD could upregulate Nrf2 and Glyoxalase 1 (GLO1) expression and inhibit Keap1 and receptor of AGEs (RAGE) expression of damaged Schwann cells. Finally, our in vivo experiment showed that PD could promote sciatic nerves repair of diabetic rats. Our results revealed that PD exhibited prominent neuroprotective effects on Schwann cells and sciatic nerves in diabetic models. The molecular mechanisms were associated with activating Nfr2 and GLO1 and inhibiting Keap1 and RAGE.
Collapse
Affiliation(s)
- Lulu Chen
- Department No.16 of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zixiang Chen
- Department No.16 of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhuqiu Xu
- Department No.16 of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weifeng Feng
- Department No.16 of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaonan Yang
- Department No.16 of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zuoliang Qi
- Department No.16 of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
30
|
Therapeutic Potential of Polyphenols in the Management of Diabetic Neuropathy. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:9940169. [PMID: 34093722 PMCID: PMC8137294 DOI: 10.1155/2021/9940169] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 04/27/2021] [Indexed: 12/12/2022]
Abstract
Diabetic neuropathy (DN) is a common and serious diabetes-associated complication that primarily takes place because of neuronal dysfunction in patients with diabetes. Use of current therapeutic agents in DN treatment is quite challenging because of their severe adverse effects. Therefore, there is an increased need of identifying new safe and effective therapeutic agents. DN complications are associated with poor glycemic control and metabolic imbalances, primarily oxidative stress (OS) and inflammation. Various mediators and signaling pathways such as glutamate pathway, activation of channels, trophic factors, inflammation, OS, advanced glycation end products, and polyol pathway have a significant contribution to the progression and pathogenesis of DN. It has been indicated that polyphenols have the potential to affect DN pathogenesis and could be used as potential alternative therapy. Several polyphenols including kolaviron, resveratrol, naringenin, quercetin, kaempferol, and curcumin have been administered in patients with DN. Furthermore, chlorogenic acid can provide protection against glutamate neurotoxicity via its hydrolysate, caffeoyl acid group, and caffeic acid through regulating the entry of calcium into neurons. Epigallocatechin-3-gallate treatment can protect motor neurons by regulating the glutamate level. It has been demonstrated that these polyphenols can be promising in combating DN-associated damaging pathways. In this article, we have summarized DN-associated metabolic pathways and clinical manifestations. Finally, we have also focused on the roles of polyphenols in the treatment of DN.
Collapse
|
|
31
|
Mohiuddin M, Pivetta B, Gilron I, Khan JS. Efficacy and Safety of N-acetylcysteine for the Management of Chronic Pain in Adults: A Systematic Review & Meta-analysis. PAIN MEDICINE 2021; 22:2896-2907. [PMID: 33560443 DOI: 10.1093/pm/pnab042] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To assess the efficacy and safety of N-acetylcysteine in the treatment of chronic pain. METHODS A systematic search was carried out until April 2020 for clinical studies of N-acetylcysteine in the management of any persistent or recurrent chronic pain condition for adults ≥ 18 years old. Risk of Bias was assessed using the validated risk of bias tools. When appropriate, a meta-analysis using a random-effects model was performed, with a fixed-effect model for sensitivity analysis. RESULTS Nine studies (n = 863) were included (5 randomized controlled trials [RCTs], 2 open-label non-comparative studies and 2 comparative studies), that evaluated patients with sickle cell disease (3), complex regional pain syndrome (1), pelvic pain/endometriosis (2), rheumatoid arthritis (1), diabetic neuropathy (1), and chronic neuropathic pain (1). In the pooled analysis of 3 RCTs, N-acetylcysteine did not reduce pain intensities (SMD -0.21, 95% CI -0.33 to 0.75, random-effects), improve functional outcomes (SMD 0.21, 95% CI -0.33 to 0.75) or quality of life (SMD 0.60, 95% CI -4.44 to 5.64); however, sensitivity analysis with a fixed effect model demonstrated an effect for pain intensities and function. Due to adverse events being inconsistently reported, no conclusion could be made regarding safety of N-acetylcysteine in chronic pain. CONCLUSIONS While there is some evidence to indicate N-acetylcysteine may provide analgesic efficacy for certain pain conditions, there is insufficient evidence to provide definitive evidence on NAC in chronic pain management. Larger-size RCTs spanning a variety of chronic pain conditions are needed to determine N-acetylcysteine's role, if any, in pain medicine.
Collapse
Affiliation(s)
| | - Bianca Pivetta
- Faculty of Medicine, University of Ottawa, Ottawa, Canada
| | - Ian Gilron
- Department of Anesthesiology and Perioperative Medicine, Kingston General Hospital, Queen's University Kingston, Canada
| | - James S Khan
- Mount Sinai Hospital, Department of Anesthesia and Pain Medicine, University of Toronto, Toronto, Canada
| |
Collapse
|
|
32
|
Islam SMT, Won J, Kim J, Qiao F, Singh AK, Khan M, Singh I. Detoxification of Reactive Aldehydes by Alda-1 Treatment Ameliorates Experimental Autoimmune Encephalomyelitis in Mice. Neuroscience 2021; 458:31-42. [PMID: 33493617 DOI: 10.1016/j.neuroscience.2021.01.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 12/12/2020] [Accepted: 01/12/2021] [Indexed: 11/28/2022]
Abstract
Reactive aldehydes are generated as a toxic end-product of lipid peroxidation under inflammatory oxidative stress condition which is a well-established phenomenon in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Alda-1, a selective agonist of mitochondrial aldehyde dehydrogenase 2 (ALDH2), is known to detoxify the reactive aldehydes. In this study, we investigated the effect of Alda-1 on CNS myelin pathology associated with reactive aldehydes and mitochondrial/peroxisomal dysfunctions in a mouse model of EAE. Daily treatment of EAE mice with Alda-1, starting at the peak of disease, ameliorated the clinical manifestation of disease along with the improvement of motor functions. Accordingly, Alda-1 treatment improved demyelination and neuroaxonal degeneration in EAE mice. EAE mice had increased levels of reactive aldehyde species, such as 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and acrolein (ACL) in the spinal cords and these levels were significantly reduced in Alda-1-treated EAE mice. Furthermore, Alda-1 treatment improved the loss of mitochondrial (OXPHOS) and peroxisomal (PMP70 and catalase) proteins as well as mitochondrial/peroxisomal proliferation factors (PGC-1α and PPARs) in the spinal cords of EAE mice. Taken together, this study demonstrates the therapeutic efficacy of ALDH2-agonist Alda-1 in the abatement of EAE disease through the detoxification of reactive aldehydes, thus suggesting Alda-1 as a potential therapeutic intervention for MS.
