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Sadikan MZ, Lambuk L, Reshidan N, Ahmad Hairi H, Abd Ghapor AA, Mohamud R, Abdul Nasir NA. Molecular Mechanisms of Vitamin E in Ocular Neurodegenerative Disorders: An Update on the Emerging Evidence and Therapeutic Implications. J Ocul Pharmacol Ther 2025; 41:89-100. [PMID: 39778903 DOI: 10.1089/jop.2024.0125] [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] [Indexed: 01/11/2025] Open
Abstract
Vitamin E is renowned for its potent antioxidant properties, crucial for shielding cells against oxidative stress and damage. Deficiency in this vitamin can lead to various health issues, including neurodegenerative diseases, due to its pivotal role in preserving cell membrane integrity and combating cellular oxidative damage. While its importance for overall health, including neurodegeneration, is acknowledged, the specific correlation between vitamin E deficiency and distinct ocular neurodegenerative disorders need to be further explored. This review delves into the molecular mechanisms of vitamin E in ocular neurodegenerative disorders; diabetic retinopathy, age-related macular degeneration, glaucoma, and cataracts, and emphasising the therapeutic implications drawn from existing evidence. Relationship between vitamin E and ocular neurodegenerative disorders is widely researched on, with its primary protective mechanisms attributed to its antioxidant and anti-inflammatory properties. However, studies on the supplementation of vitamin E among human subjects present mixed results, suggesting its complexities and variability depending on factors such as the specific disorder, disease stage, genetic differences, and form of vitamin E utilized. In conclusion, while vitamin E holds promise in mitigating ocular neurodegeneration through its antioxidant and anti-inflammatory properties, its supplementation's efficacy remains nuanced and context dependent. More research works are essential to elucidate its precise role and therapeutic potential in combating various ocular neurodegenerative disorders.
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Affiliation(s)
- Muhammad Zulfiqah Sadikan
- Department of Pharmacology, Faculty of Medicine, Manipal University College Malaysia, Melaka, Malaysia
| | - Lidawani Lambuk
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
| | - Nurhidayah Reshidan
- School of Biology, Faculty of Applied Sciences, Universiti Teknologi MARA, Selangor, Malaysia
| | - Haryati Ahmad Hairi
- Department of Biochemistry, Faculty of Medicine, Manipal University College Malaysia, Melaka, Malaysia
| | - Afiqq Aiman Abd Ghapor
- Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia
| | - Rohimah Mohamud
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
| | - Nurul Alimah Abdul Nasir
- Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia
- Department of Medical Education, Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia
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D'Angelo A, Lixi F, Vitiello L, Gagliardi V, Pellegrino A, Giannaccare G. The Role of Diet and Oral Supplementation for the Management of Diabetic Retinopathy and Diabetic Macular Edema: A Narrative Review. BIOMED RESEARCH INTERNATIONAL 2025; 2025:6654976. [PMID: 40041571 PMCID: PMC11876532 DOI: 10.1155/bmri/6654976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 02/08/2025] [Indexed: 03/06/2025]
Abstract
Globally, diabetic retinopathy (DR) and diabetic macular edema (DME) are the leading causes of visual loss in working people. Current treatment approaches mostly target proliferative DR and DME, such as intravitreal injections of antivascular endothelial growth factor agents and laser photocoagulation. Before DR progresses into the more severe, sight-threatening proliferative stage, patients with early stages of the disease must get early and appropriate care. It has been suggested that nutraceuticals, which are natural functional foods with minimal adverse effects, may help diabetic patients with DR and DME. Several in vitro and in vivo studies were carried out over the last years, showing the potential benefits of several nutraceuticals in DR due to their neuroprotective, vasoprotective, anti-inflammatory, and antioxidant properties. Although most of the research is restricted to animal models and many nutraceuticals have low bioavailability, these compounds may adjuvate and implement conventional DR therapies. The purpose of this review is (i) to summarize the complex pathophysiology underlying DR and DME and (ii) to examine the main natural-derived molecules and dietary habits that can assist conventional therapies for the clinical management of DR and DME.
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Affiliation(s)
- Angela D'Angelo
- Department of Clinical Sciences and Community Health–Department of Excellence 2023–2027, University of Milan, Milan, Italy
| | - Filippo Lixi
- Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy
| | - Livio Vitiello
- Department of Head and Neck, Eye Unit, “Luigi Curto” Hospital-Azienda Sanitaria Locale Salerno, Polla, Italy
| | - Vincenzo Gagliardi
- Department of Head and Neck, Eye Unit, “Luigi Curto” Hospital-Azienda Sanitaria Locale Salerno, Polla, Italy
| | - Alfonso Pellegrino
- Department of Head and Neck, Eye Unit, “Luigi Curto” Hospital-Azienda Sanitaria Locale Salerno, Polla, Italy
| | - Giuseppe Giannaccare
- Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy
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Alahmari H, Liu CC, Rubin E, Lin VY, Rodriguez P, Chang KC. Vitamin C alleviates hyperglycemic stress in retinal pigment epithelial cells. Mol Biol Rep 2024; 51:637. [PMID: 38727927 DOI: 10.1007/s11033-024-09595-2] [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] [Received: 02/02/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024]
Abstract
BACKGROUND Retinal pigment epithelial cells (RPECs) are a type of retinal cells that structurally and physiologically support photoreceptors. However, hyperglycemia has been shown to play a critical role in the progression of diabetic retinopathy (DR), which is one of the leading causes of vision impairment. In the diabetic eye, the high glucose environment damages RPECs via the induction of oxidative stress, leading to the release of excess reactive oxygen species (ROS) and triggering apoptosis. In this study, we aim to investigate the antioxidant mechanism of Vitamin C in reducing hyperglycemia-induced stress and whether this mechanism can preserve the function of RPECs. METHODS AND RESULTS ARPE-19 cells were treated with high glucose in the presence or absence of Vitamin C. Cell viability was measured by MTT assay. Cleaved poly ADP-ribose polymerase (PARP) was used to identify apoptosis in the cells. ROS were detected by the DCFH-DA reaction. The accumulation of sorbitol in the aldose reductase (AR) polyol pathway was determined using the sorbitol detection assay. Primary mouse RPECs were isolated from adult mice and identified by Rpe65 expression. The mitochondrial damage was measured by mitochondrial membrane depolarization. Our results showed that high glucose conditions reduce cell viability in RPECs while Vitamin C can restore cell viability, compared to the vehicle treatment. We also demonstrated that Vitamin C reduces hyperglycemia-induced ROS production and prevents cell apoptosis in RPECs in an AR-independent pathway. CONCLUSIONS These results suggest that Vitamin C is not only a nutritional necessity but also an adjuvant that can be combined with AR inhibitors for alleviating hyperglycemic stress in RPECs.
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Affiliation(s)
- Hamid Alahmari
- Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA
| | - Chia-Chun Liu
- Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA
| | - Elizabeth Rubin
- Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA
| | - Venice Y Lin
- Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA
- North Allegheny Senior High School, Wexford, PA, 15090, USA
| | - Paul Rodriguez
- Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA
| | - Kun-Che Chang
- Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA.
- Department of Neurobiology, Center of Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
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Armenia A, Badriyya E, Rahmita S, Rachmaini F, Abdillah R. Malondialdehyde and TNF-α lowering effects of purified gambier (Uncaria gambir Roxb.) in diabetic rats. J Ayurveda Integr Med 2024; 15:100855. [PMID: 38266537 PMCID: PMC10835436 DOI: 10.1016/j.jaim.2023.100855] [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: 01/06/2023] [Revised: 11/17/2023] [Accepted: 11/20/2023] [Indexed: 01/26/2024] Open
Abstract
BACKGROUND Malondialdehyde (MDA) is one of a dominat marker in oxidative stress condition, and when inflammation occurred tumor necrosis factor- α (TNF-α) played a significant influence in the propagation this process. Purified gambier (Uncaria gambier Roxb.) contained 90% catechin which is proven to have antioxidant activity and may prevent unwanted inflammatory responses during diabetic state. OBJECTIVE The objective of this research was to assess how purified gambier affected plasma MDA and TNF- α levels in alloxan-induced diabetic rats. MATERIAL AND METHODS In this study, 35 rats were used. Alloxan 120 mg/kg BW intraperitoneal injection was administered to induce diabetes conditions in rats. All animals were divided into 5 groups, diabetic control group treated with vehicle, positive control group treated with glibenclamide dose 0.45 mg/kg BW), and treatment groups treated with purified gambier dose of 2.5; 5 and 10 mg/kg BW. All animals were treated respectively for 14 days. Plasma MDA and TNF- α levels were measured on day 3, and 14. RESULTS Two-way ANOVA was applied to analyze all of the data, these findings suggested that purified gambier has antioxidant-related anti-inflammation actions. possesses blood sugar-lowering activity (p<0.05). The plasma MDA and TNF- α level of treatment group were significantly reduced (p<0.05) compared to diabetes control group. CONCLUSION These results depicted that at doses of 2.5-10 mg/kg BW, purified gambier has antioxidant-associated anti-inflammation effects when given for 14 days on diabetic rat model by reducing plasma levels MDA and TNF-α.
