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Dash UC, Nayak V, Navani HS, Samal RR, Agrawal P, Singh AK, Majhi S, Mogare DG, Duttaroy AK, Jena AB. Understanding the molecular bridges between the drugs and immune cell. Pharmacol Ther 2025; 267:108805. [PMID: 39908660 DOI: 10.1016/j.pharmthera.2025.108805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 01/11/2025] [Accepted: 01/21/2025] [Indexed: 02/07/2025]
Abstract
The interactions of drugs with the host's immune cells determine the drug's efficacy and adverse effects in patients. Nonsteroidal Anti-Inflammatory Drugs (NSAID), such as corticosteroids, NSAIDs, and immunosuppressants, affect the immune cells and alter the immune response. Molecularly, drugs can interact with immune cells via cell surface receptors, changing the antigen presentation by modifying the co-stimulatory molecules and interacting with the signaling pathways of T cells, B cells, Natural killer (NK) cells, mast cells, basophils, and macrophages. Immunotoxicity, resulting from drug-induced changes in redox status, generation of Reactive Oxygen Species (ROS)/Reactive Nitrogen Species (RNS), and alterations in antioxidant enzymes within immune cells, leads to immunodeficiency. This, in turn, causes allergic reactions, autoimmune diseases, and cytokine release syndrome (CRS). The treatment options should include the evaluation of immune status and utilization of the concept of pharmacogenomics to minimize the chances of immunotoxicity. Many strategies in redox, like targeting the redox pathway or using redox-active agents, are available for the modulation of the immune system and developing drugs. Case studies highlight significant drug-immune cell interactions and patient outcomes, underscoring the importance of understanding these complexities. The future direction focuses on the drugs to deliver antiviral therapy, new approaches to immunomodulation, and modern technologies for increasing antidote effects with reduced toxicity. In conclusion, in-depth knowledge of the interaction between drugs and immune cells is critical to protect the patient from the adverse effects of the drug and improve therapeutic outcomes of the treatment process. This review focuses on the multifaceted interactions of drugs and their consequences at the cellular levels of immune cells.
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Affiliation(s)
- Umesh Chandra Dash
- School of Biotechnology, Campus 11, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Bhubaneswar, Odisha 751024, India
| | - Vinayak Nayak
- Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy 502284, India
| | - Hiten Shanker Navani
- Biological Materials Laboratory, CSIR- Central Leather Research Institute, Adyar, Chennai 600020, India
| | - Rashmi Rekha Samal
- CSIR-Institute of Minerals & Materials Technology, Bhubaneswar 751 013, India
| | - Palak Agrawal
- Unit de Microbiologie Structurale, Institut Pasteur, Paris, France
| | - Anup Kumar Singh
- National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune, India
| | - Sanatan Majhi
- Post Graduate Department of Biotechnology, Utkal University, Bhubaneswar 751004, Odisha, India
| | - Devraj Ganpat Mogare
- National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune, India
| | - Asim K Duttaroy
- Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway.
| | - Atala Bihari Jena
- National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune, India
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Luo T, Wang B, Chen R, Qi Q, Wu R, Xie S, Chen H, Han J, Wu D, Cao S. Research progress of nitroxide radical-based MRI contrast agents: from structure design to application. J Mater Chem B 2025; 13:372-398. [PMID: 39565110 DOI: 10.1039/d4tb02272f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2024]
Abstract
Magnetic resonance imaging (MRI) remains a cornerstone of diagnostic imaging, offering unparalleled insights into anatomical structures and pathological conditions. Gadolinium-based contrast agents have long been the standard in MRI enhancement, yet concerns over nephrogenic systemic fibrosis have spurred interest in metal-free alternatives. Nitroxide radical-based MRI contrast agents (NO-CAs) have emerged as promising candidates, leveraging their biocompatibility and imaging capabilities. This review summaries the latest advancements in NO-CAs, focusing on synthesis methodologies, influencing effects of structures of NO-CAs on relaxation efficiency and their applications across various clinical contexts. Comprehensive discussions encompass small molecular, polymeric, and nano-sized NO-CAs, detailing their unique properties and potential clinical utilities. Despite challenges, NO-CAs represent a dynamic area of research poised to revolutionize MRI diagnostics. This review serves as a critical resource for researchers and practitioners seeking to navigate the evolving landscape of MRI contrast agents.
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Affiliation(s)
- Tao Luo
- School of Biomedical Engineering, Sun Yat-Sen University of Shenzhen Campus, Shenzhen, China.
| | - Bo Wang
- School of Biomedical Engineering, Sun Yat-Sen University of Shenzhen Campus, Shenzhen, China.
| | - Runxin Chen
- Shenzhen University General Hospital, Shenzhen, China
| | - Qi Qi
- Shenzhen University General Hospital, Shenzhen, China
| | - Ruodai Wu
- Shenzhen University General Hospital, Shenzhen, China
| | - Shunzi Xie
- School of Biomedical Engineering, Sun Yat-Sen University of Shenzhen Campus, Shenzhen, China.
| | - Hanbing Chen
- School of Biomedical Engineering, Sun Yat-Sen University of Shenzhen Campus, Shenzhen, China.
| | - Jialei Han
- School of Biomedical Engineering, Sun Yat-Sen University of Shenzhen Campus, Shenzhen, China.
| | - Dalin Wu
- School of Biomedical Engineering, Sun Yat-Sen University of Shenzhen Campus, Shenzhen, China.
- Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, Sun Yat-Sen University, Shenzhen, China
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de Sousa DP, de Assis Oliveira F, Arcanjo DDR, da Fonsêca DV, Duarte ABS, de Oliveira Barbosa C, Ong TP, Brocksom TJ. Essential Oils: Chemistry and Pharmacological Activities-Part II. Biomedicines 2024; 12:1185. [PMID: 38927394 PMCID: PMC11200837 DOI: 10.3390/biomedicines12061185] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 05/17/2024] [Accepted: 05/20/2024] [Indexed: 06/28/2024] Open
Abstract
The importance of essential oils and their components in the industrial sector is attributed to their chemical characteristics and their application in the development of products in the areas of cosmetology, food, and pharmaceuticals. However, the pharmacological properties of this class of natural products have been extensively investigated and indicate their applicability for obtaining new drugs. Therefore, this review discusses the use of these oils as starting materials to synthesize more complex molecules and products with greater commercial value and clinic potential. Furthermore, the antiulcer, cardiovascular, and antidiabetic mechanisms of action are discussed. The main mechanistic aspects of the chemopreventive properties of oils against cancer are also presented. The data highlight essential oils and their derivatives as a strategic chemical group in the search for effective therapeutic agents against various diseases.
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Affiliation(s)
| | | | - Daniel Dias Rufino Arcanjo
- LAFMOL—Laboratory of Functional and Molecular Studies in Physiopharmacology, Department of Biophysics and Physiology, Federal University of Piaui, Teresina 64049-550, Brazil; (D.D.R.A.); (C.d.O.B.)
| | - Diogo Vilar da Fonsêca
- Collegiate of Medicine, Federal University of São Francisco Valley, Bahia 48607-190, Brazil;
| | - Allana Brunna S. Duarte
- Laboratory of Pharmaceutical Chemistry, Federal University of Paraíba, João Pessoa 58051-900, Brazil;
| | - Celma de Oliveira Barbosa
- LAFMOL—Laboratory of Functional and Molecular Studies in Physiopharmacology, Department of Biophysics and Physiology, Federal University of Piaui, Teresina 64049-550, Brazil; (D.D.R.A.); (C.d.O.B.)
| | - Thomas Prates Ong
- Department of Food Science and Nutrition, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo 05508-000, Brazil;
- Food Research Center (FoRC), University of São Paulo, São Paulo 05508-000, Brazil
| | - Timothy John Brocksom
- Department of Chemistry, Federal University of São Carlos, São Carlos 13565-905, Brazil;
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Heeba GH, Morsy MA, Mahmoud ME, Abdel-Latif R. Gastro-protective effect of l-arginine against nitric oxide deficiency-related mucosal injury induced by indomethacin: Does age matter? J Biochem Mol Toxicol 2023; 37:e23479. [PMID: 37483153 DOI: 10.1002/jbt.23479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 07/09/2023] [Accepted: 07/13/2023] [Indexed: 07/25/2023]
Abstract
Gastric ulcer is a common disease with increased prevalence in the aged population. Aged gastric mucosa has increased susceptibility to injury along with nonsteroidal anti-inflammatory drugs use due to impaired mucosal defense and decreased vasodilator release. We investigated whether l-arginine could protect against age-related gastric ulceration induced by indomethacin. Aged and adult male Wistar rats were administered sole and combined treatment of l-arginine and Nω -nitro-l-arginine methyl ester ( l-NAME) before induction of gastric ulceration by indomethacin. The gastroprotective effect of l-arginine was displayed only in adult rats with indomethacin-induced gastric ulceration, as evidenced by a significant decrease in ulcer index, oxidative stress parameters, and mucosal myeloperoxidase activity along with increased mucosal PGE2 levels. Interestingly, the mucosal gene expressions of NF-кB, iNOS, and COX-2 were significantly suppressed by l-arginine pretreatment and aggregated upon pretreatment with l-NAME in both adult and aged rats treated with indomethacin. In conclusion, l-arginine protected the rats' gastric mucosa against indomethacin-induced gastric ulceration, possibly, at least in part, by enhancement of mucosal nitric oxide/PGE2 content along with suppressing gastric inflammation and oxidative stress. This study supposed that the gastroprotective effect of l-arginine depends on aging, and even so, the adoption of a new approach to gastric ulcer treatment for the aged population is warranted.
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Affiliation(s)
- Gehan H Heeba
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, Egypt
| | - Mohamed A Morsy
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
- Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt
| | - Magda E Mahmoud
- Department of Agricultural Chemistry, Faculty of Agriculture, Minia University, El-Minia, Egypt
| | - Rania Abdel-Latif
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, Egypt
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Hermes TDA, Mâncio RD, Mizobutti DS, Macedo AB, Kido LA, Cagnon Quitete VHA, Minatel E. Cilostazol attenuates oxidative stress and apoptosis in the quadriceps muscle of the dystrophic mouse experimental model. Int J Exp Pathol 2023; 104:13-22. [PMID: 36565167 PMCID: PMC9845609 DOI: 10.1111/iep.12461] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 10/04/2022] [Accepted: 10/18/2022] [Indexed: 12/25/2022] Open
Abstract
Duchenne muscular dystrophy (DMD) is the most severe and frequent form of muscular dystrophy. The mdx mouse is one of the most widely used experimental models to understand aspects of the biology of dystrophic skeletal muscles and the mechanisms of DMD. Oxidative stress and apoptosis are present in early stages of the disease in mdx mice. The high production of reactive oxygen species (ROS) causes activation of apoptotic death regulatory proteins due to DNA damage and breakdown of nuclear and mitochondrial membranes. The quadriceps (QUA) muscle of the mdx mouse is a good tool to study oxidative events. Previous studies have demonstrated that cilostazol exerts an anti-oxidant effect by decreasing the production of reactive oxygen species (ROS). The present study aimed to evaluate the ability of cilostazol to modulate oxidative stress and apoptosis in the QUA muscle of mdx mice. Fourteen-day-old mdx mice received cilostazol or saline for 14 days. C57BL/10 mice were used as a control. In the QUA muscle of mdx mice, cilostazol treatment decreased ROS production (-74%), the number of lipofuscin granules (-47%), lipid peroxidation (-11%), and the number of apoptotic cells (-66%). Thus cilostazol showed anti-oxidant and anti-apoptotic action in the QUA muscle of mdx mice.