Collapse
Affiliation(s)
- S M Touhidul Islam
- Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA
| | - Jeseong Won
- Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA.
| | - Judong Kim
- Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA
| | - Fei Qiao
- Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA
| | - Avtar K Singh
- Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA; Pathology and Laboratory Medicine Service, Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA
| | - Mushfiquddin Khan
- Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA
| | - Inderjit Singh
- Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA; Research Service, Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA.
| |
Collapse
|
|
33
|
Kilic A, Ustunova S, Elibol B, Bulut H, Meral I, Sahin G. Angiotensin IV improves spatial memory in streptozotocin-induced diabetic rats by reducing oxidative stress and altering BDNF levels. Acta Neurobiol Exp (Wars) 2021. [DOI: 10.21307/ane-2021-015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
|
|
34
|
Alharbi AS. Intraoral Lipoma of the Cheek - A Case Report With a One-Year Follow-up and Review of Literature. Cureus 2020; 12:e10537. [PMID: 32968606 PMCID: PMC7505536 DOI: 10.7759/cureus.10537] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Lipomas are mesenchymal adipose tumors that are most common in the human body. However, they are rare in the oral cavity at an occurrence rate of 1% to 4% with male gender predilection. The case presented is of a 37-year-old male who presented with a large painless swelling on the right cheek region. The swelling was present for the past year and had aggravated in the previous one month, causing discomfort during mastication and speech. On clinical examination, a solitary non-fluctuating circumferential swelling on the right cheek was observed. A provisional diagnosis of lipoma was made based on the history and clinical examination, and it was decided to treat by surgical excision. A final diagnosis of lipoma was made based on histopathological analysis of the excised specimen. The patient at a one-week follow-up had recovered from his speech and chewing problems, and no recurrence was reported at a one-year follow-up.
Collapse
Affiliation(s)
- Amal S Alharbi
- Department of Oral and Maxillofacial Surgery, Al Rass General Hospital, Alqassim, SAU
| |
Collapse
|
|
35
|
Sex Difference in Trigeminal Neuropathic Pain Response to Exercise: Role of Oxidative Stress. Pain Res Manag 2020; 2020:3939757. [PMID: 32676135 PMCID: PMC7341438 DOI: 10.1155/2020/3939757] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 05/17/2020] [Accepted: 06/08/2020] [Indexed: 11/17/2022]
Abstract
Aim Orofacial chronic neuropathic pain commonly occurs following trigeminal nerve injuries. We investigated whether swimming exercise can reduce trigeminal neuropathic pain through improving antioxidant capacity. Materials and Methods Twenty-eight Wistar rats of either sex and 180–220 grams were divided into 4 groups as sham, neuropathy, neuropathy + single bout exercise, and neuropathy + 2 weeks of exercise. Trigeminal neuropathy was carried out through chronic constriction injury (CCI) of infraorbital nerve. Protocols of exercise were included a single bout session (45 minutes) and a 2-week (45 minutes/day/6 days a week) swimming exercise. Mechanical allodynia was detected using Von Frey filaments. The activity of the serum antioxidant enzymes glutathione peroxidase and superoxides dismutase was assayed using ELISA kits. Results We found that CCI significantly reduced facial pain threshold in both sexes (P < 0.05). Both swimming exercise protocols significantly reduced mechanical allodynia in female rats compared to the sham group; however, only 2 weeks of exercise were significantly effective in male rats. The activity of antioxidant enzyme glutathione peroxidase significantly (P < 0.05) decreased following CCI in female rats against that in the sham group and 2-week exercise significantly (P < 0.05) increased it toward the control level. The levels of glutathione peroxidase in male rats and superoxidase dismutase in both sexes were not significantly different compared to their sham groups. Conclusion Swimming exercise alleviates trigeminal neuropathic pain in both sexes. Oxidative stress as a possible mechanism was involved in the effect of exercise on female rat trigeminal neuropathy.
Collapse
|
|
36
|
Lu Y, Zhang P, Zhang Q, Yang C, Qian Y, Suo J, Tao X, Zhu J. Duloxetine Attenuates Paclitaxel-Induced Peripheral Nerve Injury by Inhibiting p53-Related Pathways. J Pharmacol Exp Ther 2020; 373:453-462. [PMID: 32238452 DOI: 10.1124/jpet.120.265082] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 03/18/2020] [Indexed: 03/08/2025] Open
Abstract
Paclitaxel (PTX) is an antineoplastic drug extracted from the Taxus species, and peripheral neuropathy is a common side effect. Paclitaxel-induced peripheral neuropathy (PIPN) seriously affects patient quality of life. Currently, the mechanism of PIPN is still unknown, and few treatments are recognized clinically. Duloxetine is recommended as the only potential treatment of chemotherapy-induced peripheral neuropathy (CIPN) by the American Society of Clinical Oncology. However, this guidance lacks a theoretical basis and experimental evidence. Our study suggested that duloxetine could improve PIPN and provide neuroprotection. We explored the potential mechanisms of duloxetine on PIPN. As a result, duloxetine acts by inhibiting poly ADP-ribose polymerase cleavage (PARP) and tumor suppressor gene p53 activation and regulating apoptosis regulator the Bcl2 family to reverse PTX-induced oxidative stress and apoptosis. Taken together, the present study shows that using duloxetine to attenuate PTX-induced peripheral nerve injury and peripheral pain may provide new clinical therapeutic targets for CIPN. SIGNIFICANCE STATEMENT: This study reported that duloxetine significantly alleviates neuropathic pain induced by paclitaxel and is related to poly ADP-ribose polymerase (PARP), tumor suppressor gene p53, and apoptosis regulator the Bcl2 family. Our findings thus not only provide important guidance to support duloxetine to become the first standard chemotherapy-induced peripheral neuropathy (CIPN) drug but also will find potential new targets and positive control for new CIPN drug development.