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Affiliation(s)
- Armenia Armenia
- Departement of Pharmacology & Clinical Pharmacy, Faculty of Pharmacy, Universitas Andalas, Padang, West Sumatera, Indonesia
| | - Elsa Badriyya
- Departement of Pharmacology & Clinical Pharmacy, Faculty of Pharmacy, Universitas Andalas, Padang, West Sumatera, Indonesia
| | - Sri Rahmita
- Undergraduate Study Program, Faculty of Pharmacy, Universitas Andalas, Padang, West Sumatera, Indonesia
| | - Fitri Rachmaini
- Departement of Pharmacology & Clinical Pharmacy, Faculty of Pharmacy, Universitas Andalas, Padang, West Sumatera, Indonesia
| | - Rahmad Abdillah
- Departement of Pharmacology & Clinical Pharmacy, Faculty of Pharmacy, Universitas Andalas, Padang, West Sumatera, Indonesia.
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Jiang F, Zhou L, Zhang C, Jiang H, Xu Z. Malondialdehyde levels in diabetic retinopathy patients: a systematic review and meta-analysis. Chin Med J (Engl) 2023; 136:1311-1321. [PMID: 37101358 PMCID: PMC10309507 DOI: 10.1097/cm9.0000000000002620] [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: 08/17/2022] [Indexed: 04/28/2023] Open
Abstract
BACKGROUND It remains unclear whether circulating malondialdehyde (MDA) levels change in people with diabetic retinopathy (DR). This systematic review compared circulating MDA levels in diabetic people with and without DR. METHODS PubMed, Medline (Ovid), Embase (Ovid), and Web of Science were searched for case-control studies conducted before May 2022 in English that compared circulating MDA levels in people with and without DR. The following MeSH search terms were used: ("malondialdehyde" or "thiobarbituric acid reactive substances [TBARS]" or "lipid peroxidation" or "oxidative stress") and "diabetic retinopathy." Newcastle-Ottawa Quality Assessment Scale was used to evaluate the quality of the included studies. Random-effects pairwise meta-analysis pooled the effect size with standardized mean difference (SMD) and 95% confidence intervals (CIs). RESULTS This meta-analysis included 29 case-control studies with 1680 people with DR and 1799 people with diabetes but not DR. Compared to people without DR, the circulating MDA levels were higher in those with DR (SMD, 0.897; 95% CI, 0.631 to 1.162; P < 0.001). The study did not identify credible subgroup effects or publication bias and the sensitivity analysis confirmed the robustness of the study. CONCLUSIONS Circulating MDA levels are higher in people with DR compared to those without. Future comparative studies that use more specific methods are required to draw firm conclusions. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022352640.
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Affiliation(s)
- Fanwen Jiang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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Xiong R, Yuan Y, Zhu Z, Wu Y, Ha J, Han X, Wang W, He M. Micronutrients and Diabetic Retinopathy: Evidence From The National Health and Nutrition Examination Survey and a Meta-analysis. Am J Ophthalmol 2022; 238:141-156. [PMID: 35033539 DOI: 10.1016/j.ajo.2022.01.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 12/27/2021] [Accepted: 01/01/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE To investigate the associations between circulating micronutrients (vitamins A, C, D, E, and carotenoids) and risk of diabetic retinopathy (DR). DESIGN Cross-sectional study and meta-analysis. METHODS The cross-sectional study included 517 diabetic participants aged ≥40 years in the 2005-2006 National Health and Nutrition Examination Survey. Serum vitamin D was converted to liquid chromatography-tandem mass spectrometry-equivalent results, while other micronutrients were measured using high-performance liquid chromatography. Presence of DR was determined based on non-mydriatic fundus photographs. A meta-analysis was subsequently performed, which included relevant studies published from January 01, 1990 to December 31, 2020. RESULTS Of the 517 included participants, DR was identified in 159 participants (25.17%). After adjusting for multiple confounders, only serum vitamin C was associated with a lower risk of DR (odds ratio [OR]: 0.60; 95% confidence interval [CI]: 0.38-0.95). A total of 35 studies were included in the subsequent meta-analysis. Comparing 1056 participants with DR to 920 controls, the pooled weighted mean difference (WMD) of vitamin C was -11.01 (95% CI: -19.35 to -2.67). Regarding vitamins D and E, the pooled WMD was -3.06 (95% CI: -5.15 to -0.96) and -3.03 (95% CI: -4.24 to -1.82), respectively. No associations were identified between DR and circulating vitamin A or carotenoids. CONCLUSIONS Lower levels of circulating vitamins C, D, and E were found in DR patients than those without. More high-quality studies are required to assess the real effects of micronutrients on DR.
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Zhang XX, Ji YL, Zhu LP, Wang ZH, Fang CQ, Jiang CH, Pan K, Zhang J, Yin ZQ. Arjunolic acid from Cyclocarya paliurus ameliorates diabetic retinopathy through AMPK/mTOR/HO-1 regulated autophagy pathway. JOURNAL OF ETHNOPHARMACOLOGY 2022; 284:114772. [PMID: 34688801 DOI: 10.1016/j.jep.2021.114772] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 10/05/2021] [Accepted: 10/19/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cyclocarya paliurus (CP) is a traditional Chinese herb and possesses a variety of biological activities including anti-hyperglycemia, anti-hyperlipidemia, antioxidant and anti-inflammation. Arjunolic acid (AA) is an abundant and bioactive ingredient in CP that shows significant protection against many metabolic diseases such as diabetic complication. Diabetic retinopathy (DR) is a serious complication of diabetes and may lead to vision loss. However, the protective effects and underlying mechanisms of AA against DR is not still understood. AIM OF THE STUDY We aimed to investigate whether AA activates AMPK/mTOR/HO-1 regulated autophagy pathway to alleviate DR. MATERIALS AND METHODS In the study, the STZ-induced diabetic model of rats was established, and AA with 10 and 30 mg/kg dosages was given orally for ten weeks to investigate their effect on retinal injury of DR. H2O2-induced ARPE-19 cells were applied to evaluate anti-apoptosis and anti-oxidant effect of AA. RESULTS The results revealed that AA could prevent STZ-induced weight loss and increase the retinal thickness and nuclei counts. The level of HO-1 protein was upregulated both in vivo and in vitro. In addition, AA prevented retinal damage and cell apoptosis through the AMPK-mTOR-regulated autophagy pathway. Furthermore, anti-apoptosis capacity, as well as the expression of HO-1 and LC3 protein, were effectively locked by AMPK inhibitor dorsomorphin dihydrochloride (compound C). CONCLUSIONS This finding implies that AA may be a promising candidate drug by protecting retinal cells from STZ-induced oxidative stress and inflammation through the AMPK/mTOR/HO-1 regulated autophagy pathway.
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Affiliation(s)
- Xuan-Xuan Zhang
- Department of TCMs Pharmaceuticals & Department of Natural Medicinal Chemistry, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 211198, PR China; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China; Department of Endocrinology, Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing, 211200, PR China
| | - Ya-Li Ji
- Department of TCMs Pharmaceuticals & Department of Natural Medicinal Chemistry, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 211198, PR China; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China
| | - Li-Ping Zhu
- Department of TCMs Pharmaceuticals & Department of Natural Medicinal Chemistry, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Zi-Han Wang
- Department of TCMs Pharmaceuticals & Department of Natural Medicinal Chemistry, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 211198, PR China; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China
| | - Chang-Qian Fang
- Department of Endocrinology, Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing, 211200, PR China
| | - Cui-Hua Jiang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China
| | - Ke Pan
- Department of TCMs Pharmaceuticals & Department of Natural Medicinal Chemistry, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 211198, PR China
| | - Jian Zhang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, PR China.
| | - Zhi-Qi Yin
- Department of TCMs Pharmaceuticals & Department of Natural Medicinal Chemistry, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 211198, PR China.
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Alomar SY, M Barakat B, Eldosoky M, Atef H, Mohamed AS, Elhawary R, El-Shafey M, Youssef AM, Elkazaz AY, Gabr AM, Elaskary AA, Salih MAK, Alolayan SO, Zaitone SA. Protective effect of metformin on rat diabetic retinopathy involves suppression of toll-like receptor 4/nuclear factor-k B expression and glutamate excitotoxicity. Int Immunopharmacol 2021; 90:107193. [PMID: 33246827 DOI: 10.1016/j.intimp.2020.107193] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 10/27/2020] [Accepted: 11/08/2020] [Indexed: 01/27/2023]
Abstract
Microvascular complications of diabetes mellitus are progressively significant reasons for mortality. Metformin (MET) is considered as the first-line therapy for type 2 diabetes patients, and may be especially beneficial in cases of diabetic retinopathy although the precise mechanisms of MET action are not fully elucidated. The current study was designed to inspect the antioxidant and modulatory actions of MET on DRET in streptozotocin-induced diabetic rats. The effect of MET on the toll-like receptor 4/nuclear factor kappa B (TLR4/NFkB), inflammatory burden and glutamate excitotoxicity was assessed. Twenty-four male rats were assigned to four experimental groups: (1) Vehicle group, (2) Diabetic control: developed diabetes by injection of streptozotocin (60 mg/kg, i.p.). (3&4) Diabetic + MET group: diabetic rats were left for 9 weeks without treatment and then received oral MET 100 and 200 mg/kg for 6 weeks. Retinal samples were utilized in biochemical, histological, immunohistochemical and electron microscopic studies. MET administration significantly decreased retinal level of insulin growth factor and significantly suppressed the diabetic induced increase of malondialdehyde, glutamate, tumor necrosis factor-α and vascular endothelial growth factor (VEGF). Further, MET decreased the retinal mRNA expression of NFkB, tumor necrosis factor-α and TLR4 in diabetic rats. The current findings shed the light on MET's efficacy as an adjuvant therapy to hinder the development of diabetic retinopathy, at least partly, via inhibition of oxidative stress-induced NFkB/TLR4 pathway and suppression of glutamate excitotoxicity.