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Affiliation(s)
- Túlio de Almeida Hermes
- Department of Structural and Functional Biology, Institute of BiologyState University of Campinas (UNICAMP)São PauloBrazil
- Departament of Anatomy, Institute of Biomedical SciencesFederal University of Alfenas (UNIFAL‐MG)AlfenasBrazil
| | - Rafael Dias Mâncio
- Department of Structural and Functional Biology, Institute of BiologyState University of Campinas (UNICAMP)São PauloBrazil
| | - Daniela Sayuri Mizobutti
- Department of Structural and Functional Biology, Institute of BiologyState University of Campinas (UNICAMP)São PauloBrazil
| | - Aline Barbosa Macedo
- Department of Structural and Functional Biology, Institute of BiologyState University of Campinas (UNICAMP)São PauloBrazil
| | - Larissa Akemi Kido
- Department of Structural and Functional Biology, Institute of BiologyState University of Campinas (UNICAMP)São PauloBrazil
| | | | - Elaine Minatel
- Department of Structural and Functional Biology, Institute of BiologyState University of Campinas (UNICAMP)São PauloBrazil
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Shinu P, Sharma M, Gupta GL, Mujwar S, Kandeel M, Kumar M, Nair AB, Goyal M, Singh P, Attimarad M, Venugopala KN, Nagaraja S, Telsang M, Aldhubiab BE, Morsy MA. Computational Design, Synthesis, and Pharmacological Evaluation of Naproxen-Guaiacol Chimera for Gastro-Sparing Anti-Inflammatory Response by Selective COX2 Inhibition. Molecules 2022; 27:molecules27206905. [PMID: 36296501 PMCID: PMC9609004 DOI: 10.3390/molecules27206905] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 10/07/2022] [Accepted: 10/10/2022] [Indexed: 11/24/2022] Open
Abstract
The 4-allyl guaiacol is a natural phenolic molecule that has been widely studied for its antioxidant capacity against reactive-oxygen-species-mediated cellular damage. Therefore, we hypothesized that concomitant use of an antioxidant and NSAID may decrease the risk of gastrointestinal toxicity and make the therapy safer. To address the gastrointestinal toxicity of conventional NSAIDs, a new S-naproxen-4-allyl guaiacol chimera (MAS-1696) was computationally developed, chemically synthesized, and tested for anti-inflammatory effectiveness and gastrointestinal safety. The inhibitory potency of MAS-1696 tested against cyclooxygenase-2 (COX2), 15-lipoxygenase-2 (15-LOX2), and lipoxygenase-5 (5-LOX) in vitro revealed a stronger inhibition of COX2. Furthermore, the MAS-1696 chimera increased the COX selectivity index by 23% as compared to the parent compound naproxen, implying higher efficacy and gastric safety. In vivo data showed that MAS-1696 was less likely to cause gastrointestinal harm than naproxen while also exerting anti-inflammatory and analgesic effects equivalent to or superior to naproxen. In conclusion, MAS-1696 is orally active, bio-labile, and crystalline, making it a medication that may be administered orally.
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Affiliation(s)
- Pottathil Shinu
- Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
- Correspondence: (P.S.); (M.S.); Tel.: +966-551732794 (P.S.)
| | - Manu Sharma
- Department of Chemistry, National Forensic Sciences University Delhi Campus, New Delhi 110085, India
- Correspondence: (P.S.); (M.S.); Tel.: +966-551732794 (P.S.)
| | - Girdhari Lal Gupta
- Department of Pharmacology, School of Pharmacy and Technology Management, SVKM’s NMIMS University, Shirpur 425405, India
| | - Somdutt Mujwar
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, India
| | - Mahmoud Kandeel
- Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Manish Kumar
- M.M College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Ambala 133201, India
| | - Anroop B. Nair
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Manoj Goyal
- Department of Anesthesia Technology, College of Applied Medical Sciences in Jubail, Imam Abdul Rahman Bin Faisal University, Jubail 35816, Saudi Arabia
| | - Purna Singh
- Department of Physiology, College of Medicine, Saint James School of Medicine, The Valley 3872, Anguilla
| | - Mahesh Attimarad
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Katharigatta N. Venugopala
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
- Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban 4000, South Africa
| | - Sreeharsha Nagaraja
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
- Department of Pharmaceutical Chemistry, Vidya Siri College of Pharmacy, Off Sarjapura Road, Bangalore 560035, India
| | - Mallikarjun Telsang
- Department of Surgery, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Bandar E. Aldhubiab
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Mohamed A. Morsy
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
- Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt
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Beta-caryophyllene as an antioxidant, anti-inflammatory and re-epithelialization activities in a rat skin wound excision model. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:9004014. [PMID: 35154574 PMCID: PMC8831077 DOI: 10.1155/2022/9004014] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 01/13/2022] [Indexed: 12/14/2022]
Abstract
The skin is a critical organ for the maintenance of the integrity and protection of the organism. When a wound occurs, a sequence of healing mechanisms is triggered to reconstruct the wounded area. β-caryophyllene is a sesquiterpene in Copaifera langsdorffii oleoresin with antioxidant and anti-inflammatory potential. On the basis of previous studies with C. langsdorffii, β-caryophyllene was selected to evaluate its wound healing potential and pharmacological mechanisms. The excision wound model was used with male Wistar rats and macroscopic, histological, immunohistochemical and biochemical analyses were performed with skin samples, comparing the β-caryophyllene-treated group with reference drugs. The results showed macroscopic retraction of the wounds treated with β-caryophyllene. Biochemical assays revealed the antioxidant and anti-inflammatory mechanisms of the β-caryophyllene-treated group with increasing levels of IL-10 and GPx and decreasing levels of pro-inflammatory molecules, including TNF-α, IFN-γ, IL-1β and IL-6. After β-caryophyllene treatment, immunohistochemical assays showed enhanced re-epithelialization, through the increase in laminin-γ2 and desmoglein-3 immunolabeling. β-caryophyllene also act in the remodeling mechanism, increasing the collagen content in the Masson’s trichrome staining. These findings indicated the wound-healing potential of β-caryophyllene topical formulation in rat skin wounds, mediated by antioxidant, anti-inflammatory and re-epithelialization mechanisms.
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Yasukawa K. Redox-Based Theranostics of Gastric Ulcers Using Nitroxyl Radicals. Antioxid Redox Signal 2022; 36:160-171. [PMID: 34498915 DOI: 10.1089/ars.2021.0104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Significance: Redox-based theranostics involves redox monitoring and therapeutics that normalize redox imbalance. It may be a promising approach to markedly improve a patient's quality of life through streamlined treatment. Nitroxyl radicals are useful for both redox monitoring and treating gastric ulcers in rodents. Recent Advances: Redox monitoring using in vivo electron paramagnetic resonance (EPR) spectroscopy in a gastric ulcer rat model showed the production of reactive oxygen species in the whole stomach. A combination of Overhauser-enhanced magnetic resonance imaging (MRI) and nitroxyl radicals provided high-resolution images of redox imbalance in the stomach of rats with a gastric ulcer. Treatment with nitroxyl radicals was effective to treat ulcers that were formed using model experiments of Helicobacter pylori and mental stress as well as nonsteroidal anti-inflammatory drugs. Critical Issues: For redox monitoring using Overhauser-enhanced MRI, the EPR irradiation power that is delivered to subjects must be within the range of the specific absorption rate regulation to protect against microwave damage regardless of a decrease in image contrast. The effect of long-term treatment with a nitroxyl radical in patients with a gastric ulcer remains unclear. Future Directions: Further research on redox-based theranostics in redox-related diseases, including gastric ulcers, would be accelerated by improving the redox imager and by developing functional nitroxyl radicals that localize in the target organ, tissue, or cell and that have specific reactivity for the redox-related biomolecule.
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Affiliation(s)
- Keiji Yasukawa
- Laboratory of Advanced Pharmacology, Faculty of Pharmaceutical Sciences, Daiichi University of Pharmacy, Fukuoka, Japan
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Chemoprevention with a tea from hawthorn ( Crataegus oxyacantha) leaves and flowers attenuates colitis in rats by reducing inflammation and oxidative stress. FOOD CHEMISTRY-X 2021; 12:100139. [PMID: 34712949 PMCID: PMC8531563 DOI: 10.1016/j.fochx.2021.100139] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 10/01/2021] [Accepted: 10/04/2021] [Indexed: 12/19/2022]
Abstract
A tea from the leaves and flowers of hawthorn is rich in flavonoids, especially vitexin-2-O-rhamnoside. Mesalamine and hawthorn tea have positive healing effects in rats with colitis. Hawthorn tea reduces the length and area of the brownish necrotic lesions. Hawthorn tea diminishes the levels of the inflammatory markers MPO and IL-1β. Hawthorn tea regulates the activity of the oxidative stress enzymes CAT and GR. The purpose of the study was to determine the effects of a tea from the leaves and flowers of Crataegus oxyacantha in rats with colitis. Colitis was induced by administration of 2,4,6-trinitrobenzene sulfonic acid. Hawthorn tea (HT) (100 mg/kg) was given via gavage for 21 days and the mesalamine drug (100 mg/kg) was administrated during the period of disease onset. HT was rich in total phenolic compounds (16.5%), flavonoids (1.8%), and proanthocyanidins (1.5%); vitexin-2-O-rhamnoside was the main compound detected. Mesalamine and the HT diminished the length of the lesions formed in the colon, in addition to reducing the levels of myeloperoxidase and interleukin-1β. Mesalamine was able to significantly reverse the body weight loss, while HT improved the activity of glutathione reductase and catalase. Histological scoring was not changed by the interventions, but it was highly correlated with the necrotic area. HT given at 100 mg/kg can be effective against colitis.