Collapse
Affiliation(s)
- Yuting Lu
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China (Y.L., P.Z., Q.Z., C.Y., Y.Q., J.S., X.T., J.Z.); Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland (J.Z.)
| | - Peng Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China (Y.L., P.Z., Q.Z., C.Y., Y.Q., J.S., X.T., J.Z.); Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland (J.Z.)
| | - Qiuyan Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China (Y.L., P.Z., Q.Z., C.Y., Y.Q., J.S., X.T., J.Z.); Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland (J.Z.)
| | - Chao Yang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China (Y.L., P.Z., Q.Z., C.Y., Y.Q., J.S., X.T., J.Z.); Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland (J.Z.)
| | - Yangyan Qian
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China (Y.L., P.Z., Q.Z., C.Y., Y.Q., J.S., X.T., J.Z.); Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland (J.Z.)
| | - Jinshuai Suo
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China (Y.L., P.Z., Q.Z., C.Y., Y.Q., J.S., X.T., J.Z.); Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland (J.Z.)
| | - Xinxia Tao
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China (Y.L., P.Z., Q.Z., C.Y., Y.Q., J.S., X.T., J.Z.); Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland (J.Z.)
| | - Jing Zhu
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China (Y.L., P.Z., Q.Z., C.Y., Y.Q., J.S., X.T., J.Z.); Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland (J.Z.)
| |
Collapse
|
|
37
|
Abstract
PURPOSE OF REVIEW The current review addresses one of the most common neurological disorders, diabetic polyneuropathy (DPN). DPN is debilitating, irreversible and dwarfs the prevalence of most other chronic disorders of the nervous system. Its complications include foot ulceration, amputation, falling and intractable neuropathic pain. Moreover, tight control of hyperglycemia reduces the incidence of DPN in type 1 diabetes mellitus but its role in type 2 diabetes mellitus is less clear. RECENT FINDINGS New therapeutic options to reverse the development of DPN or its associated pain have been proposed but none have significantly changed the clinical approach. The cause of DPN remains controversial traditionally focused on the impact of metabolic abnormalities, polyol flux, microvascular changes, mitochondria, oxidative stress, lipid biology and others. In particular, there has been less attention toward how this chronic disorder alters peripheral neurobiology. It is now clear that in chronic models of diabetes mellitus there exists a unique form of neurodegeneration with a range of protein, mRNA and microRNA alterations to consider. How to reconcile these molecular and structural alterations with metabolic mechanisms is a challenge. In sensory neurons alone, a primary target of DPN, both central perikaryal cytoplasmic and nuclear changes and altered distal sensory axon terminal plasticity may be involved. SUMMARY In this review, the current therapeutic status of DPN is described with greater emphasis on some new but selected thoughts on its neurobiology. New mechanistic understanding will be essential to developing precision therapeutics for DPN.
Collapse
|
|
38
|
Njan AA, Adenuga FO, Ajayi AM, Sotunde O, Ologe MO, Olaoye SO, Erdogan ON, Iwalewa OE. Neuroprotective and memory-enhancing effects of methanolic leaf extract of Peristrophe bicalyculata in rat model of type 2 diabetes mellitus. Heliyon 2020; 6:e04011. [PMID: 32490237 PMCID: PMC7256363 DOI: 10.1016/j.heliyon.2020.e04011] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 02/04/2020] [Accepted: 05/14/2020] [Indexed: 12/03/2022] Open
Abstract
This study investigated the effect of methanolic leaf extract of Peristrophe Bicalyculata (MEPb) on type 2 diabetes mellitus (T2DM) associated cognitive decline in Wistar rats. 36 male rats weighing 130-200 g were assigned into 6 groups (n = 6) as follows: normal control, diabetic control, pioglitazone-treated diabetic and three MEPb-treated diabetic groups, type 2 diabetes mellitus was induced with low dose streptozocin (STZ) injection following 3 weeks of high fat diet (HFD) intake. Thirty days after diabetes induction, rats exhibited marked and persistent hyperglycemia, animals were treated with MEPb (50, 100 and 200 mg/kg) and pioglitazone (10 mg/kg) as standard. Morris water maze (MWM) test and Novel object recognition test (NORT) were used to assess learning and memory. Blood glucose level, oxidative stress makers, pro-inflammatory marker and acetylcholinestarase activities were analysed. Both MEPb and pioglitazone significantly (P < 0.05) reduced escape latency in treated animals compared to the diabetic control group in the MWM test. Methanolic leaf extract of Peristrophe bicalyculata and pioglitazone also significantly (P < 0.05) increased discrimination index in treated animals compared to the diabetic control group in the novel object recognition test. Serum, brain and liver MDA levels were significantly (P < 0.05) decreased in MEPb and pioglitazone treated rats compared to diabetic control. Serum and liver GSH as well as CAT levels were significantly (P < 0.05) increased while brain GSH and CAT levels shows apparent increase in MEPb and pioglitazone treated rats compared with diabetic control. Treatment with MEPb caused a significant (P < 0.05) decrease in brain nitrite level, interleukin 6 and acetylcholinesterase activity compared to diabetic control group. We conclude that Methanolic leaf extract of Peristrophe bicalyculata enhanced antioxidant capacity and prevented neuroinflammation, consequently improving brain neuronal cholinergic function in experimental animals.