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Affiliation(s)
- Suliman Y Alomar
- Doping Research Chair, Department of Zoology, College of Science, King Saud University, Riyadh 11495, Saudi Arabia.
| | - Bassant M Barakat
- Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt; Department of Clinical Pharmacy, College of Clinical Pharmacy, Al-Baha University, Al-Baha, Saudi Arabia
| | - Mohamed Eldosoky
- Department of Neuroscience Technology, College of Applied Sciences, Jubail Imam Abdulrahman bin Faisal University, Saudi Arabia
| | - Hoda Atef
- Department of Histology and Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Abdelaty Shawky Mohamed
- Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Basic Medical Sciences Department, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia
| | - Reda Elhawary
- Department of Pathology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Mohamed El-Shafey
- Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Physiological Sciences Department, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia
| | - Amal M Youssef
- Department of Physiology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Amany Y Elkazaz
- Biochemistry and Molecular Biology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; Biochemistry and Molecular Biology Department, Faculty of Medicine, Portsaid University, Portsaid, Egypt
| | - Attia M Gabr
- Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; Pharmacology and Therapeutics Department, College of Medicine, Qassim University, Qassim, Saudi Arabia
| | | | - Mohamed A K Salih
- Ophthalmology Department, Al-Azher Asyut Faculty of Medicine for Men, Asyut, Egypt
| | - Sultan Othman Alolayan
- Clinical and Hospital Pharmacy Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia
| | - Sawsan A Zaitone
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.
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Evaluation of some oxidative markers in diabetes and diabetic retinopathy. Diabetol Int 2020; 12:108-117. [PMID: 33479586 DOI: 10.1007/s13340-020-00450-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 06/22/2020] [Indexed: 11/27/2022]
Abstract
Aims Diabetes mellitus and diabetic retinopathy (DR) are major public health concerns globally. Oxidative stress plays a central role in the pathogenesis of diabetes and DR. The aim of this study was to investigate the association of malondialdehyde, uric acid and bilirubin with diabetes and diabetic retinopathy development. Methods This study was conducted on 110 diabetics (with and without retinopathy). Beside 40 healthy individuals as a control group. The level of three markers (malondialdehyde, uric acid and bilirubin) was estimated in the studied groups. Receiver operating characteristic analysis and a logistic regression model was performed. Results The present study revealed significantly higher uric acid and malondialdehyde levels, while bilirubin showed significantly lower levels in diabetics compared to control and similarly in diabetic retinopathy compared to those without DR. Furthermore, combination of the three markers increased the accuracy and effect size for differentiation between diabetes with and without DR. In addition, higher levels of uric acid and malondialdehyde were associated with risk of diabetes and DR development. Conclusion This study concluded that higher levels of uric acid and malondialdehyde were associated with increase in the risk of diabetes and DR development, while bilirubin wasn't associated with decreasing the risk of diabetes or DR. However, the combination of malondialdehyde, uric acid and bilirubin may be a valuable addition to the current options for the prognosis of DR. In addition, malondialdehyde may be independent predictor of diabetes and DR as well as uric acid may be used as independent biomarker to predict the risk of DR.
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Effect of diabetes blood-stasis syndrome and Xuefu Zhuyu decoction on ROS-ERK1/2 signaling pathway in rat retina Müller cells. Cytotechnology 2020; 72:303-314. [PMID: 32112164 DOI: 10.1007/s10616-020-00379-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 02/17/2020] [Indexed: 12/20/2022] Open
Abstract
This research aimed to investigate whether diabetic blood-stasis syndrome had a relationship with ROS-ERK1/2 signaling pathway in rat retina Müller cells and explore the effects of traditional Chinese drugs designed for promoting blood circulation to remove blood stasis on diabetic retinopathy (DR) treatment. Immunofluorescence was applied to determine purity of Müller cells. The diabetes was induced in rats by streptozotocin (STZ). Müller cells were stimulated by blood serum obtained from rats with blood-stasis syndrome and then treated by Xuefu Zhuyu decoction. Kits for reactive oxygen species (ROS), superoxide dismutase (SOD) and glutathione (GSH) were used for corresponding detection. Western blot analysis was used to determine the phosphorylation of ERK1/2. The results indicated that stimulation of Müller cells by blood serum of rats with diabetic blood-stasis syndrome increased the expression of ROS, inhibited SOD and GSH, and activated ERK1/2 signaling pathway. Treatment of Xuefu Zhuyu decoction could weaken this phenomenon. What's more, similar effects of ERK1/2 inhibitor U0126 with Xuefu Zhuyu decoction proved the involvement of ERK1/2 signaling pathway. Therefore, our results suggested that traditional Chinese drugs for promoting blood circulation to remove blood stasis would be an effective therapy to treat DR.
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Ramírez-Moreno A, Quintanar Escorza MA, García Garza R, Hady K, Meléndez Valenzuela A, Marszalek JE, Sharara-Núñez I, Delgadillo-Guzmán D. All-trans retinoic acid improves pancreatic cell proliferation on induced type 1 diabetic rats. Fundam Clin Pharmacol 2019; 34:345-351. [PMID: 31762099 DOI: 10.1111/fcp.12523] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 10/26/2019] [Accepted: 11/20/2019] [Indexed: 12/22/2022]
Abstract
All-trans retinoic acid (ATRA) has been extensively studied as an integrating component of endocrine functions in the pancreas. The aim of this study was to evaluate the effects of ATRA on physiopathological biomarkers in an experimental model of rat with type 1 diabetes induced by alloxan (T1D). Twenty Wistar rats were divided equally into five groups, each receiving a different treatment: a control group (CG), a diabetic group without T1D treatment, a diabetic group treated with ATRA, a diabetic group supplemented with vitamin E (VIT E), and a group that was given olive oil (V). The administration of ATRA for 17 days produced a significant reduction in weight and glucose levels, compared to the T1D and VIT E groups. The evaluation of total antioxidant capacity (TAC) and lipoperoxidation showed no relevant difference among the groups. The results of the histological analysis showed similarities both in the size and in the number of islets of Langerhans in the pancreatic tissue obtained from the ATRA group and the CG. ATRA displayed a significant reduction of glycemic values in diabetic rats. Ultrastructurally, ß-cells, acinar, and ductal cells restored their normal appearance. ATRA can contribute to the recovery of pancreatic damage due to alloxan induction. It seems that the antioxidant effect of ATRA is not responsible for the differences observed.