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Key Words
- CAT, Catalase
- CD, Crohn’s disease
- Colon
- Crataegus oxyacantha
- DAD, Diode array detection
- DAI, Disease Activity Index
- DSS, Dextran sodium sulfate
- ELISA, Enzyme-linked immunosorbent assay
- ESI, Electrospray ionization
- FID, Flame ionization detector
- FRAP, Ferric reducing antioxidant power
- GC, Gas chromatograph
- GPx, glutathione peroxidase
- GR, Glutathione reductase
- GSH, Glutathione
- HT, Hawthorn tea
- IBD, Inflammatory bowel disease
- IL-1β, Interleukin-1beta
- Inflammatory bowel diseases
- MDA, Malondialdehyde
- MPO, Myeloperoxidase
- MS, Mass spectrometry
- ORAC, Oxygen-radical absorbing capacity
- Polyphenol
- SCFA, Short-chain fatty acid
- SOD, Superoxide dismutase
- TFC, Total flavonoids content
- TNBS, 2,4,6-trinitrobenzene sulfonic acid
- TNF-α, Tumor necrosis factor-alpha
- TPC, Total polyphenols content
- TPOC, Total proanthocyanidin oligomers content
- UC, Ulcerative colitis
- UHPLC, Ultra-high-performance liquid chromatography
- Vitexin-2-O-rhamnoside
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Yi Z, Zhang M, Ma Z, Tuo B, Liu A, Deng Z, Zhao Y, Li T, Liu X. Role of the posterior mucosal defense barrier in portal hypertensive gastropathy. Biomed Pharmacother 2021; 144:112258. [PMID: 34614465 DOI: 10.1016/j.biopha.2021.112258] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 09/24/2021] [Accepted: 09/26/2021] [Indexed: 12/15/2022] Open
Abstract
Portal hypertensive gastropathy (PHG) is a complication of cirrhotic or noncirrhotic portal hypertension. PHG is very important in the clinic because it can cause acute or even massive blood loss, and its treatment efficacy and prognosis are poor. Currently, the incidence of PHG in patients with cirrhosis is 20-80%, but its pathogenesis is complicated and poorly understood. Studies have shown that portal hypertension can cause changes in gastric mucosal microcirculation hemodynamics, leading to changes in gastric mucosal histology and function and thereby weakening the mucosal defense barrier. However, no specific drug treatment plans are currently available. This article reviews the current literature to further our understanding of the mechanism underlying PHG and the relationship between PHG and the posterior mucosal defense barrier and to explore new therapeutic targets.
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Affiliation(s)
- Zhiqiang Yi
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China; Department of Gastroenterology, Fuling Central Hospital of Chongqing City, Chongqing, China
| | - Minglin Zhang
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Zhiyuan Ma
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China; Digestive Disease Institute of Guizhou Province, Zunyi, Guizhou Province, China; Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Biguang Tuo
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China; Digestive Disease Institute of Guizhou Province, Zunyi, Guizhou Province, China
| | - Aimin Liu
- Department of Gastroenterology, Fuling Central Hospital of Chongqing City, Chongqing, China
| | - Zilin Deng
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Yingying Zhao
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Taolang Li
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China.
| | - Xuemei Liu
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China; Digestive Disease Institute of Guizhou Province, Zunyi, Guizhou Province, China.
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Rozza AL, Beserra FP, Vieira AJ, Oliveira de Souza E, Hussni CA, Martinez ERM, Nóbrega RH, Pellizzon CH. The Use of Menthol in Skin Wound Healing-Anti-Inflammatory Potential, Antioxidant Defense System Stimulation and Increased Epithelialization. Pharmaceutics 2021; 13:pharmaceutics13111902. [PMID: 34834317 PMCID: PMC8620938 DOI: 10.3390/pharmaceutics13111902] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 11/02/2021] [Accepted: 11/03/2021] [Indexed: 12/17/2022] Open
Abstract
Wound healing involves inflammatory, proliferative, and remodeling phases, in which various cells and chemical intermediates are involved. This study aimed to investigate the skin wound healing potential of menthol, as well as the mechanisms involved in its effect, after 3, 7, or 14 days of treatment, according to the phases of wound healing. Skin wound was performed in the back of Wistar rats, which were topically treated with vehicle cream; collagenase-based cream (1.2 U/g); or menthol-based cream at 0.25%, 0.5%, or 1.0% over 3, 7, or 14 days. Menthol cream at 0.5% accelerated the healing right from the inflammatory phase (3 days) by decreasing mRNA expression of inflammatory cytokines TNF-α and Il-6. At the proliferative phase (7 days), menthol 0.5% increased the activity of antioxidant enzymes SOD, GR, and GPx, as well as the level of GSH, in addition to decreasing the levels of inflammatory cytokines TNF-α, IL-6, and IL-1β and augmenting mRNA expression for Ki-67, a marker of cellular proliferation. At the remodeling phase (14 days), levels of inflammatory cytokines were decreased, and the level of Il-10 and its mRNA expression were increased in the menthol 0.5% group. Menthol presented skin wound healing activity by modulating the antioxidant system of the cells and the inflammatory response, in addition to stimulating epithelialization.
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Affiliation(s)
- Ariane Leite Rozza
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil; (F.P.B.); (A.J.V.); (E.O.d.S.); (E.R.M.M.); (R.H.N.); (C.H.P.)
- Correspondence:
| | - Fernando Pereira Beserra
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil; (F.P.B.); (A.J.V.); (E.O.d.S.); (E.R.M.M.); (R.H.N.); (C.H.P.)
| | - Ana Júlia Vieira
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil; (F.P.B.); (A.J.V.); (E.O.d.S.); (E.R.M.M.); (R.H.N.); (C.H.P.)
| | - Eduardo Oliveira de Souza
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil; (F.P.B.); (A.J.V.); (E.O.d.S.); (E.R.M.M.); (R.H.N.); (C.H.P.)
| | - Carlos Alberto Hussni
- Department of Surgery and Veterinary Anesthesiology, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Dr. Walter M Correa Street, Botucatu 18618-689, Brazil;
| | - Emanuel Ricardo Monteiro Martinez
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil; (F.P.B.); (A.J.V.); (E.O.d.S.); (E.R.M.M.); (R.H.N.); (C.H.P.)
| | - Rafael Henrique Nóbrega
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil; (F.P.B.); (A.J.V.); (E.O.d.S.); (E.R.M.M.); (R.H.N.); (C.H.P.)
| | - Cláudia Helena Pellizzon
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil; (F.P.B.); (A.J.V.); (E.O.d.S.); (E.R.M.M.); (R.H.N.); (C.H.P.)
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El Menyiy N, Guaouguaou FE, El Baaboua A, El Omari N, Taha D, Salhi N, Shariati MA, Aanniz T, Benali T, Zengin G, El-Shazly M, Chamkhi I, Bouyahya A. Phytochemical properties, biological activities and medicinal use of Centaurium erythraea Rafn. JOURNAL OF ETHNOPHARMACOLOGY 2021; 276:114171. [PMID: 33940085 DOI: 10.1016/j.jep.2021.114171] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 04/01/2021] [Accepted: 04/24/2021] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Centaurium erythraea is an important medicinal plant in many countries, e.g. Morocco, Algeria, Italy, Spain, Portugal, and countries of Balkan Peninsula. It is used in folk medicine to treat various illnesses. It is also used as an antiapoplectic, anticoagulant, anticholagogue, antipneumonic, hematocathartic, and as a hypotensive agent. AIM OF THE REVIEW In this review, previous reports on the taxonomy, botanical description, geographic distribution, ethnomedicinal applications, phytochemistry, pharmacological properties, and toxicity of Centaurium erythraea were critically summarized. MATERIALS AND METHODS Scientific search engines including PubMed, ScienceDirect, SpringerLink, Web of Science, Scopus, Wiley Online, SciFinder, and Google Scholar were consulted to collect data on C. erythraea. The data presented in this work summarized the main reports on C. erythraea phytochemical compounds, ethnomedicinal uses, and pharmacological activities. RESULTS C. erythraea is used in traditional medicine to treat various diseases such as diabetes, fever, rhinitis, stomach ailments, urinary tract infections, dyspeptic complaints, loss of appetite, and hemorrhoids, and as diuretic. The essential oils and extracts of C. erythraea exhibited numerous biological properties such as antibacterial, antioxidant, antifungal, antileishmanial, anticancer, antidiabetic, anti-inflammatory, insecticidal, diuretic, gastroprotective, hepatoprotective, dermatoprotective, neuroprotective, and inhibitory agent for larval development. Phytochemical characterization of C. erythraea revealed the presence of several classes of secondary metabolites such as xanthonoids, terpenoids, flavonoids, phenolic acids, and fatty acids. CONCLUSIONS Ethnomedicinal studies demonstrated the use of C. erythraea for the treatment of various disorders. Pharmacological reports showed that C. erythraea especially its aerial parts and roots exhibited potent, and beneficial activities. These findings confirmed the link between the traditional medicinal use and the results of the scientific biological experiments. Considering these results, further investigation using diverse in vivo pharmacological assays are strongly recommended to validate the results of its traditional use. Toxicological tests and pharmacokinetic studies are also required to validate the safety and efficacy of C. erythraea and its bioactive contents.
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Affiliation(s)
- Naoual El Menyiy
- Laboratory of Natural Substances, Pharmacology, Environment, Modeling, Health and Quality of Life (SNAMOPEQ), Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
| | - Fatima-Ezzahrae Guaouguaou
- Mohammed V University in Rabat, LPCMIO, Materials Science Center (MSC), Ecole Normale Supérieure, Rabat, Morocco.
| | - Aicha El Baaboua
- Biology and Health Laboratory, Department of Biology, Faculty of Science, Abdelmalek-Essaadi University, Tetouan, Morocco.
| | - Nasreddine El Omari
- Laboratory of Histology, Embryology, and Cytogenetic, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco.
| | - Douae Taha
- Laboratoire de Spectroscopie, Modélisation Moléculaire, Matériaux, Nanomatériaux, Eau et Environnement, CERNE2D, Faculté des Sciences, Université Mohammed V, Rabat, Morocco.
| | - Najoua Salhi
- Laboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco.
| | - Mohammad Ali Shariati
- Departement of Technology of Food Production, K.G. Razumoysky Moscow State University of Technologies and Management (the First Cossack University), 109004, Moscow, Russian Federation.
| | - Tarik Aanniz
- Environment and Health Team, Polydisciplinary Faculty of Safi, Cadi Ayyad University, Marrakech, Morocco.
| | - Taoufiq Benali
- Medical Biotechnology Laboratory (MedBiotech), Rabat Medical & Pharmacy School, Mohammed V University in Rabat, 6203, Rabat, Morocco.
| | - Gokhan Zengin
- Biochemistry and Physiology Laboratory, Department of Biology, Faculty of Science, Selcuk University, Campus, Konya, Turkey.
| | - Mohamed El-Shazly
- Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, 11566, Egypt; Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, 11835, Egypt.
| | - Imane Chamkhi
- Laboratory of Plant-Microbe Interactions, AgroBioSciences, Mohammed VI Polytechnic University, Ben Guerir, Morocco; Centre GEOPAC, Laboratoire de Geobiodiversite et Patrimoine Naturel Université Mohammed V de, Institut Scientifique Rabat, Morocco.
| | - Abdelhakim Bouyahya
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, And Genomic Center of Human Pathologies, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco.