Collapse
Affiliation(s)
- Anoka A. Njan
- Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria
| | - Francisca O. Adenuga
- Neuropharmacology and Ethnopharmacology Unit, Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Abayomi M. Ajayi
- Neuropharmacology and Ethnopharmacology Unit, Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Olasubomi Sotunde
- Neuropharmacology and Ethnopharmacology Unit, Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Mary O. Ologe
- Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria
| | | | - Ozlem Nazan Erdogan
- Department of Pharmacy Management, School of Pharmacy, Istanbul University, Beyazit, Istanbul 34116, Turkey
| | - Olugbenga E. Iwalewa
- Neuropharmacology and Ethnopharmacology Unit, Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
| |
Collapse
|
|
39
|
Chang JF, Wu CC, Hsieh CY, Li YY, Wang TM, Liou JC. A Joint Evaluation of Impaired Cardiac Sympathetic Responses and Malnutrition-Inflammation Cachexia for Mortality Risks in Hemodialysis Patients. Front Med (Lausanne) 2020; 7:99. [PMID: 32292788 PMCID: PMC7135880 DOI: 10.3389/fmed.2020.00099] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 03/05/2020] [Indexed: 01/24/2023] Open
Abstract
Background: Cardiac sympathetic response (CSR) and malnutrition-inflammation syndrome (MIS) score are validated assessment tools for patients' health condition. We aim to evaluate the joint effect of CSR and MIS on all-cause and cardiovascular (CV) mortality in patients with hemodialysis (HD). Methods: Changes in normalized low frequency (ΔnLF) during HD were utilized for quantification of CSR. Unadjusted and adjusted hazard ratios (aHRs) of mortality risks were analyzed in different groups of ΔnLF and MIS score. Results: In multivariate analysis, higher ΔnLF was related to all-cause, CV and sudden cardiac deaths [aHR: 0.78 (95% confidence interval (CI): 0.72–0.85), 0.78 (95% CI: 0.70–0.87), and 0.74 (95% CI: 0.63–0.87), respectively]. Higher MIS score was associated with incremental risks of all-cause, CV and sudden cardiac deaths [aHR: 1.36 (95% CI: 1.13–1.63), 1.33 (95% CI: 1.06 – 1.38), and 1.50 (95% CI: 1.07–2.11), respectively]. Patients with combined lower ΔnLF (≤6.8 nu) and higher MIS score were at the greatest risk of all-cause and CV mortality [aHR: 5.64 (95% CI: 1.14–18.09) and 5.86 (95% CI: 1.64–13.65), respectively]. Conclusion: Our data indicate a joint evaluation of CSR and MIS score to identify patients at high risk of death is more comprehensive and convincing. Considering the extremely high prevalence of cardiac autonomic neuropathy and malnutrition-inflammation cachexia in HD population, a non-invasive monitoring system composed of CSR analyzer and MIS score calculator should be developed in the artificial intelligence-based prediction of clinical events.
Collapse
Affiliation(s)
- Jia-Feng Chang
- Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.,Graduate Institute of Aerospace and Undersea Medicine, Academy of Medicine, National Defense Medical Center, Taipei, Taiwan.,Division of Nephrology, Department of Internal Medicine, En Chu Kong Hospital, New Taipei City, Taiwan.,Department of Nursing, Yuanpei University of Medical Technology, Hsinchu, Taiwan.,Renal Care Joint Foundation, New Taipei City, Taiwan.,Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chang-Chin Wu
- Department of Biomedical Engineering, Yuanpei University of Medical Technology, Hsinchu, Taiwan.,Department of Orthopedics, En Chu Kong Hospital, New Taipei City, Taiwan
| | - Chih-Yu Hsieh
- Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yen-Yao Li
- Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Chiayi City, Taiwan.,College of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Ting-Ming Wang
- Department of Orthopaedic Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Jian-Chiun Liou
- School of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan
| |
Collapse
|
|
40
|
Naseri R, Farzaei F, Fakhri S, El-Senduny FF, Altouhamy M, Bahramsoltani R, Ebrahimi F, Rahimi R, Farzaei MH. Polyphenols for diabetes associated neuropathy: Pharmacological targets and clinical perspective. Daru 2019; 27:781-798. [PMID: 31352568 PMCID: PMC6895369 DOI: 10.1007/s40199-019-00289-w] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Accepted: 07/01/2019] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVES Diabetic neuropathy (DNP) is a widespread and debilitating complication with complex pathophysiology that is caused by neuronal dysfunction in diabetic patients. Conventional therapeutics for DNP are quite challenging due to their serious adverse effects. Hence, there is a need to investigate novel effective and safe options. The novelty of the present study was to provide available therapeutic approaches, emerging molecular mechanisms, signaling pathways and future directions of DNP as well as polyphenols' effect, which accordingly, give new insights for paving the way for novel treatments in DNP. EVIDENCE ACQUISITION A comprehensive review was done in electronic databases including Medline, PubMed, Web of Science, Scopus, national database (Irandoc and SID), and related articles regarding metabolic pathways on the pathogenesis of DNP as well as the polyphenols' effect. The keywords "diabetic neuropathy" and "diabetes mellitus" in the title/abstract and "polyphenol" in the whole text were used. Data were collected from inception until May 2019. RESULTS DNP complications is mostly related to a poor glycemic control and metabolic imbalances mainly inflammation and oxidative stress. Several signaling and molecular pathways play key roles in the pathogenesis and progression of DNP. Among natural entities, polyphenols are suggested as multi-target alternatives affecting most of these pathogenesis mechanisms in DNP. CONCLUSION The findings revealed novel pathogenicity signaling pathways of DNP and affirmed the auspicious role of polyphenols to tackle these destructive pathways in order to prevent, manage, and treat various diseases. Graphical Abstract .