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Affiliation(s)
- Agustina Ramírez-Moreno
- Faculty of Biological Sciences, Autonomous University of Coahuila, Carr. Torreón- Matamoros, km 7.5. C.P.27276, Torreón, Coahuila, Mexico
| | - Martha Angélica Quintanar Escorza
- Department of Biochemistry and Health School of Medicine and Nutrition, Juarez University of the State of Durango, Durango Unit, Durango, Mexico
| | - Rubén García Garza
- Departament of Histology, Faculty of Medicine T.U, Autonomous University of Coahuila, Torreón, Coahuila, Mexico
| | - Keita Hady
- Drug Research Laboratoy, Federal University of Amapá, Rodivia Juscelino Kubitscheck, km 2, Jardim Marco Zero, CEP: 68903-419, Macapa, Amapá, Brazil
| | - Adrian Meléndez Valenzuela
- Department of Pharmacology, Faculty of Medicine, Autonomous University of Coahuila, Torreón Unit, Torreón, Coahuila, Mexico
| | - Jolanta E Marszalek
- Faculty of Biological Sciences, Autonomous University of Coahuila, Carr. Torreón- Matamoros, km 7.5. C.P.27276, Torreón, Coahuila, Mexico
| | - Ibrahim Sharara-Núñez
- Department of Pharmacology, Faculty of Medicine, Autonomous University of Coahuila, Torreón Unit, Torreón, Coahuila, Mexico
| | - Dealmy Delgadillo-Guzmán
- Department of Pharmacology, Faculty of Medicine, Autonomous University of Coahuila, Torreón Unit, Torreón, Coahuila, Mexico
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Tabatabaei-Malazy O, Ardeshirlarijani E, Namazi N, Nikfar S, Jalili RB, Larijani B. Dietary antioxidative supplements and diabetic retinopathy; a systematic review. J Diabetes Metab Disord 2019; 18:705-716. [PMID: 31890694 PMCID: PMC6915253 DOI: 10.1007/s40200-019-00434-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 08/20/2019] [Indexed: 12/11/2022]
Abstract
PURPOSE There is controversial data regarding the effects of dietary antioxidative supplements on diabetic retinopathy (DR). We conducted a systematic review of both observational and randomized controlled clinical trials (RCTs) to clarify whether they are effective or not. METHODS All observational and RCTs conducted by antioxidative supplements on DR published up to 1 January 2018 in PubMed, Web of Sciences, Scopus and Cochrane Library databases were included. Exclusion criteria were animal studies, and studies conducted in Type 1 diabetes mellitus (T1DM), children or pregnant women. Main outcome measures were reporting the incidence or progression of DR in T2DM by assessment of visual fields, and measurements of oxidative and antioxidative biomarkers. The quality of reporting of included articles and risk of bias were assessed. RESULTS Finally, we reached 14 observational studies and 7 RCTs that conducted on 256,259 subjects. Due to severe methodological heterogeneity, only qualitative synthesis was carried. All studies were reported a significantly lower level of antioxidants and higher level of oxidative stress biomarkers in DR compared with others. There was an inverse significant correlation between vitamin C and malondialdehyde (MDA) (r = -0.81) or DNA damage (r = -0.41). These figures were statistically significant between vitamin E and MDA (r = 0.77) or superoxide dismutase (r = 0.44). Coefficient of correlation between MDA and zinc (-0.82), coenzyme Q10 (0.56), and magnesium (-0.73) was significant. Multi-oxidants trials were shown non-significant beneficial effects on DR. CONCLUSIONS Although our study supports the positive effects of antioxidative supplements on DR, more high quality studies are needed to confirm.
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Affiliation(s)
- Ozra Tabatabaei-Malazy
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Nazli Namazi
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Shekoufeh Nikfar
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Personalized Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Evidence-based Evaluation of Cost-Effectiveness and Clinical Outcomes Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy and Pharmaceutical Policy Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Baradar Jalili
- Department of Surgery, University of British Columbia, Vancouver, British Columbia Canada
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Cheng Y, Yu X, Zhang J, Chang Y, Xue M, Li X, Lu Y, Li T, Meng Z, Su L, Sun B, Chen L. Pancreatic kallikrein protects against diabetic retinopathy in KK Cg-A y/J and high-fat diet/streptozotocin-induced mouse models of type 2 diabetes. Diabetologia 2019; 62:1074-1086. [PMID: 30838453 PMCID: PMC6509079 DOI: 10.1007/s00125-019-4838-9] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Accepted: 01/14/2019] [Indexed: 01/06/2023]
Abstract
AIMS/HYPOTHESIS Many studies have shown that tissue kallikrein has effects on diabetic vascular complications such as nephropathy, cardiomyopathy and neuropathy, but its effects on diabetic retinopathy are not fully understood. Here, we investigated the retinoprotective role of exogenous pancreatic kallikrein and studied potential mechanisms of action. METHODS We used KK Cg-Ay/J (KKAy) mice (a mouse model of spontaneous type 2 diabetes) and mice with high-fat diet/streptozotocin (STZ)-induced type 2 diabetes as our models. After the onset of diabetes, both types of mice were injected intraperitoneally with either pancreatic kallikrein (KKAy + pancreatic kallikrein and STZ + pancreatic kallikrein groups) or saline (KKAy + saline and STZ + saline groups) for 12 weeks. C57BL/6J mice were used as non-diabetic controls for both models. We analysed pathological changes in the retina; evaluated the effects of pancreatic kallikrein on retinal oxidative stress, inflammation and apoptosis; and measured the levels of bradykinin and B1 and B2 receptors in both models. RESULTS In both models, pancreatic kallikrein improved pathological structural features of the retina, increasing the thickness of retinal layers, and attenuated retinal acellular capillary formation and vascular leakage (p < 0.05). Furthermore, pancreatic kallikrein ameliorated retinal oxidative stress, inflammation and apoptosis in both models (p < 0.05). We also found that the levels of bradykinin and B1 and B2 receptors were increased after pancreatic kallikrein in both models (p < 0.05). CONCLUSIONS/INTERPRETATION Pancreatic kallikrein can protect against diabetic retinopathy by activating B1 and B2 receptors and inhibiting oxidative stress, inflammation and apoptosis. Thus, pancreatic kallikrein may represent a new therapeutic agent for diabetic retinopathy.
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Affiliation(s)
- Ying Cheng
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital & Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China
| | - Xiaochen Yu
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital & Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China
| | - Jie Zhang
- The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Yunpeng Chang
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital & Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China
| | - Mei Xue
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital & Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China
| | - Xiaoyu Li
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital & Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China
| | - Yunhong Lu
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital & Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China
| | - Ting Li
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital & Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China
| | - Ziyu Meng
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital & Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China
| | - Long Su
- The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Bei Sun
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital & Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China.
| | - Liming Chen
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital & Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China.
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Shahvali S, Shahesmaeili A, Sanjari M, Karami-Mohajeri S. The correlation between blood oxidative stress and sialic acid content in diabetic patients with nephropathy, hypertension, and hyperlipidemia. Diabetol Int 2019; 11:19-26. [PMID: 31950000 DOI: 10.1007/s13340-019-00395-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 04/23/2019] [Indexed: 12/23/2022]
Abstract
This clinical study was designed to find out the correlation between oxidative stress and sialic acid (SA) content of plasma and RBCs in patients with type 2 diabetes. We evaluated SA concentration and oxidative stress biomarkers in healthy subjects and diabetic patients with and without complications in a cross-sectional survey. Significant changes in oxidative stress biomarkers and RBC-SA were revealed in the diabetic patients compared to those in the healthy group. Plasma SA significantly increased with an increase in lipid peroxidation of RBCs (LPO-RBC) (P < 0.001) in the diabetic patients without complication. RBC-SA significantly decreased with an elevation in LPO-RBC (P < 0.001) in all the diabetic patients and those with nephropathy. There was no significant correlation between plasma and RBC-SA and other oxidative stress biomarkers in the diabetic subjects. In multiple logistic regression analysis, RBC-SA was independently related to LPO-RBC in all the diabetic patients and those with nephropathy. We conclude that the induction of LPO-RBC in diabetic patients and those with nephropathy may influence the SA decomposition of RBC membrane, thereby altering its functions and transporter activities. Therefore, LPO-RBC and SA levels in RBCs can be used for prediction of diabetic nephropathy, and further studies to evaluate other factors contributing to desialylation of RBC membrane are justified.
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Affiliation(s)
- Sedigheh Shahvali
- 1Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.,2Pharmaceutics Research Center, Institute of Neuropharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Haft Bagh-e-Alavi Highway, 7616911319 Kerman, Iran
| | - Armita Shahesmaeili
- 3Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Mojgan Sanjari
- 1Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Somayyeh Karami-Mohajeri
- 2Pharmaceutics Research Center, Institute of Neuropharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Haft Bagh-e-Alavi Highway, 7616911319 Kerman, Iran
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Ahmadvand H, Yalameha B, Adibhesami G, Nasri M, Naderi N, Babaeenezhad E, Nouryazdan N. The Protective Role of Gallic Acid Pretreatment On Renal Ischemia-reperfusion Injury in Rats. Rep Biochem Mol Biol 2019; 8:42-48. [PMID: 31334287 PMCID: PMC6590945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2018] [Accepted: 10/14/2018] [Indexed: 06/10/2023]
Abstract
BACKGROUND Renal ischemia-reperfusion injury (RIR) occurs when there is a temporary restriction of blood flow to the kidneys followed by an influx of blood, re-oxygenating the tissues. This occurs as a severe complication of major surgery. This process causes significant damage to the tissues and is responsible for the development of acute kidney injury (AKI), a life-threatening condition with high mortality rates. Here, we evaluated the potential protective effects of the antioxidant, gallic acid (GA), on RIR in an in vivo rat model. METHODS Adult male Sprague Dawley rats were randomly divided into three groups: group 1 (control, n = 8), group 2 (Ischemia-reperfusion (IR) with no-treatment, n = 7), and group 3 (IR + daily GA 100 mg/kg i.p, n = 7). The abdomens of the rats in the control group were opened during the surgical procedure, then sutured closed. GA pretreatment began daily 15 days prior to inducing RIR. To induce RIR, the umbilical arteries were obstructed on both sides and clamped with mild pressure for 45 min. Following the 45 min ischemia, the clamps were removed to allow for the induction of reperfusion. The reperfusion phase was 24 hours. RESULTS Following IR, the serum levels of urea and creatinine significantly increased compared to the controls. Pretreatment with GA was observed to reduce urea and creatinine levels following IR. However, this decrease was not statistically significant. The serum and renal levels of malondialdehyde (MDA) in the IR group was significantly elevated compared to the control group. Conversely, glutathione (GSH) levels and the activity of glutathione peroxidase (GPX) significantly decreased in the IR group compared to controls. Our findings show GA pretreatment to significantly improve the levels of renal MDA, serum GSH, and GPX activity following RIR. CONCLUSION Our findings highlight the protective role for GA in mitigating the damage caused by RIR and its applications as a potential treatment.