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Therapeutic and Preventive Effects of Olea europaea Extract on Indomethacin-Induced Small Intestinal Injury Model in Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:6669813. [PMID: 33424990 PMCID: PMC7773470 DOI: 10.1155/2020/6669813] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 11/30/2020] [Accepted: 12/10/2020] [Indexed: 12/18/2022]
Abstract
Background Olea europaea (known as olive fruit) has anti-inflammatory and antioxidant activities and many potential health benefits including gastric inflammation reduction has been shown previously. This study aimed to investigate the preventive and therapeutic effects of O. europaea extract on the early histological changes in indomethacin-induced small intestinal injury model with the plasma D-lactate concentration being measured as a tool for determination of intestinal permeability. Methods In this experimental study, two separate protective and therapeutic protocols were designed. In both experiments, male Wistar rats were randomly divided into 4 groups and either pretreated with 0, 100, 200, or 400 mg/kg/day of O. europaea extract or received the treatment after administration of indomethacin. Their small intestines were examined to compare the histological changes. The intestinal injury severity was evaluated according to the presence of eosinophils, plasma cell infiltration, edema, congestion, and hyperplasia of the crypt using a histological scoring system. Also, measured were the presence of neutrophils, decreased villus length-to-crypt depth ratio, and destructed villus architecture. The plasma concentration of D-lactate was measured as well. Results The therapeutic use of O. europaea decreased the eosinophil, edema, congestion, and crypt hyperplasia scores compared to the control group. Although no significant difference was seen between groups of the preventive experiment in plasma cell infiltration score, villus length-to-crypt depth ratio, neutrophil infiltration, and percentage of destructed villus architecture, treatment with O. europaea caused a reduction in edema, eosinophil, congestion, and crypt hyperplasia score. In both experiments, no significant difference was seen between groups for villus length-to-crypt depth ratio, neutrophil infiltration, and percentage of destructed villus architecture. Plasma D-lactate concentration was decreased in all O. europaea-treated groups compared to the control group in the therapeutic and preventive experiments (p < 0.01, one-way ANOVA followed by the Dunnett test). Conclusion O. europaea extract can be used to decrease some side effects of indomethacin on intestinal tissue and enhances the gastrointestinal function. O. europaea extract could be considered as a potential herbal supplement in the treatment of intestinal morphological injuries.
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Matah Marte VM, Ateufack G, Mbiantcha M, Atsamo AD, Adjouzem CF, Djuichou Nguemnang SF, Tsafack EG, Yousseu Nana W, Madjo Kouam YK, Ngoufack Azanze E. Methanolic Extract of Distemonanthus benthamianus (Caesalpiniaceae) Stem Bark Suppresses Ethanol/Indomethacin-Induced Chronic Gastric Injury in Rats. Gastroenterol Res Pract 2020; 2020:8180323. [PMID: 33354210 PMCID: PMC7737456 DOI: 10.1155/2020/8180323] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 08/01/2020] [Accepted: 11/15/2020] [Indexed: 01/11/2023] Open
Abstract
Distemonanthus benthamianus (Caesalpiniaceae) is a plant from the Cameroon pharmacopoeia very widely used in the treatment of many pathologies among which are gastrointestinal disorders. The main purpose of this study was to assess the healing properties of gastric ulcer from the methanolic extract of Distemonanthus benthamianus and its mechanisms of action. The healing properties of gastric ulcers (chronic ulcer model induced by ethanol and indomethacin) were evaluated in vivo in adult male rats, while the mechanisms of action were evaluated in vitro by anti-inflammatory assay (protein denaturation, cyclooxygenase, and lipoxygenase assays) and immunomodulatory assay (ROS production (using technical chemiluminescence), cytokine (TNF-α, IL-1β, IL-6) production (using ELISA), proliferation of T cells (using liquid scintillation counter), and cytotoxicity (using MTT assay)). The methanolic extract of Distemonanthus benthamianus inhibited protein denaturation (75.63%) and the activities of cyclooxygenase (78.92%) and 5-lipoxygenase (81.54%). The extract also significantly (p < 0.001) inhibited intracellular and extracellular ROS production and T cell proliferation and reduced significantly (p < 0.01, p < 0.001) TNF-α, IL-1β, IL-6, and PGE2 production. At all doses (125, 250, and 500 mg/kg), the extract significantly reduces the ulceration index and the area of ulceration and significantly increases the mass of gastric mucus. In addition, the extract significantly decreases the level of MDA, significantly increases the activities of catalase and glutathione, and then improves the hematological parameters in sick animals. Histological micrographs show that in the presence of the extract, there is advanced reepithelialization with recovery of the ulcerated epithelium. Thus, the extract of Distemonanthus benthamianus has healing properties against gastric ulcers which are associated with its anti-inflammatory, immunomodulatory, and antioxidant effects.
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Affiliation(s)
- Vanessa Mba Matah Marte
- Laboratory of Animal Physiology and Phytopharmacology, Faculty of Science, University of Dschang, Cameroon
| | - Gilbert Ateufack
- Laboratory of Animal Physiology and Phytopharmacology, Faculty of Science, University of Dschang, Cameroon
| | - Marius Mbiantcha
- Laboratory of Animal Physiology and Phytopharmacology, Faculty of Science, University of Dschang, Cameroon
| | - Albert Donatien Atsamo
- Laboratory of Animal Physiology, Faculty of Science, University of Yaounde I, P.O. Box 812, Yaoundé, Cameroon
| | - Carine Flore Adjouzem
- Laboratory of Animal Physiology and Phytopharmacology, Faculty of Science, University of Dschang, Cameroon
| | | | - Eric Gonzal Tsafack
- Laboratory of Animal Physiology and Phytopharmacology, Faculty of Science, University of Dschang, Cameroon
| | - William Yousseu Nana
- Laboratory of Animal Physiology and Phytopharmacology, Faculty of Science, University of Dschang, Cameroon
| | - Yacine Karelle Madjo Kouam
- Laboratory of Animal Physiology and Phytopharmacology, Faculty of Science, University of Dschang, Cameroon
| | - Elvira Ngoufack Azanze
- Laboratory of Animal Physiology and Phytopharmacology, Faculty of Science, University of Dschang, Cameroon
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15
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Suleiman JB, Nna VU, Zakaria Z, Othman ZA, Eleazu CO, Abu Bakar AB, Ahmad A, Usman UZ, Abdul Rahman WFW, Mohamed M. Protective effects of bee bread on testicular oxidative stress, NF-κB-mediated inflammation, apoptosis and lactate transport decline in obese male rats. Biomed Pharmacother 2020; 131:110781. [PMID: 33152939 DOI: 10.1016/j.biopha.2020.110781] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 09/15/2020] [Accepted: 09/17/2020] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress, chronic inflammation and apoptosis are associated with obesity. Herein, we investigated the potential protective effect of bee bread, a natural bee product, on testicular oxidative stress, inflammation and apoptosis, as well as lactate transport in the testis of high-fat diet (HFD)-induced obese rats. Adult male Sprague-Dawley rats were either fed with normal chow (NC), HFD, HFD + bee bread (0.5 g/kg b.w./day) or HFD + orlistat (10 mg/kg b.w./day) for 12 weeks. Our results show significant decreases in the activities and mRNA expression of antioxidant genes (Nrf2, Sod, Cat and Gpx), with significant increase in pro-inflammatory (Nf-κb, Tnf-α, iNos, Il-1β) and pro-apoptotic (p53, Bax, Bax/Bcl2, Caspase-8, Caspase-9 and Caspase-3) genes in the testis of HFD group relative to the NC group. Furthermore, proliferating cell nuclear antigen (PCNA) was poorly expressed in the testis of the HFD group relative to the NC group. Similarly, the mRNA levels of glucose transporters (Glut1 and Glut3), monocarboxylate transporters (Mct2 and Mct4) and lactate dehydrogenase type C (Ldhc) decreased significantly, with decrease in lactate utilisation. Treatment with bee bread upregulated testicular antioxidant enzymes, downregulated inflammation and apoptosis, and increased PCNA immunoexpression, in addition to improving lactate transport. Taken together, our results suggest that bee bread is a promising natural product with the potential to improve male fertility.
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Affiliation(s)
- Joseph Bagi Suleiman
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia; Department of Science Laboratory Technology, Akanu Ibiam Federal Polytechnic, Unwana, Afikpo, Ebonyi State, Nigeria
| | - Victor Udo Nna
- Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, P.M.B., 1115, Calabar, Cross River State, Nigeria
| | - Zaida Zakaria
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Zaidatul Akmal Othman
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia; Unit of Physiology, Faculty of Medicine, Universiti Sultan Zainal Abidin, 20400, Kuala Terengganu, Terengganu, Malaysia
| | - Chinedum Ogbonnaya Eleazu
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia; Department of Chemistry/Biochemistry/Molecular Biology, Federal University Ndufu Alaike Ikwo, Abakiliki P.M.B. 10, Ebonyi State, Nigeria
| | - Ainul Bahiyah Abu Bakar
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Azlina Ahmad
- Basic Science and Oral Biology Unit, School of Dental Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Umar Zayyanu Usman
- Department of Physiology, College of Health Sciences, Usman Danfodiyo University, Sokoto, Nigeria
| | - Wan Faiziah Wan Abdul Rahman
- Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Mahaneem Mohamed
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia; Unit of Integrative Medicine, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia.