Collapse
Affiliation(s)
- Rozita Naseri
- Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Fatemeh Farzaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Sajad Fakhri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Fardous F El-Senduny
- Biochemistry division, Chemistry Department, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt
| | - Miram Altouhamy
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Roodabeh Bahramsoltani
- Department of Pharmacy in Persian Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran
- PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Farnaz Ebrahimi
- Pharmacy students` research committee, School of pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Roja Rahimi
- Department of Pharmacy in Persian Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran
- PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| |
Collapse
|
|
41
|
Pieralice S, Vari R, Minutolo A, Maurizi AR, Fioriti E, Napoli N, Pozzilli P, Manfrini S, Maddaloni E. Biomarkers of response to alpha-lipoic acid ± palmitoiletanolamide treatment in patients with diabetes and symptoms of peripheral neuropathy. Endocrine 2019; 66:178-184. [PMID: 30949911 DOI: 10.1007/s12020-019-01917-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Accepted: 03/27/2019] [Indexed: 12/19/2022]
Abstract
PURPOSE To evaluate the effect of oral alpha-lipoic acid (ALA) ± palmitoyl-ethanolamide (PEA) on neuropathic symptoms in patients with diabetic peripheral neuropathy (DPN) and to identify factors related to the efficacy of the treatment. METHODS This is a retrospective observational pilot study evaluating 49 patients with diabetes and positive Neuropathy Symptoms Score (NSS). Clinical and biochemical variables, including NSS, were compared between untreated patients and patients treated with oral 600 mg/day ALA ± 600 mg/day PEA at baseline (first occurrence of NSS ≥ 3) and at least 2 months after baseline. Number of days between treatment initiation and symptoms' relief and related factors were also investigated. RESULTS Thirty subjects were treated with ALA ± PEA and 19 subjects did not receive any specific treatment for neuropathy symptoms. Follow-up visits occurred after 98 ± 46 days. NSS significantly decreased in patients treated with ALA ± PEA (5.4 ± 1.3 at baseline vs. 1.7 ± 2.4 at follow-up, p < 0.001), but not in untreated patients (p = 0.164). Subjects treated with ALA ± PEA reported a mean time from treatment initiation to symptoms' relief of 18.4 ± 9.0 days. The number of days of treatment needed for symptoms' relief was inversely related to HDL-cholesterol levels (r = -0.503, p = 0.010) and to eGFR (r = -0.428, p = 0.033), whereas there was no significant relationship between time to symptoms' relief and age, HbA1c, lipid profile and the severity of symptoms at baseline. CONCLUSIONS This study documents that oral administration of ALA ± PEA helps in controlling neuropathy symptoms in diabetes. Moreover, our data show that higher HDL-c levels and better renal function are associated to a faster therapeutic effect, suggesting them as biomarkers of response to therapy with ALA ± PEA.
Collapse
Affiliation(s)
- Silvia Pieralice
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy
| | - Riccardo Vari
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy
| | - Alessandra Minutolo
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy
| | - Anna Rita Maurizi
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy
| | - Elvira Fioriti
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy
| | - Nicola Napoli
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy
| | - Paolo Pozzilli
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy
| | - Silvia Manfrini
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy
| | - Ernesto Maddaloni
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy.
| |
Collapse
|
|
42
|
Berberine ameliorates diabetic neuropathic pain in a rat model: involvement of oxidative stress, inflammation, and μ-opioid receptors. Naunyn Schmiedebergs Arch Pharmacol 2019; 392:1141-1149. [DOI: 10.1007/s00210-019-01659-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 04/26/2019] [Indexed: 01/12/2023]
|
|
43
|
Gallego FQ, Miranda CA, Sinzato YK, Iessi IL, Dallaqua B, Pando RH, Rocha NS, Volpato GT, Damasceno DC. Temporal analysis of distribution pattern of islet cells and antioxidant enzymes for diabetes onset in postnatal critical development window in rats. Life Sci 2019; 226:57-67. [PMID: 30930115 DOI: 10.1016/j.lfs.2019.03.061] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 03/12/2019] [Accepted: 03/25/2019] [Indexed: 12/22/2022]
Abstract
AIM At performing a temporal analysis of the distribution pattern of islet endocrine cells and antioxidant enzymes in diabetic rats during the post-natal critical development window. MAIN METHODS The newborns received streptozotocin (STZ) at birth for diabetes induction, and control females received the vehicle. The animals were euthanized at different lifetimes: D5, D10, D15, and D30. Morphological analysis of pancreas and biochemical assays was performed. KEY FINDINGS The STZ-induced rats presented irregular shape of islet on D5 and there was an attempt to restore of this shape in other life moment studied. There was an increase progressive in islet area, however they maintained smaller than those of control rats, with lower labeling intensity for insulin, higher for glucagon and somatostatin, lower for SOD-1 was lower in the islets of the STZ-induced animals at all times studied and for GSH-Px in D10 and D30. SIGNIFICANCE Although STZ-induced diabetic rats presented compensatory mechanisms to restore the mass of endocrine cells, this was not sufficient since these rats developed the diabetic state. This was confirmed by the oral glucose tolerance test from D30. In addition, the delta (δ)-cells presented ectopic location in islets, indicating a possible relationship for beta (β)-cell mass restoration. There was a response of the pancreas to reduce the hyperglycemia in the first month of life. Furthermore, the cells from the endocrine pancreas of diabetic animals show a decline of antioxidant enzymatic, contributing to the increased susceptibility of cells to hyperglycemia-induced ROS in this postnatal critical development window.