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Affiliation(s)
- Hassan Ahmadvand
- Razi Herbal Medicine Research Center, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
- Department of Biochemistry, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
| | - Banafsheh Yalameha
- Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran.
| | - Glavizh Adibhesami
- Department of Biochemistry, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
| | - Maryam Nasri
- Department of Biochemistry, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
| | - Negar Naderi
- Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran.
| | - Esmaeel Babaeenezhad
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Negar Nouryazdan
- Department of Biochemistry, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
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Jin R, Guo Y, Xu B, Wang H, Yuan C. Physicochemical properties of polysaccharides separated from Camellia oleifera Abel seed cake and its hypoglycemic activity on streptozotocin-induced diabetic mice. Int J Biol Macromol 2019; 125:1075-1083. [DOI: 10.1016/j.ijbiomac.2018.12.059] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Revised: 11/27/2018] [Accepted: 12/04/2018] [Indexed: 10/27/2022]
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The Oxidative Stress and Mitochondrial Dysfunction during the Pathogenesis of Diabetic Retinopathy. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:3420187. [PMID: 30254714 PMCID: PMC6145164 DOI: 10.1155/2018/3420187] [Citation(s) in RCA: 152] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 06/27/2018] [Accepted: 08/14/2018] [Indexed: 12/14/2022]
Abstract
Diabetic retinopathy is one of the most serious microvascular complications induced by hyperglycemia via five major pathways, including polyol, hexosamine, protein kinase C, and angiotensin II pathways and the accumulation of advanced glycation end products. The hyperglycemia-induced overproduction of reactive oxygen species (ROS) induces local inflammation, mitochondrial dysfunction, microvascular dysfunction, and cell apoptosis. The accumulation of ROS, local inflammation, and cell death are tightly linked and considerably affect all phases of diabetic retinopathy pathogenesis. Furthermore, microvascular dysfunction induces ischemia and local inflammation, leading to neovascularization, macular edema, and neurodysfunction, ultimately leading to long-term blindness. Therefore, it is crucial to understand and elucidate the detailed mechanisms underlying the development of diabetic retinopathy. In this review, we summarized the existing knowledge about the pathogenesis and current strategies for the treatment of diabetic retinopathy, and we believe this systematization will help and support further research in this area.
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Oral supplementation with melatonin reduces oxidative damage and concentrations of inducible nitric oxide synthase, VEGF and matrix metalloproteinase 9 in the retina of rats with streptozotocin/nicotinamide induced pre-diabetes. Eur J Pharmacol 2018; 833:290-297. [PMID: 29890158 DOI: 10.1016/j.ejphar.2018.06.011] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Revised: 06/06/2018] [Accepted: 06/07/2018] [Indexed: 10/14/2022]
Abstract
Hyperglycemia mediated oxidative stress and pro-angiogenic molecules such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9) are considered important for diabetic retinopathy onset and progression. Melatonin is a pineal hormone that regulates circadian and seasonal rhythms and most likely is involved in regulating glucose metabolism. We aimed to evaluate the potential benefit of melatonin supplementation to the pre-diabetic retina by assessing melatonin effects on lipid peroxidation (thiobarbituric acid reactive substances, TBARS), protein oxidation (advanced oxidation protein products, AOPP) and concentrations of inducible nitric oxide synthase (iNOS), VEGF and MMP9 in the retina of rats with pre-diabetes. Pre-diabetes was induced by streptozotocin (45 mg/kg, i.p.) following nicotinamide injection (110 mg/kg, i.p.). Beside mild hyperglycemia, lower serum insulin, increased fructosamine and lower HDL cholesterol, the present study demonstrated decreased serum melatonin in pre-diabetic rats, as well as, increased concentration of retinal TBARS, AOPP, iNOS, VEGF, and MMP9. Oral supplementation with melatonin (85 μg/animal/day) caused melatonin and HDL cholesterol levels to rise in treated rats and reduced levels of fasting serum glucose and fructosamine. It also affected serum insulin and quantitative insulin sensitivity check index (QUICKI) in treated groups but had no significant effect on non-fasting glucose. Finally, supplementation with melatonin reduced concentrations of TBARS, AOPP, iNOS, VEGF, and MMP9 in significant level, thereby exerting an overall positive effect on oxidative stress and pro-angiogenic signaling in the pre-diabetic retina. Thus, oral melatonin might be considered in an early treatment or in the prevention of retinal changes associated with pre-diabetes.
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Current Advances in Pharmacotherapy and Technology for Diabetic Retinopathy: A Systematic Review. J Ophthalmol 2018; 2018:1694187. [PMID: 29576875 PMCID: PMC5822768 DOI: 10.1155/2018/1694187] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Revised: 10/12/2017] [Accepted: 11/07/2017] [Indexed: 01/01/2023] Open
Abstract
Diabetic retinopathy (DR) is classically defined by its vascular lesions and damage in the neurons of the retina. The cellular and clinical elements of DR have many features of chronic inflammation. Understanding the individual cell-specific inflammatory changes in the retina may lead to novel therapeutic approaches to prevent vision loss. The systematic use of available pharmacotherapy has been reported as a useful adjunct tool to laser photocoagulation, a gold standard therapy for DR. Direct injections or intravitreal anti-inflammatory and antiangiogenesis agents are widely used pharmacotherapy to effectively treat DR and diabetic macular edema (DME). However, their effectiveness is short term, and the delivery system is often associated with adverse effects, such as cataract and increased intraocular pressure. Further, systemic agents (particularly hypoglycemic, hypolipidemic, and antihypertensive agents) and plants-based drugs have also provided promising treatment in the progression of DR. Recently, advancements in pluripotent stem cells technology enable restoration of retinal functionalities after transplantation of these cells into animals with retinal degeneration. This review paper summarizes the developments in the current and potential pharmacotherapy and therapeutic technology of DR. Literature search was done on online databases, PubMed, Google Scholar, clinitrials.gov, and browsing through individual ophthalmology journals and leading pharmaceutical company websites.
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Đorđević B, Sokolović D, Cvetković T, Jevtović-Stoimenov T, Despotović M, Veljković A, Bašić J, Đukić D, Stević N, Veličkov A, Milenković J, Milošević S. EFFECTS OF METFORMIN ON PARAMETERS OF OXIDATIVE DAMAGE IN THE RETINA OF RATS WITH IMPAIRED GLUCOSE TOLERANCE. ACTA MEDICA MEDIANAE 2017. [DOI: 10.5633/amm.2017.0412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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Zhang R, Garrett Q, Zhou H, Wu X, Mao Y, Cui X, Xie B, Liu Z, Cui D, Jiang L, Zhang Q, Xu S. Upregulation of miR-195 accelerates oxidative stress-induced retinal endothelial cell injury by targeting mitofusin 2 in diabetic rats. Mol Cell Endocrinol 2017; 452:33-43. [PMID: 28487236 DOI: 10.1016/j.mce.2017.05.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Revised: 03/24/2017] [Accepted: 05/05/2017] [Indexed: 10/19/2022]
Abstract
This study was performed to investigate the oxidative stress-induced miRNA changes in relation to pathogenesis of diabetic retinopathy (DR) and to establish a functional link between miRNAs and oxidative stress-induced retinal endothelial cell injury. Our results demonstrated that oxidative stress could induce alterations of miRNA expression profile, including up-regulation of miR-195 in the diabetic retina or cultured HMRECs after exposed to H2O2 or HG (P < 0.05). Oxidative stress also resulted in a significant reduction of MFN2 expression in diabetic retina or HMRECs (P < 0.05). Overexpression of miR-195 reduced MFN2 protein levels, and induced tube formation and increased permeability of diabetic retinal vasculature. The luciferase reporter assay confirmed that miR-195 binds to the 3' -untranslated region (3'-UTR) of MFN2 mRNA. This study suggested that miR-195 played a critical role in oxidative stress-induced retinal endothelial cell injury by targeting MFN2 in diabetic rats.
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Affiliation(s)
- Rui Zhang
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China; Burn Engineering Center of Hebei Province, Shijiazhuang, PR China
| | - Qian Garrett
- The University of New South Wales, Sydney, NSW 2052, Australia; The University of Notre Dame Australia, NSW 2008, Australia
| | - Huimin Zhou
- Department of Endocrinology, The First Hospital of Hebei Medical University, Shijiazhuang, PR China; Burn Engineering Center of Hebei Province, Shijiazhuang, PR China.
| | - Xiaoxi Wu
- Department of Endocrinology, The First Hospital of Hebei Medical University, Shijiazhuang, PR China
| | - Yueran Mao
- Department of Endocrinology, The First Hospital of Hebei Medical University, Shijiazhuang, PR China
| | - Ximing Cui
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China
| | - Bing Xie
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China; Burn Engineering Center of Hebei Province, Shijiazhuang, PR China
| | - Zanchao Liu
- Department of Endocrinology, The Second Hospital of Shijiazhuang City, Shijiazhuang, PR China
| | - Dongsheng Cui
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China
| | - Lei Jiang
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China
| | - Qingfu Zhang
- Burn Engineering Center of Hebei Province, Shijiazhuang, PR China
| | - Shunjiang Xu
- Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, PR China; Burn Engineering Center of Hebei Province, Shijiazhuang, PR China.