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16
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Zhou W, Zhang J, Toki S, Goleniewska K, Norlander AE, Newcomb DC, Wu P, Boyd KL, Kita H, Peebles RS. COX Inhibition Increases Alternaria-Induced Pulmonary Group 2 Innate Lymphoid Cell Responses and IL-33 Release in Mice. THE JOURNAL OF IMMUNOLOGY 2020; 205:1157-1166. [PMID: 32690653 DOI: 10.4049/jimmunol.1901544] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 06/22/2020] [Indexed: 01/08/2023]
Abstract
The cyclooxygenase (COX) metabolic pathway regulates immune responses and inflammation. The effect of the COX pathway on innate pulmonary inflammation induced by protease-containing fungal allergens, such as Alternaria alternata, is not fully defined. In this study, we tested the hypothesis that COX inhibition augments Alternaria-induced pulmonary group 2 innate lymphoid cell (ILC2) responses and IL-33 release. Mice were treated with the COX inhibitors indomethacin, flurbiprofen, or vehicle and challenged intranasally with Alternaria extract for four consecutive days to induce innate lung inflammation. We found that indomethacin and flurbiprofen significantly increased the numbers of ILC2 and IL-5 and IL-13 expression by ILC2 in the lung. Indomethacin also increased ILC2 proliferation, the percentages of eosinophils, and mucus production in the lung. Both indomethacin and flurbiprofen augmented the release of IL-33 in bronchoalveolar lavage fluid after Alternaria challenge, suggesting that more IL-33 was available for ILC2 activation and that a COX product(s) inhibited IL-33 release. This is supported by the in vitro finding that the COX product PGE2 and the PGI2 analogs cicaprost decreased Alternaria extract-induced IL-33 release by human bronchial epithelial cells. Although contrasting effects of PGD2, PGE2, and PGI2 on ILC2 responses have been previously reported, the overall effect of the COX pathway on ILC2 function is inhibitory in Alternaria-induced innate airway inflammation.
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Affiliation(s)
- Weisong Zhou
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Nashville, TN 37232;
| | - Jian Zhang
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Nashville, TN 37232
| | - Shinji Toki
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Nashville, TN 37232
| | - Kasia Goleniewska
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Nashville, TN 37232
| | - Allison E Norlander
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Nashville, TN 37232
| | - Dawn C Newcomb
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Nashville, TN 37232
| | - Pingsheng Wu
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Nashville, TN 37232
| | - Kelli L Boyd
- Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232; and
| | - Hirohito Kita
- Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905
| | - R Stokes Peebles
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Nashville, TN 37232.,Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232; and
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17
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Şen LS, Özdemir Kumral ZN, Memi G, Ercan F, Yeğen BC, Yeğen C. The gastroprotective effect of obestatin on indomethacin-induced acute ulcer is mediated by a vagovagal mechanism. Physiol Int 2020; 107:243-255. [PMID: 32692714 DOI: 10.1556/2060.2020.00025] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 02/17/2020] [Indexed: 12/12/2022]
Abstract
In order to investigate the role of the vagus nerve in the possible gastroprotective effect of obestatin on the indomethacin-induced acute oxidative gastric injury, Sprague-Dawley rats of both sexes were injected subcutaneously with indomethacin (25 mg/kg, 5% NaHCO3) followed by obestatin (10, 30 or 100 μg/kg). In other sets of rats, surgical vagotomy (Vx) or selective degeneration of vagal afferent fibers by perivagal capsaicin was performed before the injections of indomethacin or indomethacin + obestatin (30 μg/kg). Gastric serosal blood flow was measured, and 4 h after ulcer induction gastric tissue samples were taken for histological and biochemical assays. Obestatin reduced the severity of indomethacin-induced acute ulcer via the reversal of reactive hyperemia, by inhibiting ulcer-induced neutrophil infiltration and lipid peroxidation along with the replenishment of glutathione (GSH) stores, whereas Vx abolished the inhibitory effect of obestatin on blood flow and lipid peroxidation, and worsened the severity of ulcer. On the other hand, serosal blood flow was even amplified by the selective denervation of the capsaicin-sensitive vagal afferent fibers, but obestatin-induced reduction in ulcer severity was not altered. In conclusion, the gastroprotective effect of obestatin on indomethacin-induced ulcer appears to involve the activation of the vagovagal pathway.
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Affiliation(s)
- Leyla Semiha Şen
- 1Department of Physiology, Marmara University School of Medicine, İstanbul, Turkey.,3Department of General Surgery, Marmara University School of Medicine, İstanbul, Turkey
| | | | - Gülsün Memi
- 1Department of Physiology, Marmara University School of Medicine, İstanbul, Turkey
| | - Feriha Ercan
- 2Department of Histology & Embryology, Marmara University School of Medicine, İstanbul, Turkey
| | - Berrak C Yeğen
- 1Department of Physiology, Marmara University School of Medicine, İstanbul, Turkey
| | - Cumhur Yeğen
- 3Department of General Surgery, Marmara University School of Medicine, İstanbul, Turkey
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18
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Cao L, Li X, Xu R, Yao K, Yang W, Zhu H, Wang G, Zhang J. DUOX2, a common modulator in preventive effects of monoamine-based antidepressants on water immersion restraint stress- and indomethacin- induced gastric mucosal damage. Eur J Pharmacol 2020; 876:173058. [PMID: 32131022 DOI: 10.1016/j.ejphar.2020.173058] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 02/28/2020] [Accepted: 02/28/2020] [Indexed: 01/06/2023]
Abstract
Multiple kinds of monoamine-based antidepressants have been shown prophylactic effects in experimentally induced gastric ulcer. The loss of redox homeostasis plays a principle role in the development of peptic mucosal damage. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are one of the most important sources of reactive oxygen species within the gastrointestinal tract. It is unclear whether there are some common NADPH oxidases modulated by monoamine-based antidepressants in different gastric mucosal damage models. We explored the effects of selective serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine on the reactive oxygen species production and antioxidant capacity in the gastric mucosa of water immersion restraint (WIRS) or indomethacin treated rats, and examined the role of NADPH oxidases in the protective effects. Pretreated duloxetine prevented the increase of gastric mucosal NADPH oxidase activity and NADPH oxidase inhibitor apocynin dose-dependently protected gastric mucosa from damage by the two factors. Furthermore, dual oxidase 2 (DUOX2) and NADPH oxidase4 (NOX4) are involved in the protective effects of duloxetine in both models. We then examined NADPH oxidases expression modulated by the other monoamine-based antidepressants including selective serotonin reuptake inhibitor (SSRIs) fluoxetine, tricyclic agent (TCAs) amitriptyline and monoamine oxidase inhibitor (MAOs) moclobemide in the two models, and all the three antidepressants reduced the DUOX2 expression in the gastric mucosa. So DUOX2 was a common modulator in the preventive effects of all the monoamine-based antidepressants on WIRS- and indomethacin-induced gastric lesion. Our work provided a peripheral joint molecular target for monoamine modulatory antidepressants, which may be helpful to reveal the mechanisms of this kind of drugs more than monoamine regulation.
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Affiliation(s)
- Linyu Cao
- Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, China
| | - Xulin Li
- Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, China
| | - Ruiming Xu
- Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, China
| | - Kaiyun Yao
- Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, China
| | - Wanqi Yang
- Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, China
| | - Hongliang Zhu
- Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, China
| | - Guibin Wang
- Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, China.
| | - Jianjun Zhang
- Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, China.
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The Use of Pistacia Lentiscus Chia Resin Versus Omeprazole in Protecting Male Rats Peptic Mucosa Against Cold Restraint Stress. ACTA ACUST UNITED AC 2020; 6:100-110. [PMID: 32426516 PMCID: PMC7216028 DOI: 10.2478/jccm-2020-0018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 04/14/2020] [Indexed: 12/11/2022]
Abstract
Introduction Peptic mucosal damage induced by acute stress is a serious cause of morbidity and mortality in critically ill patients. The study aimed to investigate the protective, antioxidant and anti-inflammatory effects of pretreatment with Chios mastic gum (CMG), a traditionally consumed herbal resin naturally deriving from the trunk of Pistacia Lentiscus var. Chia compared to Omeprazole, a standard medication used in the prevention and treatment of gastritis, against the effects of cold restraint stress (CRS) in rat gastric and colonic mucosa. Methods Twenty-one male Wistar rats were randomly assigned to three groups: Control (C), Omeprazole (O), and CMG (M), according to the pre-treatment regime, and were subjected to CRS at 40C for 3 hours. The gastric and colonic mucosal lesions were histologically assessed. ELISA measured blood concentrations of TNF-α, IL-1β, peroxidase, superoxide dismutase (SOD) and total antioxidant capacity (TEAC). Results In both groups, O and M, gastric mucosal hyperemia, haemorrhagic infiltration and mucosal oedema, as well as colonic mucosal hyperaemia and haemorrhagic infiltration were significantly reduced compared to the controls (p<0.05). No significant differences were observed between Groups O and M. TNF-α levels were significantly lower in group M compared to Group O (p=0.013). IL-1β levels were significantly depressed in groups M and O compared to control (p≤ 0.001). The activity of both peroxidase and SOD enzymes decreased in group M compared to group O (p= 0.043 and p=0.047 respectively) and the control (p=0.018 and p< 0.001 respectively). Conclusions The natural Chios mastic gum is a promising nutritional supplement with protective properties to the peptic mucosa against CRS, exerting anti-inflammatory and antioxidant effects.