Collapse
Affiliation(s)
- Franciane Quintanilha Gallego
- Laboratory of Experimental Research of Gynecology and Obstetrics, Postgraduate Course of Gynecology, Obstetrics and Mastology, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Carolina Abreu Miranda
- Laboratory of Experimental Research of Gynecology and Obstetrics, Postgraduate Course of Gynecology, Obstetrics and Mastology, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Yuri Karen Sinzato
- Laboratory of Experimental Research of Gynecology and Obstetrics, Postgraduate Course of Gynecology, Obstetrics and Mastology, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Isabela Lovizutto Iessi
- Laboratory of Experimental Research of Gynecology and Obstetrics, Postgraduate Course of Gynecology, Obstetrics and Mastology, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Bruna Dallaqua
- DeVry Ruy Barbosa School (DeVry Brazil Group), Salvador, Bahia State, Brazil
| | - Rogelio Hernandez Pando
- Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán", Mexico City, Mexico
| | - Noeme Sousa Rocha
- Department of Pathology, School of Veterinary Medicine and Animal Science (FMVZ), São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Gustavo Tadeu Volpato
- Laboratory of System Physiology and Reproductive Toxicology, Institute of Biological and Health Sciences, Federal University of Mato Grosso (UFMT), Barra do Garças, Mato Grosso State, Brazil
| | - Débora Cristina Damasceno
- Laboratory of Experimental Research of Gynecology and Obstetrics, Postgraduate Course of Gynecology, Obstetrics and Mastology, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
| |
Collapse
|
|
44
|
Patel SN, Lau-Cam CA. The Effect of Taurine and Its Immediate Homologs on Diabetes-Induced Oxidative Stress in the Brain and Spinal Cord of Rats. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 975 Pt 1:337-351. [PMID: 28849468 DOI: 10.1007/978-94-024-1079-2_30] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
This study has examined the acute effects of taurine (TAU) and of its two immediate homologs aminomethanesulfonic acid (AMSA) and homotaurine (HTAU) on the oxidative stress that develops in the brain of rats as a result of type 2 diabetes mellitus. Male Sprague-Dawley rats, 220-225 g in weight, were divided into groups of 6 each, and treated with a single intraperitoneal (i.p.) dose of streptozotocin (STZ) in 10 mM citrate buffer pH 4.5 (60 mg/kg). The treatment compound (AMSA, HTAU or TAU) was administered by the i.p. route in two equal doses (1.2 mM/kg each) at 75 and 45 min before STZ. Control rats received only 10 mM citrate buffer pH 4.5 or only STZ by the i.p. route. The rats were sacrificed at 24 h after a dosing with STZ under general anesthesia, and their brains and spinal cords collected by the freeze clamp technique. A portion of brain, of a brain area (cerebellum, cortex, brain stem) or of spinal cord from each animal was extracted into 0.1 M PBS pH 7.4, and the extract was used for the assay of malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). An extract for the assay of the reduced (GSH) and disulfide (GGSG) forms of glutathione was prepared in similar manner but using 2% metaphosphoric acid plus 0.1 M PBS pH 8.0 as the extracting medium. Diabetes was found to markedly increase the formation of MDA (by 160-202%), NO (by 138-313%) and GSSG (by 103-241%), and to lower the values of GSH (by 57-65%), GSH/GSSG ratio (79-89%) and activities of CAT (by 61-69%), GPx (by 52-66%) and SOD (by 55-68%) in the brain, brain areas and spinal cord relative to corresponding control values (all at p < 0.001). These effects were reduced to values that were generally at least one-half of those seen in untreated diabetic rats, with TAU providing a greater attenuation of the formation of MDA and NO, an about similar action on the depletion of GSH, and a lower action on the decrease in the GSH/GSSG ratio caused by diabetes than either AMSA or HMTAU. In contrast AMSA and HMTAU were about equipotent with each other and more potent than TAU in preventing the loss of antioxidant enzyme activities associated with diabetes. In short, pretreating diabetic rats with AMSA, HMTAU or TAU is found to protect the brain against changes in biochemical parameters indicative of oxidative stress, with potency differences among the test compounds varying within a narrow range.
Collapse
Affiliation(s)
- Sanket N Patel
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, 11439, USA
| | - Cesar A Lau-Cam
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, 11439, USA.
| |
Collapse
|
|
45
|
Metwalley KA, Hamed SA, Farghaly HS. Cardiac autonomic function in children with type 1 diabetes. Eur J Pediatr 2018; 177:805-813. [PMID: 29500542 DOI: 10.1007/s00431-018-3122-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2017] [Revised: 02/15/2018] [Accepted: 02/19/2018] [Indexed: 01/09/2023]
Abstract
UNLABELLED Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). This study aimed to evaluate cardiac autonomic nervous system (ANS) function in children with T1D and its relation to different demographic, clinical and laboratory variable. This cross-sectional study included 60 children with T1D (mean age = 15.1 ± 3.3 years; duration of diabetes = 7.95 ± 3.83 years). The following 8 non-invasive autonomic testing were used for evaluation: heart rate at rest and in response to active standing (30:15 ratio), deep breathing and Valsalva maneuver (indicating parasympathetic function); blood pressure response to standing (orthostatic hypotension or OH), sustained handgrip and cold; and heart rate response to standing or positional orthostatic tachycardia syndrome or POTs (indicating sympathetic function). None had clinically manifest CAN. Compared to healthy children (5%), 36.67% of children with T1D had ≥ 2 abnormal tests (i.e., CAN) (P = 0.0001) which included significantly abnormal heart rate response to standing (POTs) (P = 0.052), active standing (30:15 ratio) (P = 0.0001) and Valsalva maneuver (P = 0.0001), indicating parasympathetic autonomic dysfunction, and blood pressure response to cold (P = 0.01), indicating sympathetic autonomic dysfunction. 54.55, 27.27 and 18.18% had early, definite and severe dysfunction of ANS. All patients had sensorimotor peripheral neuropathy. The longer duration of diabetes (> 5 years), presence of diabetic complications and worse glycemic control were significantly associated with CAN. CONCLUSIONS The study concluded that both parasympathetic and sympathetic autonomic dysfunctions are common in children with T1D particularly with longer duration of diabetes and presence of microvascular complications. What is Known: • Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). • Limited studies evaluated CAN in children with T1D. What is New: • CAN is common in children with T1D. • Cardiac autonomic functions should be assessed in children with T1D particularly in presence of microvascular complications.