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Serum bilirubin levels are negatively associated with diabetic retinopathy in patients with type 1 diabetes and normal renal function. Int Ophthalmol 2017; 38:1095-1101. [PMID: 28523523 DOI: 10.1007/s10792-017-0565-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Accepted: 05/10/2017] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Previous studies suggested that total serum bilirubin levels are negatively associated with diabetic retinopathy (DR) and nephropathy in patients with diabetes mellitus. The objective of this study was to explore the relationship between serum total bilirubin levels and prevalence of DR in patients with type 1 diabetes (T1DM) and normal renal function. METHODS Study included 163 T1DM with normal renal function (urinary albumin excretion rate <30 mg/24 h, estimated glomerular filtration rate (eGFR) >60 ml min-11.73 m-2). Photo-documented retinopathy status was made according to the EURODIAB protocol. RESULTS Patients with DR were older (49 vs 42 years, p = 0.001), had higher systolic blood pressure (130 vs 120 mmHg, p = 0.001), triglycerides (0.89 vs 0.77 mmol/L, p = 0.01), and lower serum total bilirubin (12 vs 15 U/L, p = 0.02) and eGFR (100 vs 106 ml min-11.73 m-2, p = 0.03). In multivariate logistic regression analysis, only total serum bilirubin was significantly associated with risk of DR in our subjects (OR 0.88, CI 0.81-0.96, p = 0.006). CONCLUSION These data suggest that serum total bilirubin levels are independently negatively associated with DR in T1DM with normal renal function. Prospective studies are needed to confirm whether lower serum total bilirubin has predictive value for the development of DR in T1DM with normal renal function.
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Chatziralli IP, Theodossiadis G, Dimitriadis P, Charalambidis M, Agorastos A, Migkos Z, Platogiannis N, Moschos MM, Theodossiadis P, Keryttopoulos P. The Effect of Vitamin E on Oxidative Stress Indicated by Serum Malondialdehyde in Insulin-dependent Type 2 Diabetes Mellitus Patients with Retinopathy. Open Ophthalmol J 2017; 11:51-58. [PMID: 28567166 PMCID: PMC5420190 DOI: 10.2174/1874364101711010051] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Revised: 02/16/2017] [Accepted: 03/03/2017] [Indexed: 12/14/2022] Open
Abstract
Background: Several studies have focused on oxidative stress on diabetes mellitus (DM). Our purpose was to investigate the impact of oxidative stress on progression of diabetic retinopathy (DR) in insulin-dependent type 2 DM patients, measuring serum malondialdehyde (MDA), as well as to examine the effect of vitamin E on DR progression in the above-mentioned patients. Methods: Participants in the study were 282 insulin-dependent type 2 DM patients with DR. All participants underwent a thorough ophthalmological examination, so as to grade DR, along with serum MDA measurement. All participants received 300mg vitamin E daily for 3 months and were examined again. Serum MDA pre- and post-intake of Vitamin E was the main outcome. Results: Serum MDA was positively associated with DR stage, while there was a statistically significant difference pre- and post-intake of vitamin E in all DR stages. In a subgroup analysis of patients with proliferative DR, there was a significant difference at baseline between patients who have received prior laser photocoagulation and the treatment naïve patients, while after intake of vitamin E, no statistically significant difference was noticed. Conclusion: Oxidative stress has been found to play significant role in the pathogenesis and progression of DR, while vitamin E seems to reduce MDA levels and subsequent oxidative stress, suggesting that it might have protective role in DR progression.
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Affiliation(s)
| | | | | | | | - Antonios Agorastos
- Department of Internal Medicine, General Hospital of Veroia, Veroia, Greece
| | - Zisis Migkos
- Department of Internal Medicine, General Hospital of Veroia, Veroia, Greece
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Karuppannasamy D, Venkatesan R, Thankappan L, Andavar R, Devisundaram S. Inverse Association between Serum Bilirubin Levels and Retinopathy in Patients with Type 2 Diabetes Mellitus. J Clin Diagn Res 2017; 11:NC09-NC12. [PMID: 28384901 DOI: 10.7860/jcdr/2017/24259.9452] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Accepted: 10/21/2016] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Oxidative stress plays a central role in the pathogenesis of Diabetic Retinopathy (DR) and serum bilirubin has been shown to have antioxidant properties. AIM To investigate the association between serum bilirubin concentration and DR in patients with Type 2 Diabetes Mellitus (DM). MATERIALS AND METHODS This was a hospital based, cross- sectional study where in 86 patients with Type 2 DM and 30 controls were recruited. The study was conducted at a tertiary care centre in Southern India between January 2014 and December 2014. The presence and the severity of DR were determined by fundus examination and grading of colour fundus photographs using the international clinical disease severity scale for DR. Serum total, direct and indirect bilirubin levels were determined in all subjects and the association between bilirubin levels and severity of DR was studied. RESULTS Among the 86 diabetics, 24 had no retinopathy and 62 had DR of varying grades. The mean total bilirubin level among diabetic subjects (0.52±0.17) and controls (0.51±0.19) were found to be similar. The mean total as well as direct bilirubin levels were found to be lower in patients with retinopathy as compared to no retinopathy group (p<0.001). The severity of DR was inversely proportional to the serum bilirubin levels (p=0.010). Serum total bilirubin was found to have a negative association with glycosylated haemoglobin and served as an independent determinant of DR even after adjusting for risk factors known to be associated with DR (p=0.001). CONCLUSION Low serum bilirubin levels are significantly associated with increased risk of DR independent of classic risk factors. Serum bilirubin can serve as a useful biomarker in identifying patients at risk for developing proliferative DR.
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Affiliation(s)
- Divya Karuppannasamy
- Associate Professor, Department of Ophthalmology, PSG Institute of Medical Sciences and Research , Coimbatore, Tamilnadu, India
| | - Raghuram Venkatesan
- Medical Officer, Department of Ophthalmology, Aravind Eye Hospitals , Theni, Tamilnadu, India
| | - Lekha Thankappan
- Assistant Professor, Department of Ophthalmology, PSG Institute of Medical Sciences and Research , Coimbatore, Tamilnadu, India
| | - Raghuram Andavar
- Consultant Vitreoretinal Surgeon, Department of Ophthalmology, PSG Institute of Medical Sciences and Research , Coimbatore, Tamilnadu, India
| | - Sundar Devisundaram
- Professor, Department of Ophthalmology, PSG Institute of Medical Sciences and Research , Coimbatore, Tamilnadu, India
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Tzeng TF, Liu WY, Liou SS, Hong TY, Liu IM. Antioxidant-Rich Extract from Plantaginis Semen Ameliorates Diabetic Retinal Injury in a Streptozotocin-Induced Diabetic Rat Model. Nutrients 2016; 8:nu8090572. [PMID: 27649243 PMCID: PMC5037557 DOI: 10.3390/nu8090572] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Revised: 08/30/2016] [Accepted: 09/01/2016] [Indexed: 02/06/2023] Open
Abstract
Plantaginis semen, the dried ripe seed of Plantago asiatica L. or Plantago depressa Willd. (Plantaginaceae), has been traditionally used to treat blurred vision in Asia. The aim of this work was to investigate the effect of plantaginis semen ethanol extract (PSEE) on the amelioration of diabetic retinopathy (DR) in streptozotocin (STZ)-diabetic rats. PSEE has abundant polyphenols with strong antioxidant activity. PSEE (100, 200 or 300 mg/kg) was oral administrated to the diabetic rats once daily consecutively for 8 weeks. Oral administration of PSEE resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and retinal vascular permeability and leukostasis in diabetic rats. In addition, PSEE administration increased the activities of superoxidase dismutase (SOD) and catalase (CAT), and glutathione peroxidase (GSH) level in diabetic retinae. PSEE treatment inhibited the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) and the phosphorylation of Akt without altering the Akt protein expression in diabetic retinae. PSEE not only down-regulated the gene expression of hypoxia-inducible factor-1α (TNF-α) and interleukin-1β (IL-1β), but also reduced ICAM-1 and VCAM-1 expression in diabetic retinae. Moreover, PSEE reduced the nuclear factor-κB (NF-κB) activation and corrected imbalance between histone deacetylases (HDAC) and histone acetyltransferases (HAT) activities in diabetic retinae. In conclusion, phenolic antioxidants extract from plantaginis semen has potential benefits in the prevention and/or progression of DR.
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Affiliation(s)
- Thing-Fong Tzeng
- Department of Pharmacy and Master Program, Collage of Pharmacy and Health Care, Tajen University, Pingtung County 90741, Taiwan.
| | - Wayne Young Liu
- Department of Urology, Jen-Ai Hospital, Taichung City 41625, Taiwan.