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Raychaudhuri S, Ghosh S, Roy A, Swarnakar S. Protective Role of Black Tea Flavonoids Against Ethanol-Induced Gastropathy via Matrix Metalloproteinase Pathway. Indian J Clin Biochem 2019; 34:379-394. [PMID: 31686725 DOI: 10.1007/s12291-018-0762-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Accepted: 05/29/2018] [Indexed: 02/06/2023]
Abstract
Abstract Tea polyphenols are known to prevent various ailments like cancer, atherosclerosis, hypertension and diabetes. Our study aimed at to decipher the gastroprotective effect of aqueous black tea extract (BTE) against ethanol-induced gastric damage and the role of BTE in modulating MMP-9 activity and expression, both in vivo and in vitro. The protective role of BTE was assessed in Sprague-Dawley rats after inducing damage with 70% ethanol. Human gastric adenocarcinoma cells (AGS) were treated with ethanol in ex vivo experiment. MMP-9 activity and expression were investigated through gelatin zymography and western blotting. Reactive oxygen species (ROS) generation was also studied by fluorescence spectroscopy and confocal microscopy, with or without treatment of BTE both in vivo and in vitro experiments. In addition, the effect of citric acid treated BTE (cBTE), which mimics lemon tea, was examined on ethanol-induced gastropathy. BTE exhibited antiulcer activity through reduction of glutathione depletion, lipid peroxidation, protein oxidation, ROS production and inflammatory cell infiltration in rat gastric tissues. In addition, BTE significantly inhibited synthesis and secretion of proMMP-9 both in vivo and in vitro. The mitochondrial enzymes succinate dehydrogenase and NADH oxidase in rat gastric tissues were downregulated by BTE while protecting gastric ulcer. Citric acid addition to BTE was observer to enrich the lead compound, catechin. Interestingly, cBTE showed higher anti-ulcer activity than the untreated one. BTE shows protective role against ethanol-induced gastric ulcer in rats through scavenging ROS and downregulating proMMP-9 activity. While cBTE shows better protection due to enrichment of catechin and removal of tannins in tea extract leading to enhanced inhibitory role on proMMP-9 activity and ROS production. Graphical Abstract
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Affiliation(s)
- Susri Raychaudhuri
- 1Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, 700 032 India
| | - Satyabrata Ghosh
- 2Department of Food Technology and Biochemical Engineering, Jadavpur University, Kolkata, 700 032 India
| | - Anirban Roy
- 1Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, 700 032 India
| | - Snehasikta Swarnakar
- 1Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, 700 032 India
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Yasukawa K, Shigemi R, Kanbe T, Mutsumoto Y, Oda F, Ichikawa K, Yamada KI, Tun X, Utsumi H. In Vivo Imaging of the Intra- and Extracellular Redox Status in Rat Stomach with Indomethacin-Induced Gastric Ulcers Using Overhauser-Enhanced Magnetic Resonance Imaging. Antioxid Redox Signal 2019; 30:1147-1161. [PMID: 29631421 DOI: 10.1089/ars.2017.7336] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
AIMS Repeated use of nonsteroidal anti-inflammatory drugs can induce changes in the redox status, including production of reactive oxygen species (ROS), but the specific details of these changes remain unknown. Overhauser-enhanced magnetic resonance imaging (OMRI) has been used in vivo to monitor the redox status in several diseases and map tissue oxygen concentrations. We monitored the intra- and extracellular redox status in the stomach of rats with indomethacin-induced gastric ulcers using OMRI and investigated the relationship with gastric mucosal damage. RESULTS One hour after oral administration of indomethacin (30 mg/kg), OMRI measurements in the stomach were made following nitroxyl probe administration. OMRI with the membrane-permeable nitroxyl probe, 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl (TEMPOL), demonstrated a redox change toward oxidation, which was reversed by a membrane-permeable antioxidant. Conversely, imaging with the impermeable probe, 4-trimethylammonium-2,2,6,6-tetramethyl-piperidine-1-oxyl (CAT-1), demonstrated little redox change. Redox imbalance imaging of a live rat stomach with indomethacin-induced gastric ulcers was produced by dual imaging of 15N-labeled TEMPOL and 14N-labeled CAT-1, in addition to imaging with another membrane-permeable 15N-labeled probe, 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL), and 14N-labeled CAT-1. Pretreatment with MC-PROXYL suppressed gastric mucosal damage, whereas pretreatment with CAT-1 did not suppress ulcer formation. INNOVATION OMRI combined with a dual probe is a less invasive imaging technique for evaluation of intracellular ROS production contributing to the formation of gastric ulcers in the stomach of indomethacin-treated rats, which cannot be done with other methods. CONCLUSION This method may be a very powerful tool for characterizing the pathogenesis of various diseases and may have medical applications.
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Affiliation(s)
- Keiji Yasukawa
- 1 Laboratory of Advanced Pharmacology, Daiichi University of Pharmacy, Fukuoka, Japan.,2 Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.,3 Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan
| | - Ryota Shigemi
- 2 Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomomi Kanbe
- 2 Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
| | - Yusaku Mutsumoto
- 2 Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
| | - Fumiko Oda
- 2 Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
| | - Kazuhiro Ichikawa
- 3 Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan
| | - Ken-Ichi Yamada
- 2 Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
| | - Xin Tun
- 4 Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
| | - Hideo Utsumi
- 5 School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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de Souza MC, Vieira AJ, Beserra FP, Pellizzon CH, Nóbrega RH, Rozza AL. Gastroprotective effect of limonene in rats: Influence on oxidative stress, inflammation and gene expression. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2019; 53:37-42. [PMID: 30668410 DOI: 10.1016/j.phymed.2018.09.027] [Citation(s) in RCA: 93] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Revised: 07/31/2018] [Accepted: 09/03/2018] [Indexed: 06/09/2023]
Abstract
BACKGROUND In an increasing search for natural products that may heal the ulcers and avoid its recurrence, limonene appears as a promising candidate. HYPOTHESIS/PURPOSE The present study aimed to investigate the protective effect of limonene in ethanol-induced gastric ulcers, in addition, to investigate the involvement of antioxidant and anti-inflammatory activities, besides the modulation of gene expression. STUDY DESIGN Male Wistar rats were orally treated with vehicle (8% tween 80), carbenoxolone (100 mg/kg) or limonene (25, 50 or 100 mg/kg) and then orally received ethanol to induce gastric ulcers formation. METHODS The activity of myeloperoxidase (MPO) was measured. Levels of glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase (SOD) were measured. We investigated the anti-inflammatory effect of limonene measuring the levels of pro-inflammatory cytokines tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1β (IL-1β) and anti-inflammatory cytokine interleukin-10 (IL-10) by ELISA. Additionally, we investigate through real-time PCR (qPCR) the gene expression of nuclear factor-kappa B (Nf-κb), Gpx, Il-1β, Mpo, and Il-10. RESULTS Our results showed that limonene 50 mg/kg was the lowest effective dose, offering 93% of reduction in gastric ulcer area compared with the vehicle. There was an increase in mucus production and higher preservation of gastric mucosa integrity after treatment with limonene.There was a reduction in the MPO activity, a biomarker of neutrophils infiltration, and an increase in GPx activity, suggesting an antioxidant effect. Limonene displayed anti-inflammatory activity through decreasing the levels of TNF-a, IL-6, and IL-1β and increasing the level of IL-10. Limonene could down-regulate the expression of Nf-κb, Il-1β, and Mpo and up-regulate the expression of Gpx. CONCLUSION Our results demonstrate that oral treatment with limonene exerts gastroprotection through local mucosal defense mechanisms, such as increasing the mucus production, modulation of the oxidative stress and inflammatory response and inhibition of Nf-κb expression.
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Affiliation(s)
- Matheus Chiaradia de Souza
- Department of Morphology, São Paulo State University (UNESP), Institute of Biosciences, Botucatu, Brazil
| | - Ana Júlia Vieira
- Department of Morphology, São Paulo State University (UNESP), Institute of Biosciences, Botucatu, Brazil
| | - Fernando Pereira Beserra
- Department of Morphology, São Paulo State University (UNESP), Institute of Biosciences, Botucatu, Brazil
| | - Cláudia Helena Pellizzon
- Department of Morphology, São Paulo State University (UNESP), Institute of Biosciences, Botucatu, Brazil
| | - Rafael Henrique Nóbrega
- Department of Morphology, São Paulo State University (UNESP), Institute of Biosciences, Botucatu, Brazil
| | - Ariane Leite Rozza
- Department of Morphology, São Paulo State University (UNESP), Institute of Biosciences, Botucatu, Brazil.
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Antioxidant effects of Allium cepa and cinnamon on biochemical parameters and ultrastructure of ovarian tissue in extremely low frequency electromagnetic field exposed rats. ACTA ACUST UNITED AC 2019. [DOI: 10.1007/s00580-018-2884-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Jiao Y, Kuang H, Hu J, Chen Q. Structural characterization and anti-hypoxia activities of polysaccharides from the sporocarp, fermentation broth and cultured mycelium of Agaricus bitorquis (Quél.) Sacc. Chaidam in mice. J Funct Foods 2018. [DOI: 10.1016/j.jff.2018.10.017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
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Khayyat SA, Roselin LS. Recent progress in photochemical reaction on main components of some essential oils. JOURNAL OF SAUDI CHEMICAL SOCIETY 2018. [DOI: 10.1016/j.jscs.2018.01.008] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Zhao H, Zhang J, Liu X, Yang Q, Dong Y, Jia L. The antioxidant activities of alkalic-extractable polysaccharides from Coprinus comatus on alcohol-induced liver injury in mice. Sci Rep 2018; 8:11695. [PMID: 30076364 PMCID: PMC6076309 DOI: 10.1038/s41598-018-30104-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Accepted: 07/24/2018] [Indexed: 01/08/2023] Open
Abstract
The aim of this work was to provide a preliminary characterization of alkalic-extractable polysaccharides (ALPS) from Coprinus comatus, to explore its in vivo antioxidant activities and protective effects on alcohol-induced liver injury. ALPS showed strong antioxidant and anti-inflammatory abilities and markedly low serum enzyme activities, hepatic and serum lipid levels, as well as low hepatic lipid peroxidation levels; moreover, ALPS improved the alcohol metabolism system. These results were also confirmed by an analysis of histopathological section observations. ALPS, in both α- and β-configurations, as analysed by fourier-transform infrared (FT-IR) and nuclear magnetic resonance (NMR), was mainly composed of rhamnose (Rha), fucose (Fuc), ribose (Rib), xylose (Xyl), mannose (Man), galactose (Gal) and glucose (Glu) with mass percentages of 0.52%, 1.02%, 0.80%, 0.92%, 3.05%, 2.96% and 90.73%, respectively. These results may offer support for the use of ALPS as a functional food or natural drug source that can prevent and treat alcohol-induced liver injury.
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Affiliation(s)
- Huajie Zhao
- College of Life Science, Shandong Agricultural University, Taian, 271018, P.R. China
| | - Jianjun Zhang
- College of Life Science, Shandong Agricultural University, Taian, 271018, P.R. China
| | - Xinchao Liu
- College of Life Science, Shandong Agricultural University, Taian, 271018, P.R. China
| | - Qihang Yang
- College of Life Science, Shandong Agricultural University, Taian, 271018, P.R. China
| | - Yuhan Dong
- College of Life Science, Shandong Agricultural University, Taian, 271018, P.R. China
| | - Le Jia
- College of Life Science, Shandong Agricultural University, Taian, 271018, P.R. China.
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Testosterone alleviates mitochondrial ROS accumulation and mitochondria-mediated apoptosis in the gastric mucosa of orchiectomized rats. Arch Biochem Biophys 2018; 649:53-59. [PMID: 29733810 DOI: 10.1016/j.abb.2018.05.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 04/28/2018] [Accepted: 05/03/2018] [Indexed: 01/25/2023]
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Magierowska K, Brzozowski T, Magierowski M. Emerging role of carbon monoxide in regulation of cellular pathways and in the maintenance of gastric mucosal integrity. Pharmacol Res 2018; 129:56-64. [PMID: 29360501 DOI: 10.1016/j.phrs.2018.01.008] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Revised: 01/12/2018] [Accepted: 01/18/2018] [Indexed: 12/14/2022]
Abstract
Heme oxygenase (HO) catalyzes the degradation of toxic free heme to the equimolar amounts of biliverdin, Fe2+ and concurrently releases of carbon monoxide (CO). CO is nowadays increasingly recognized as an important signaling molecule throughout the body that is involved in many physiological processes and shows multidirectional biological activity. Recent evidence indicates that CO exhibits the anti-inflammatory, anti-proliferative, anti-apoptotic, anti-aggregatory and vasodilatory properties. The cellular mechanisms underlying the activity of CO involve stimulation of cGMP-dependent signaling pathway and large conductance calcium activated K+ channels, the activation of mitogen-activated protein kinases and the nuclear factor k-light chain-enhancer of activated B cells transcription factor pathway. Stimulation of endogenous CO production by HO inducers or the inhalation of CO or the delivery of this gaseous molecule by novel pharmaceutical agents have been found in experimental animal models to be promising in the future therapy of various diseases. CO appears to act as a significant component of the complex mechanism of gastrointestinal (GI) mucosal defense. This gaseous molecule plays an important role in diabetic gastroparesis, prevention of the upper GI mucosal damage, post-operative ileus and the healing of ulcerative colitis. This review focuses on the better understanding mechanisms through which CO contributes to the mechanism of protection, resistance to injury and ulcer healing. It is becoming apparent that the pleiotropic effect of this molecule may increase clinical applicability of CO donors and their implementation in many pharmacological research areas, pharmaceutical industry and health-care system.