Collapse
Affiliation(s)
| | - Sherifa Ahmed Hamed
- Department of Neurology and Psychiatry, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Hekma Saad Farghaly
- Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt.
| |
Collapse
|
|
46
|
R(+)-Thioctic Acid Effects on Oxidative Stress and Peripheral Neuropathy in Type II Diabetic Patients: Preliminary Results by Electron Paramagnetic Resonance and Electroneurography. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:1767265. [PMID: 29849866 PMCID: PMC5914101 DOI: 10.1155/2018/1767265] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Revised: 11/02/2017] [Accepted: 12/27/2017] [Indexed: 12/15/2022]
Abstract
Objectives Diabetic neuropathy is the most common complication of diabetes. The idea of alterations in energy metabolism in diabetes is emerging. The biogenic antioxidant R(+)-thioctic acid has been successfully used in the treatment of diabetic polyneuropathic (DPN) patients. Methods The effects of R(+)-thioctic acid (1 tablet, 1.6 g) administration were evaluated in 12 DPN patients at baseline and at 15, 30, 60, and 120 administration days throughout the assessment of oxidative stress (OxS); ROS production rate by electron paramagnetic resonance (EPR) technique; and oxidative damage biomarkers (thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PC)), electroneurography (ENG) and visual analogue scale. Results Supplementation induced significant changes (p < 0.05) at 30 and 60 days. ROS production rate up to -16%; TBARS (-31%), PC (-38%), and TAC up to +48%. Motor nerve conduction velocity in SPE and ulnar nerves (+22% and +16%) and sensor conduction velocity in sural and median nerves (+22% and +5%). Patients reported a general wellness sensation improvement (+35%) at 30 days: lower limb pain sensation (-40%) and upper limbs (-23%). Conclusion The results strongly indicate that an increased antioxidant capacity plays an important role in OxS, nerve conduction velocity, pain, and general wellness improvement. Nevertheless, the effects of the antioxidant compound were found positive up to 60 days. Then, a hormesis effect was observed. Novelty of the research would be a challenge for investigators to carefully address issues, including dose range factors, appropriate administration time, and targeting population to counteract possible "boomerang effects." The great number of monitored parameters would firmly stress these conclusions.
Collapse
|
|
47
|
Jain M, Devan S, Jaisankar D, Swaminathan G, Pardhan S, Raman R. Pupillary Abnormalities with Varying Severity of Diabetic Retinopathy. Sci Rep 2018; 8:5636. [PMID: 29618794 PMCID: PMC5884827 DOI: 10.1038/s41598-018-24015-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 03/21/2018] [Indexed: 11/23/2022] Open
Abstract
Our aim is to study the dynamics of pupillary abnormalities in varying severity of diabetic retinopathy. A non-interventional case-control study with 405 eyes of 244 subjects with diabetes, and 41 eyes of 26 subjects with no history of diabetes was done. Diabetes group was classified according to retinopathy severity: no retinopathy, mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR and proliferative diabetic retinopathy (PDR). After dark adaptation, pupil size and flashlight response were captured with an infrared camera. Baseline Pupil Diameter (BPD), Amplitude of Pupillary Constriction (APC), Velocity of Pupillary Constriction (VPC) and Velocity of Pupillary Dilatation (VPD). Compared to controls, mean BPD decreased with increasing severity of diabetic retinopathy. Mean APC in control group was 1.73 ± 0.37 mm and reduced in mild NPDR (1.57 ± 0.39, p = 1.000), moderate NPDR (1.51 ± 0.44, p = 0.152) and found to be significant reduced in severe NPDR (1.43 ± 0.48, p = 0.001) and PDR (1.29 ± 0.43, p = 0.008). Compared to controls, mean VPC decreased progressively with increasing severity of retinopathy, with a maximal difference in the PDR group. Mean VPD as compared to the control group was significantly reduced in the no DR (p = 0.03), mild NPDR (p = 0.038), moderate NPDR (p = 0.05), PDR group (p = 0.02). We found pupillary dynamics are abnormal in early stages of diabetic retinopathy and progress with increasing retinopathy severity.
Collapse
Affiliation(s)
- Mukesh Jain
- Shri Bhagwan Mahavir Vitreoretinal services, 18, College Road, Sankara Nethralaya, Chennai, 600 006, Tamil Nadu, India
| | - Sandeep Devan
- Elite School of Optometry, 8 GST Road, Chennai, 600016, Tamil Nadu, India
| | - Durgasri Jaisankar
- Shri Bhagwan Mahavir Vitreoretinal services, 18, College Road, Sankara Nethralaya, Chennai, 600 006, Tamil Nadu, India.,Vision and Eye Research Unit (VERU), Postgraduate Medical Institute, Anglia Ruskin University, Cambridge, CB1 1PT, UK
| | - Gayathri Swaminathan
- Shri Bhagwan Mahavir Vitreoretinal services, 18, College Road, Sankara Nethralaya, Chennai, 600 006, Tamil Nadu, India
| | - Shahina Pardhan
- Vision and Eye Research Unit (VERU), Postgraduate Medical Institute, Anglia Ruskin University, Cambridge, CB1 1PT, UK
| | - Rajiv Raman
- Shri Bhagwan Mahavir Vitreoretinal services, 18, College Road, Sankara Nethralaya, Chennai, 600 006, Tamil Nadu, India. .,Vision and Eye Research Unit (VERU), Postgraduate Medical Institute, Anglia Ruskin University, Cambridge, CB1 1PT, UK.