- Center for Basic Medical Science, Collage of Health Science, Central Taiwan University of Science and Technology, Taichung City 40601, Taiwan.
| | - Shorong-Shii Liou
- Department of Pharmacy and Master Program, Collage of Pharmacy and Health Care, Tajen University, Pingtung County 90741, Taiwan.
| | - Tang-Yao Hong
- Department of Biotechnology, Collage of Pharmacy and Health Care, Tajen University, Pingtung County 90741, Taiwan.
| | - I-Min Liu
- Department of Pharmacy and Master Program, Collage of Pharmacy and Health Care, Tajen University, Pingtung County 90741, Taiwan.
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Serum Oxidized LDL Levels in Type 2 Diabetic Patients with Retinopathy in Mthatha Region of the Eastern Cape Province of South Africa. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:2063103. [PMID: 27433285 PMCID: PMC4940560 DOI: 10.1155/2016/2063103] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 05/11/2016] [Accepted: 05/25/2016] [Indexed: 12/19/2022]
Abstract
Oxidized low-density lipoprotein (ox-LDL) is a powerful natural prooxidant derived from native LDL by cell-mediated oxidation. Such oxidation occurs more easily in glycated LDL as observed in diabetes mellitus. We evaluated and compared selected biomarkers of oxidative stress and total antioxidant (TAO) levels in type 2 diabetes mellitus (T2DM) patients with and without retinopathy in the Mthatha region of the Eastern Cape Province, South Africa. The participants totaled to 140 and this number comprised 98 diabetic patients on treatment, stratified by diabetes (54) and diabetes with retinopathy (44). Forty-two nondiabetic healthy controls made up the 140. Fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), lipid profile, serum ox-LDL, thiobarbituric acid reactive substances (TBARS), and TAO levels were measured. A statistically significant increase in FPG, HbA1c, TBARS, and ox-LDL and a significant decrease in TAO levels were seen in T2DM patients with retinopathy as compared to controls. A significant negative correlation was observed between TAO and ox-LDL levels in the diabetic group. In multiple linear regression analyses, duration of diabetes, triglyceride, TAO, and LDL cholesterol were found to be significantly associated with ox-LDL. In multiple logistic regression analyses, ox-LDL [OR 1.02 (1.01–1.03), P = 0.005] was the only risk factor and was significantly associated with the presence of retinopathy.
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SIGNIFICANCE OF ISCHEMIA-MODIFIED ALBUMIN AS A SIMPLE MEASURE OF OXIDATIVE STRESS AND ITS DISCRIMINATORY ABILITY IN DIABETIC RETINOPATHY. Retina 2016; 36:1049-57. [DOI: 10.1097/iae.0000000000001042] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Ye X, Jiang R, Zhang Q, Wang R, Yang C, Ma J, Du H. Increased 8-hydroxy-2'-deoxyguanosine in leukocyte DNA from patients with type 2 diabetes and microangiopathy. J Int Med Res 2016; 44:472-82. [PMID: 27009027 PMCID: PMC5536714 DOI: 10.1177/0300060515621530] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2015] [Accepted: 11/13/2015] [Indexed: 01/10/2023] Open
Abstract
Objective To evaluate oxidative damage in leukocytes from patients with type 2 diabetes by examining 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels. Methods Patients with type 2 diabetes and healthy controls were assessed for demographic, clinical and biochemical characteristics. Levels of 8-OHdG in extracted leukocyte DNA were determined by enzyme linked immunosorbent assay. Results Of 108 patients with type 2 diabetes (56 with microangiopathy, 52 without) and 65 healthy controls, leukocyte 8-OHdG levels were higher in patients with type 2 diabetes versus controls (median ± interquartile range [IQR], 3.19 ± 2.17 versus 0.38 ± 1.00 ng/ml), and higher in patients with type 2 diabetes and microangiopathy versus those without microangiopathy (median ± IQR, 3.34 ± 1.87 versus 2.71 ± 2.26 ng/ml). Patients with type 2 diabetes and microangiopathy had higher serum creatinine and urinary albumin levels versus those without microangiopathy. Leukocyte 8-OHdG levels, duration of type 2 diabetes, albuminuria, use of insulin and use of angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) were independently associated with microangiopathy in patients with type 2 diabetes after adjustment for smoking. Conclusions Leukocyte oxidative DNA damage was high in patients with type 2 diabetes and microangiopathy. Presence of microangiopathy was associated with leukocyte 8-OHdG levels, duration of type 2 diabetes, albuminuria and use of ACE inhibitors/ARBs or insulin.
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Affiliation(s)
- Xiaozhen Ye
- Department of Endocrinology, Jinling Hospital, Southern Medical School, Nanjing, Jiangsu Province, China
| | - Rong Jiang
- Department of Endocrinology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China
| | - Qianqian Zhang
- Department of Endocrinology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China
| | - Ruifeng Wang
- Department of Endocrinology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China
| | - Cuihua Yang
- Department of Endocrinology, Jinling Hospital, Nanjing, Jiangsu Province, China
| | - Jian Ma
- Department of Endocrinology, Jinling Hospital, Nanjing, Jiangsu Province, China
| | - Hong Du
- Department of Endocrinology, Jinling Hospital, Nanjing, Jiangsu Province, China
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Dave A, Kalra P, Gowda BHR, Krishnaswamy M. Association of bilirubin and malondialdehyde levels with retinopathy in type 2 diabetes mellitus. Indian J Endocrinol Metab 2015; 19:373-377. [PMID: 25932393 PMCID: PMC4366776 DOI: 10.4103/2230-8210.152777] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
INTRODUCTION Bilirubin as an antioxidant and malondialdehyde (MDA) as an oxidant have been shown to be associated with various complications of type 2 diabetes mellitus (DM). AIMS AND OBJECTIVES The aim was to measure the levels of serum bilirubin and MDA in type 2 DM patients with and without diabetic retinopathy (DR) and to correlate them with severity of DR. MATERIALS AND METHODS A total number of 120 subjects out of which 40 were controls without type 2 DM and the rest 80 were type 2 DM patients were included in the study. Of those 80 diabetics, 44 patients did not have DR and 36 patients had DR. RESULTS The total bilirubin, direct bilirubin, indirect bilirubin were higher in controls as compared to cases (P = 0.017, 0.033, 0.024). Serum MDA levels were found to be higher in diabetics as compared to controls (P = 0.00). The values of all the three parameters, that is, total bilirubin, direct bilirubin and indirect bilirubin were lower in patients with retinopathy as compared to those without retinopathic changes (P = 0.00, 0.020, and 0.007). Subjects were assigned to quartiles based on serum total bilirubin concentration. The prevalence of DR was significantly lower among persons with the highest bilirubin quartile compared to those with the lowest quartile. The severity of DR was inversely proportional to the total bilirubin levels (P = 0.001). The multiple logistic regression analysis showed total bilirubin to be associated with prevalence of DR (P = 0.035). CONCLUSIONS The levels of total bilirubin were significantly lower in patients with DR and also in the late stages of retinopathy as compared to those without retinopathy and in controls but MDA levels did not show any association with DR.
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Affiliation(s)
- Apoorva Dave
- Department of Endocrinology, M.S. Ramaiah Medical College and Hospitals, Bengaluru, Karnataka, India
| | - Pramila Kalra
- Department of Endocrinology, M.S. Ramaiah Medical College and Hospitals, Bengaluru, Karnataka, India
| | - B. H. Rakshitha Gowda
- Department of Biochemistry, M.S. Ramaiah Medical College and Hospitals, Bengaluru, Karnataka, India
| | - Malavika Krishnaswamy
- Department of Ophthalmology, M.S. Ramaiah Medical College and Hospitals, Bengaluru, Karnataka, India
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Sun L, Zhang Y, Xiong Y. GSTM1 and GSTT1 null genotype and diabetic retinopathy: a meta-analysis. Int J Clin Exp Med 2015; 8:1677-83. [PMID: 25932096 PMCID: PMC4402743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2014] [Accepted: 11/25/2014] [Indexed: 06/04/2023]
Abstract
Glutathione S-transferases (GSTs) have proved to be involved in the detoxifying several oxidants and may play an important role in diabetic retinopathy (DR). Previous studies on the association between glutathione S-transferase T1 (GSTT1) and GSTM1 polymorphism and DR risk reported inconclusive results. To clarify the possible association, we conducted a meta-analysis of eligible studies. We searched in the PubMed, Embase, and Wangfang Medicine databases for studies assessing the association between GSTM1 and GSTT1 null genotype and DR risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association between GSTM1 and GSTT1 null genotype and DR risk. Five studies with 3563 subjects were included in this meta-analysis. The null genotypes of GSTT1 and GSTM1 were associated with a significantly increased risk of DR (OR = 1.69; 95% CI, 1.33-2.16; OR = 1.59; 95% CI, 1.22-2.06), respectively. When stratified by the type of DM, a significantly elevated DR risk was observed in T2DM patients. In conclusion, this meta-analysis suggested that an increased risk of DR was associated with the null polymorphism of GSTT1 and GSTT1, respectively.