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Affiliation(s)
- Katarzyna Magierowska
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland
| | - Tomasz Brzozowski
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland
| | - Marcin Magierowski
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland.
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Minaiyan M, Sajjadi SE, Amini K. Antiulcer effects of Zataria multiflora Boiss. on indomethacin-induced gastric ulcer in rats. AVICENNA JOURNAL OF PHYTOMEDICINE 2018; 8:408-415. [PMID: 30345228 PMCID: PMC6190242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE Zataria multiflora has been reported to have several medicinal properties including antioxidant, antibacterial, antispasmodic, and expectorant activities. This study aimed to investigate the effect of Z. multiflora hydro-alcoholic extract (ZMHE) on peptic ulcer caused by indomethacin in rats. MATERIALS AND METHODS ZMHE was prepared by maceration, condensed by rotary evaporator and dried by a freeze-drier. In this study, 72 male Wistar rats were randomly divided into 12 groups, six in each including: normal rats, control rats, ranitidine-treated, and animals that were treated with ZMHE (100, 200, 400 mg/kg). Parenteral and oral treatments were done 1 and 2 hours, respectively before gastric ulcer induction by indomethacin (25 mg/kg, i.p.). After 6 hours, animals were sacrificed, two sides of the stomach were ligated and gastric contents and tissues were investigated in terms of pH and biochemical and histologic parameters, respectively. RESULTS ZMHE (at all doses) considerably decreased the ulcer area and ulcer severity in comparison to control group after oral and parenteral administration. Oral administration of this extract increased the pH of stomach contents while diminished pepsin activity in a dose-dependent manner. Following parenteral treatment, a significant difference in pH of stomach content was observed only by ZMHE 400mg/kg in comparison to control group. The myeloperoxidase (MPO) enzyme activity decreased in groups that received the extract via both oral and parenteral routes. CONCLUSION It might be concluded that ZMHE could protect against experimental gastric ulcer induced by indomethacin and this action is probably mediated via reducing acid secretion and pepsin activity besides enhancing tissue antioxidant capacity.
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Affiliation(s)
- Mohsen Minaiyan
- Department of Pharmacology and Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran,Corresponding Author:Tel: +983137927088, Fax: +983136680011,
| | - Sayed-Ebrahim Sajjadi
- Department of Pharmacognosy, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Kamran Amini
- Schools of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
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Kouitcheu Mabeku LB, Nanfack Nana B, Eyoum Bille B, Tchuenteu Tchuenguem R, Nguepi E. Anti-Helicobacter pylori and antiulcerogenic activity of Aframomum pruinosum seeds on indomethacin-induced gastric ulcer in rats. PHARMACEUTICAL BIOLOGY 2017; 55:929-936. [PMID: 28164737 PMCID: PMC6130624 DOI: 10.1080/13880209.2017.1285326] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2016] [Revised: 12/04/2016] [Accepted: 01/17/2017] [Indexed: 05/03/2023]
Abstract
CONTEXT Peptic ulcer is one of the most common diseases affecting mankind. Although there are many products used for its treatment, most of these products produce severe adverse reactions requiring the search for novel compounds. Some Afromomum species are used traditionally to cure acute gastritis. OBJECTIVE To evaluate the antiulcer activity of the methanol extract of Aframomum pruinosum Gagnepain (Zingiberaceae) seeds against two major etiologic agents of peptic ulcer disease; Helicobacter pylori and non-steroidal anti-inflammatory drugs. MATERIALS AND METHODS The anti-Helicobacter activity of A. pruinosum was evaluated using the broth microdilution method. After oral administration of indomethacin (5 mg/kg) for 5 consecutive days, gastric ulcerated animals were divided into control group and five other groups: three groups that recieved respectively 125, 250 and 500 mg/kg of plant extract, the fourth group received Maalox (50 mg/kg) and the fifth group, Misoprostol (100 μg/kg), respectively, for 5 days. Ulcer areas, gastric mucus content and nitric oxide gastric levels of animals were assessed 24 h after this treatment. RESULTS A. pruinosum extract shows a moderate anti-Helicobacter activity with an MIC value of 128 μg/mL. A. pruinosum extract, like Misoprostol and Maalox, markedly reduces the % of ulcerated area from 8.15 ± 0.33 to 1.71 ± 0.44% (500 mg/kg). It also increased significantly mucus and NO gastric production with respective values of 4.44 ± 1.35 and 965.81 ± 106.74 μmol/g (500 mg/kg). DISCUSSION AND CONCLUSION These findings suggest that A. pruinosum methanol extract possesses antiulcer properties as ascertained by the comparative decreases in ulcer areas, increase of mucus and NO gastric production.
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Affiliation(s)
- Laure Brigitte Kouitcheu Mabeku
- Microbiology and Pharmacology Laboratory, Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon
| | - Blandine Nanfack Nana
- Microbiology and Pharmacology Laboratory, Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon
| | - Bertrand Eyoum Bille
- Microbiology and Pharmacology Laboratory, Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon
| | - Roland Tchuenteu Tchuenguem
- Microbiology and Pharmacology Laboratory, Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon
| | - Eveline Nguepi
- Gastroenterology Department, Laquintinie Hospital of Douala, Douala, Cameroon
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Zhao X, Cheng Q, Qian Y, Yi R, Gu L, Wang S, Song JL. Insect tea attenuates hydrochloric acid and ethanol-induced mice acute gastric injury. Exp Ther Med 2017; 14:5135-5142. [PMID: 29201228 PMCID: PMC5704295 DOI: 10.3892/etm.2017.5181] [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: 10/10/2016] [Accepted: 06/22/2017] [Indexed: 02/07/2023] Open
Abstract
The aim of the present study was to investigate the protective effect of insect tea on HCl/ethanol-induced gastric ulcers in ICR mice. The serum levels of vasoactive intestinal peptide, substance P, somatostatin, motilin and endothelin-1 in mice were assessed using commercial kits and gastric tissues of superoxide dismutase (SOD, nitric oxide (NO) and malondialdehyde (MDA) were determined using western blot analysis Insect tea significantly reduced HCl/ethanol-induced gastric juice secretion and increased the pH of gastric juice (P<0.05). Insect tea treatment signfiicantly increased vasoactive intestinal peptide and somatostatin, and significantly decreased motilin, substance P and endothelin levels in the serum (P<0.05). Treatment with insect tea was demonstrated to significantly increase levels of gastric SOD and NO and to reduce levels of MDA in the gastric ulcer mouse model (P<0.05). The gastric expression of inhibitor of nuclear factor-κB (NF-κB), epidermal growth factor (EGF), EGF receptor, neuronal nitric oxide synthase (nNOS), endothelial NOS, Mn-SOD, Cu/Zn-SOD and catalase was significantly increased in mice treated with inset tea compared with untreated model mice (P<0.05). Levels of NF-κB, and inducible NOS were demonstrated to be decreased in mice treated with insect tea compared with untreated model mice (P<0.05). The results of the present study suggest that insect tea has a protective effect against HCl/ethanol-induced gastric ulcers in ICR mice. This effect may be achieved via modulating serum neuropeptide levels, reducing gastric juice secretion, and modulating the inflammation- and antioxidant-associated protein expressions in gastric tissue.
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Affiliation(s)
- Xin Zhao
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing 400067, P.R. China
- Chongqing Engineering Research Center of Functional Food, Chongqing University of Education, Chongqing 400067, P.R. China
- Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing 400067, P.R. China
- Department of Food Quality and Safety, Chongqing University of Education, Chongqing 400067, P.R. China
| | - Qiang Cheng
- Department of Nutrition and Food Hygiene, School of Public Health, Guilin Medical University, Guilin, Guangxi 541004, P.R. China
- Institute of Preventive Medicine, Guilin Medical University, Guilin, Guangxi 541004, P.R. China
| | - Yu Qian
- Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing 400067, P.R. China
- Department of Food Quality and Safety, Chongqing University of Education, Chongqing 400067, P.R. China
- Department of Nutrition and Food Hygiene, School of Public Health, Guilin Medical University, Guilin, Guangxi 541004, P.R. China
- Institute of Preventive Medicine, Guilin Medical University, Guilin, Guangxi 541004, P.R. China
| | - Ruokun Yi
- Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing 400067, P.R. China
- Department of Food Quality and Safety, Chongqing University of Education, Chongqing 400067, P.R. China
- Department of Nutrition and Food Hygiene, School of Public Health, Guilin Medical University, Guilin, Guangxi 541004, P.R. China
- Institute of Preventive Medicine, Guilin Medical University, Guilin, Guangxi 541004, P.R. China
| | - Lianjie Gu
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing 400067, P.R. China
| | - Shanshan Wang
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing 400067, P.R. China
| | - Jia-Le Song
- Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing 400067, P.R. China
- Department of Nutrition and Food Hygiene, School of Public Health, Guilin Medical University, Guilin, Guangxi 541004, P.R. China
- Institute of Preventive Medicine, Guilin Medical University, Guilin, Guangxi 541004, P.R. China
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32
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Purification, in vitro antioxidant and in vivo anti-aging activities of exopolysaccharides by Agrocybe cylindracea. Int J Biol Macromol 2017; 102:351-357. [DOI: 10.1016/j.ijbiomac.2017.04.039] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Revised: 03/03/2017] [Accepted: 04/10/2017] [Indexed: 01/22/2023]
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Etani R, Kataoka T, Kanzaki N, Sakoda A, Tanaka H, Ishimori Y, Mitsunobu F, Taguchi T, Yamaoka K. Protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice. JOURNAL OF RADIATION RESEARCH 2017; 58:614-625. [PMID: 28498931 PMCID: PMC5737809 DOI: 10.1093/jrr/rrx021] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Revised: 01/26/2017] [Accepted: 03/31/2017] [Indexed: 05/30/2023]
Abstract
Radon therapy using radon (222Rn) gas is classified into two types of treatment: inhalation of radon gas and drinking water containing radon. Although short- or long-term intake of spa water is effective in increasing gastric mucosal blood flow, and spa water therapy is useful for treating chronic gastritis and gastric ulcer, the underlying mechanisms for and precise effects of radon protection against mucosal injury are unclear. In the present study, we examined the protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice. Mice inhaled radon at a concentration of 2000 Bq/m3 for 24 h or were provided with hot spring water for 2 weeks. The activity density of 222Rn ranged from 663 Bq/l (start point of supplying) to 100 Bq/l (end point of supplying). Mice were then orally administered ethanol at three concentrations. The ulcer index (UI), an indicator of mucosal injury, increased in response to the administration of ethanol; however, treatment with either radon inhalation or hot spring water inhibited the elevation in the UI due to ethanol. Although no significant differences in antioxidative enzymes were observed between the radon-treated groups and the non-treated control groups, lipid peroxide levels were significantly lower in the stomachs of mice pre-treated with radon or hot spring water. These results suggest that hot spring water drinking and radon inhalation inhibit ethanol-induced gastric mucosal injury.