| |
Collapse
|
|
48
|
Ma J, Kavelaars A, Dougherty PM, Heijnen CJ. Beyond symptomatic relief for chemotherapy-induced peripheral neuropathy: Targeting the source. Cancer 2018; 124:2289-2298. [PMID: 29461625 DOI: 10.1002/cncr.31248] [Citation(s) in RCA: 110] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Revised: 12/21/2017] [Accepted: 12/29/2017] [Indexed: 12/23/2022]
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse side effect of many chemotherapeutic agents, affecting >60% of patients with cancer. Moreover, CIPN persists long into survivorship in approximately 20% to 30% of these patients. To the authors' knowledge, no drugs have been approved to date by the US Food and Drug Administration to effectively manage chemotherapy-induced neuropathic pain. The majority of the drugs tested for the management of CIPN aim at symptom relief, including pain and paresthesia, yet are not very efficacious. The authors propose that there is a need to acquire a more thorough understanding of the etiology of CIPN so that effective, mechanism-based, disease-modifying interventions can be developed. It is important to note that such interventions should not interfere with the antitumor effects of chemotherapy. Mitochondria are rod-shaped cellular organelles that represent the powerhouses of the cell, in that they convert oxygen and nutrients into the cellular energy "currency" adenosine triphosphate. In addition, mitochondria regulate cell death. Neuronal mitochondrial dysfunction and the associated nitro-oxidative stress represent crucial final common pathways of CIPN. Herein, the authors discuss the potential to prevent or reverse CIPN by protecting mitochondria and/or inhibiting nitro-oxidative stress with novel potential drugs, including the mitochondrial protectant pifithrin-μ, histone deacetylase 6 inhibitors, metformin, antioxidants, peroxynitrite decomposition catalysts, and anti-inflammatory mediators including interleukin 10. This review hopefully will contribute toward bridging the gap between preclinical research and the development of realistic novel therapeutic strategies to prevent or reverse the devastating neurotoxic effects of chemotherapy on the (peripheral) nervous system. Cancer 2018;124:2289-98. © 2018 American Cancer Society.
Collapse
Affiliation(s)
- Jiacheng Ma
- Neuroimmunology Laboratory, Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Annemieke Kavelaars
- Neuroimmunology Laboratory, Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Patrick M Dougherty
- Department of Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Cobi J Heijnen
- Neuroimmunology Laboratory, Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, Texas
| |
Collapse
|
|
49
|
Yurt KK, Kaplan S. As a painkiller: a review of pre- and postnatal non-steroidal anti-inflammatory drug exposure effects on the nervous systems. Inflammopharmacology 2017; 26:15-28. [DOI: 10.1007/s10787-017-0434-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Accepted: 12/10/2017] [Indexed: 11/29/2022]
|
|
50
|
Sifuentes-Franco S, Pacheco-Moisés FP, Rodríguez-Carrizalez AD, Miranda-Díaz AG. The Role of Oxidative Stress, Mitochondrial Function, and Autophagy in Diabetic Polyneuropathy. J Diabetes Res 2017; 2017:1673081. [PMID: 29204450 PMCID: PMC5674726 DOI: 10.1155/2017/1673081] [Citation(s) in RCA: 107] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 08/25/2017] [Accepted: 09/12/2017] [Indexed: 02/07/2023] Open
Abstract
Diabetic polyneuropathy (DPN) is the most frequent and prevalent chronic complication of diabetes mellitus (DM). The state of persistent hyperglycemia leads to an increase in the production of cytosolic and mitochondrial reactive oxygen species (ROS) and favors deregulation of the antioxidant defenses that are capable of activating diverse metabolic pathways which trigger the presence of nitro-oxidative stress (NOS) and endoplasmic reticulum stress. Hyperglycemia provokes the appearance of micro- and macrovascular complications and favors oxidative damage to the macromolecules (lipids, carbohydrates, and proteins) with an increase in products that damage the DNA. Hyperglycemia produces mitochondrial dysfunction with deregulation between mitochondrial fission/fusion and regulatory factors. Mitochondrial fission appears early in diabetic neuropathy with the ability to facilitate mitochondrial fragmentation. Autophagy is a catabolic process induced by oxidative stress that involves the formation of vesicles by the lysosomes. Autophagy protects cells from diverse stress factors and routine deterioration. Clarification of the mechanisms involved in the appearance of complications in DM will facilitate the selection of specific therapeutic options based on the mechanisms involved in the metabolic pathways affected. Nowadays, the antioxidant agents consumed exogenously form an adjuvant therapeutic alternative in chronic degenerative metabolic diseases, such as DM.
Collapse
Affiliation(s)
- Sonia Sifuentes-Franco
- Institute of Experimental and Clinical Therapeutics, Department of Physiology, University Health Sciences Centre, University of Guadalajara, Guadalajara, JAL, Mexico
| | - Fermín Paul Pacheco-Moisés
- Department of Chemistry, University Centre for Exact and Engineering Sciences, University of Guadalajara, Guadalajara, JAL, Mexico
| | - Adolfo Daniel Rodríguez-Carrizalez
- Institute of Experimental and Clinical Therapeutics, Department of Physiology, University Health Sciences Centre, University of Guadalajara, Guadalajara, JAL, Mexico
| | - Alejandra Guillermina Miranda-Díaz
- Institute of Experimental and Clinical Therapeutics, Department of Physiology, University Health Sciences Centre, University of Guadalajara, Guadalajara, JAL, Mexico
| |
Collapse
|