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Affiliation(s)
- Li Sun
- Department of Ophthalmology, Huashan Hospital Affiliated to Fudan University Shanghai 200040, China
| | - Yu Zhang
- Department of Ophthalmology, Huashan Hospital Affiliated to Fudan University Shanghai 200040, China
| | - Yitong Xiong
- Department of Ophthalmology, Huashan Hospital Affiliated to Fudan University Shanghai 200040, China
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Sayin N, Kara N, Pekel G. Ocular complications of diabetes mellitus. World J Diabetes 2015; 6:92-108. [PMID: 25685281 PMCID: PMC4317321 DOI: 10.4239/wjd.v6.i1.92] [Citation(s) in RCA: 180] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Revised: 11/22/2014] [Accepted: 12/03/2014] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus (DM) is a important health problem that induces ernestful complications and it causes significant morbidity owing to specific microvascular complications such as, retinopathy, nephropathy and neuropathy, and macrovascular complications such as, ischaemic heart disease, and peripheral vasculopathy. It can affect children, young people and adults and is becoming more common. Ocular complications associated with DM are progressive and rapidly becoming the world's most significant cause of morbidity and are preventable with early detection and timely treatment. This review provides an overview of five main ocular complications associated with DM, diabetic retinopathy and papillopathy, cataract, glaucoma, and ocular surface diseases.
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Ozerkan D, Ozsoy N, Cebesoy S. Response of thymus lymphocytes to streptozotocin-induced diabetes and exogenous vitamin C administration in rats. Microscopy (Oxf) 2014; 63:409-17. [PMID: 25145646 DOI: 10.1093/jmicro/dfu029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Diabetes causes oxidative stress, which in turn generates excessive free radicals resulting in cellular damage. Vitamin C is an antioxidant that protects tissues and organs from oxidative stress. The thymus is one of the most important lymphoid organs, which regulates T-lymphocyte proliferation and maturation. The aim of this study is to investigate the protective effects of vitamin C on the thymus of streptozotocin (STZ)-induced diabetic rats. The mitotic activity and cell integrity of thymic lymphocytes were explored. Wistar Albino rats were divided into three groups: control (Group 1), STZ-diabetes (Group 2) and vitamin C-treated STZ-diabetics (Group 3). Rats received a single intraperitoneal injection of 45 mg/kg STZ to induce diabetes. Vitamin C (20 mg/kg) was administered intragastrically. Semithin and ultrathin sections were examined under a light or an electron microscope, respectively. Considerable numbers of mitotic lymphocytes were observed in the thymus of control rats. In the diabetic rats, however, numbers of mitotic lymphocytes decreased to ∼57% of controls, and cell division abnormalities were observed. Additionally, diabetic rats showed degeneration in the structure of the thymus including trabecular thickening, accumulation of lipid vacuoles, heterochromatic nuclei and loss of mitochondrial cristae. Degradation of medullar and cortical integrity was also detected. In the vitamin C-treated STZ-diabetic group, the structure of the thymus and mitotic activity of the lymphocytes were similar to the control group. These results suggest that vitamin C protects the thymus against injury caused by diabetes and restores thymocyte mitotic activity.
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Affiliation(s)
- Dilşad Ozerkan
- Department of Biology, Faculty of Arts and Sciences, Kastamonu University, 37100, Kastamonu, Turkey
| | - Nesrin Ozsoy
- Department of Biology, Faculty of Science, Ankara University, 06100, Tandogan/Ankara, Turkey
| | - Suna Cebesoy
- Department of Biology, Faculty of Science, Ankara University, 06100, Tandogan/Ankara, Turkey
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Wu Y, Tang L, Chen B. Oxidative stress: implications for the development of diabetic retinopathy and antioxidant therapeutic perspectives. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2014; 2014:752387. [PMID: 25180070 PMCID: PMC4142742 DOI: 10.1155/2014/752387] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Accepted: 07/11/2014] [Indexed: 12/29/2022]
Abstract
In recent decades, localized tissue oxidative stress has been implicated as a key component in the development of diabetic retinopathy (DR). Increasing evidence shows that oxidative stress caused by diabetes-induced metabolic abnormalities is the most common mechanism associated with the pathogenesis of DR for both type 1 and type 2 diabetes. Increase in intracellular reactive oxygen species (ROS) concentrations results in the activation of several mechanisms involved in the pathogenesis of DR. In particular, damage or dysfunction caused by oxidative stress still persists even after glycemia has been normalized. Despite considerable evidence showing the beneficial effects of antioxidants in preventing the development of retinopathy, results from large-scale clinical trials on classic antioxidants are somewhat ambiguous. Scavenging reactive radicals may not be the most ideal antioxidant strategy in DR. Advances in understanding the function of ROS in the development of DR can lead to the development of new therapeutic strategies based on the mechanisms of ROS generation and scavenging. Increasing amounts of data have demonstrated the promising prospect of antioxidant therapy and its beneficial effects in vision protection. Therefore, new strategies that utilize antioxidants as additive therapy should be implemented in the treatment of DR.
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Affiliation(s)
- Ying Wu
- Department of Ophthalmology, Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha 410011, China
| | - Luosheng Tang
- Department of Ophthalmology, Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha 410011, China
| | - Baihua Chen
- Department of Ophthalmology, Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha 410011, China
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Safi SZ, Qvist R, Kumar S, Batumalaie K, Ismail ISB. Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets. BIOMED RESEARCH INTERNATIONAL 2014; 2014:801269. [PMID: 25105142 PMCID: PMC4106080 DOI: 10.1155/2014/801269] [Citation(s) in RCA: 155] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Revised: 05/04/2014] [Accepted: 05/24/2014] [Indexed: 01/09/2023]
Abstract
The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors.
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Affiliation(s)
- Sher Zaman Safi
- Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Rajes Qvist
- Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Selva Kumar
- Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Kalaivani Batumalaie
- Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Ikram Shah Bin Ismail
- Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
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Longo-Mbenza B, Mvitu Muaka M, Masamba W, Muizila Kini L, Longo Phemba I, Kibokela Ndembe D, Tulomba Mona D. Retinopathy in non diabetics, diabetic retinopathy and oxidative stress: a new phenotype in Central Africa? Int J Ophthalmol 2014; 7:293-301. [PMID: 24790873 DOI: 10.3980/j.issn.2222-3959.2014.02.18] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Accepted: 10/14/2013] [Indexed: 11/02/2022] Open
Abstract
AIM To evaluate the rates of retinopathy without diabetes and diabetic retinopathy (DR), associated with some markers of oxidative stress, antioxidants and cardiometabolic risk factors. METHODS We determined the prevalence of DR in 150 type 2 diabetes mellitus (T2DM) patients, that of retinopathy in 50 non diabetics, the levels of body mass index (BMI), waist circumference (WC), blood pressure, lipids, 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), gamma-glutamyl transferase GT (GGT), oxidized low-density lipoprotein (OxLDL), thiobarbituric acid reacting substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), uric acid, creatinine, albumin, total antioxidant status (TAOS), zinc, selenium, magnesium, vitamin C, vitamin D, vitamin E, glucose, apolipoprotein B (ApoB). RESULTS The prevalences of DR at 53y and Rtp at 62y were 44% (n=66) and 10% (n=5), respectively. The highest levels of 8-isoprostane, 8-OHdG, TBARS, SOD, and OxLDL were in DR. The lowest levels of vitamin D, vitamin C, TAOS, and vitamin E were in DR. In the case-control study discriminant analysis, the levels of vitamin C, vitamin D, ApoB, 8-OHdG, creatinine, Zn, vitamin E, and WC distinguished significantly non-diabetics without DR (controls), T2DM patients without DR and T2DM patients with DR. CONCLUSION Anticipation of DR onset is significantly associated with the exageration of oxidative stress biomarkers or decrease of antioxidants in African type 2 diabetics. Prevention of oxidative stress and abdominal obesity is needed. Supplementation in vitamin C, D, and E should be recommended as complement therapies of T2DM.
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Affiliation(s)
- Benjamin Longo-Mbenza
- Walter Sisulu University, Faculty of Health Sciences, Walter Sisulu University, Private Bag X1, Mthatha 5117, South Africa
| | - Moise Mvitu Muaka
- Department of Ophthalmology, University of Kinshasa, Kinshasa 11, DR Congo
| | - Wayiza Masamba
- Department of Chemistry and Chemical Technology, Walter Sisulu University, Private Bag X1, Mthatha 5117, South Africa
| | - Lucien Muizila Kini
- Department of Family Medicine, Umtata General Hospital, Walter Sisulu University, Private Bag X1, Mthatha 5117, South Africa
| | - Igor Longo Phemba
- School of International Studies, Wendzou Medical College, Wenzhou 325005, Zhejiang Province, China
| | | | - Doris Tulomba Mona
- Biostatistics Unit, Lomo Medical Center and Heart of Africa Center of Cardiology, Kinshasa, Kinshasa 11, DR Congo
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