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Affiliation(s)
- Reo Etani
- Graduate School of Health Sciences, Okayama University, 5-1 Shikata-cho, 2-chome, Kita-ku, Okayama 700-8558, Japan
| | - Takahiro Kataoka
- Graduate School of Health Sciences, Okayama University, 5-1 Shikata-cho, 2-chome, Kita-ku, Okayama 700-8558, Japan
| | - Norie Kanzaki
- Graduate School of Health Sciences, Okayama University, 5-1 Shikata-cho, 2-chome, Kita-ku, Okayama 700-8558, Japan
| | - Akihiro Sakoda
- Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency 1550 Kamisaibara, Kagamino-cho, Tomata-gun, Okayama 708-0698, Japan
| | - Hiroshi Tanaka
- Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency 1550 Kamisaibara, Kagamino-cho, Tomata-gun, Okayama 708-0698, Japan
| | - Yuu Ishimori
- Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency 1550 Kamisaibara, Kagamino-cho, Tomata-gun, Okayama 708-0698, Japan
| | - Fumihiro Mitsunobu
- Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 5-1 Shikata-cho, 2-chome, Kita-ku, Okayama 700-8558, Japan
| | - Takehito Taguchi
- Graduate School of Health Sciences, Okayama University, 5-1 Shikata-cho, 2-chome, Kita-ku, Okayama 700-8558, Japan
| | - Kiyonori Yamaoka
- Graduate School of Health Sciences, Okayama University, 5-1 Shikata-cho, 2-chome, Kita-ku, Okayama 700-8558, Japan
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34
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Odukanmi OA, Salami AT, Ashaolu OP, Adegoke AG, Olaleye SB. Kolaviron attenuates ischemia/reperfusion injury in the stomach of rats. Appl Physiol Nutr Metab 2017; 43:30-37. [PMID: 28841395 DOI: 10.1139/apnm-2017-0138] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Kolaviron (KV), an active complex of at least 3 compounds in Garcinia kola seed, which is known for its antioxidant and anti-inflammatory activity, was investigated for its gastro-protective effect in the stomach of rats subjected to ischemia/reperfusion-induced gastric ulceration. Male adult Wistar rats (180-210 g) were randomized into 6 groups (n = 15) as follows: (i) control, (ii) ulcerated untreated (UU), (iii) KV alone (KVA), (iv) KV + ulcer (KVU), (v) ulcer + KV (UKV), and (vi) ulcer + omeprazole (20 mg/kg). Ulcer was induced through ischemia/reperfusion method after 2 weeks of daily oral KV (100 mg/kg). Rats were weighed daily, and gastric acid secretion, ulcer scores, hematological, biochemical, and histological variables were assessed 1 h after induction at 3 and 7 days post-ulceration. Body weight decreased in KVA (179.1 ± 1.6 g), and KVU (170.1 ± 2.2 g) compared with UU (199.0 ± 1.4 g). Gastric acid secretion decreased significantly in KVU after 1 h and 3 days post-ulceration (0.27 ± 0.03 mEq/L; 0.49 ± 0.02 mEq/L) compared with UU (0.60 ± 0.06 mEq/L; 0.85 ± 0.29 mEq/L), respectively. There was significant reduction in neutrophil/lymphocyte ratio of KVA (0.29 ± 0.06) and KVU (0.35 ± 0.02) compared with UU (0.54 ± 0.04). Malondialdehyde level decreased significantly with concomitant increase in anti-oxidative activities and nitric oxide level in the KV treated groups (KVA, KVU, UKV) compared with UU. In conclusion, treatment with KV protects the stomach by reducing gastric acid secretion, promoting antioxidant activity and suppressing action of reactive oxygen species.
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Affiliation(s)
- Olugbenga Adeola Odukanmi
- Laboratory for Gastrointestinal Secretions and Inflammation Research, Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria.,Laboratory for Gastrointestinal Secretions and Inflammation Research, Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Adeola Temitope Salami
- Laboratory for Gastrointestinal Secretions and Inflammation Research, Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria.,Laboratory for Gastrointestinal Secretions and Inflammation Research, Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Onaara Peter Ashaolu
- Laboratory for Gastrointestinal Secretions and Inflammation Research, Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria.,Laboratory for Gastrointestinal Secretions and Inflammation Research, Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Adeoti Gbemisola Adegoke
- Laboratory for Gastrointestinal Secretions and Inflammation Research, Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria.,Laboratory for Gastrointestinal Secretions and Inflammation Research, Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Samuel Babafemi Olaleye
- Laboratory for Gastrointestinal Secretions and Inflammation Research, Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria.,Laboratory for Gastrointestinal Secretions and Inflammation Research, Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria
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35
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Hassanzadeh P, Arbabi E, Atyabi F, Dinarvand R. Application of carbon nanotubes as the carriers of the cannabinoid, 2-arachidonoylglycerol: Towards a novel treatment strategy in colitis. Life Sci 2017; 179:66-72. [DOI: 10.1016/j.lfs.2016.11.015] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 11/09/2016] [Accepted: 11/20/2016] [Indexed: 12/25/2022]
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Cappelli APG, Zoppi CC, Silveira LR, Batista TM, Paula FM, da Silva PMR, Rafacho A, Barbosa-Sampaio HC, Boschero AC, Carneiro EM. Reduced glucose-induced insulin secretion in low-protein-fed rats is associated with altered pancreatic islets redox status. J Cell Physiol 2017; 233:486-496. [PMID: 28370189 DOI: 10.1002/jcp.25908] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Accepted: 03/13/2017] [Indexed: 01/01/2023]
Abstract
In the present study, we investigated the relationship between early life protein malnutrition-induced redox imbalance, and reduced glucose-stimulated insulin secretion. After weaning, male Wistar rats were submitted to a normal-protein-diet (17%-protein, NP) or to a low-protein-diet (6%-protein, LP) for 60 days. Pancreatic islets were isolated and hydrogen peroxide (H2 O2 ), oxidized (GSSG) and reduced (GSH) glutathione content, CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and catalase (CAT) gene expression, as well as enzymatic antioxidant activities were quantified. Islets that were pre-incubated with H2 O2 and/or N-acetylcysteine, were subsequently incubated with glucose for insulin secretion measurement. Protein malnutrition increased CAT mRNA content by 100%. LP group SOD1 and CAT activities were 50% increased and reduced, respectively. H2 O2 production was more than 50% increased whereas GSH/GSSG ratio was near 60% lower in LP group. Insulin secretion was, in most conditions, approximately 50% lower in LP rat islets. When islets were pre-incubated with H2 O2 (100 μM), and incubated with glucose (33 mM), LP rats showed significant decrease of insulin secretion. This effect was attenuated when LP islets were exposed to N-acetylcysteine.
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Affiliation(s)
- Ana Paula G Cappelli
- Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.,Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão (UFMA), São Luís, Maranhão, Brazil.,Department of Physiology and Biophysiology, Institute of Biomedical Sciences, University of Sao Paulo (USP), São Paulo, Brazil
| | - Claudio C Zoppi
- Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
| | - Leonardo R Silveira
- Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
| | - Thiago M Batista
- Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
| | - Flávia M Paula
- Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
| | | | - Alex Rafacho
- Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.,Department of Physiologic Sciences, Center of Biologic Sciences, Federal University of Santa Catarina (UFSC), Florianopolis, Santa Catarina, Brazil
| | - Helena C Barbosa-Sampaio
- Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
| | - Antonio C Boschero
- Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
| | - Everardo M Carneiro
- Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
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Pérez S, Taléns-Visconti R, Rius-Pérez S, Finamor I, Sastre J. Redox signaling in the gastrointestinal tract. Free Radic Biol Med 2017; 104:75-103. [PMID: 28062361 DOI: 10.1016/j.freeradbiomed.2016.12.048] [Citation(s) in RCA: 198] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2016] [Revised: 12/20/2016] [Accepted: 12/31/2016] [Indexed: 12/16/2022]
Abstract
Redox signaling regulates physiological self-renewal, proliferation, migration and differentiation in gastrointestinal epithelium by modulating Wnt/β-catenin and Notch signaling pathways mainly through NADPH oxidases (NOXs). In the intestine, intracellular and extracellular thiol redox status modulates the proliferative potential of epithelial cells. Furthermore, commensal bacteria contribute to intestine epithelial homeostasis through NOX1- and dual oxidase 2-derived reactive oxygen species (ROS). The loss of redox homeostasis is involved in the pathogenesis and development of a wide diversity of gastrointestinal disorders, such as Barrett's esophagus, esophageal adenocarcinoma, peptic ulcer, gastric cancer, ischemic intestinal injury, celiac disease, inflammatory bowel disease and colorectal cancer. The overproduction of superoxide anion together with inactivation of superoxide dismutase are involved in the pathogenesis of Barrett's esophagus and its transformation to adenocarcinoma. In Helicobacter pylori-induced peptic ulcer, oxidative stress derived from the leukocyte infiltrate and NOX1 aggravates mucosal damage, especially in HspB+ strains that downregulate Nrf2. In celiac disease, oxidative stress mediates most of the cytotoxic effects induced by gluten peptides and increases transglutaminase levels, whereas nitrosative stress contributes to the impairment of tight junctions. Progression of inflammatory bowel disease relies on the balance between pro-inflammatory redox-sensitive pathways, such as NLRP3 inflammasome and NF-κB, and the adaptive up-regulation of Mn superoxide dismutase and glutathione peroxidase 2. In colorectal cancer, redox signaling exhibits two Janus faces: On the one hand, NOX1 up-regulation and derived hydrogen peroxide enhance Wnt/β-catenin and Notch proliferating pathways; on the other hand, ROS may disrupt tumor progression through different pro-apoptotic mechanisms. In conclusion, redox signaling plays a critical role in the physiology and pathophysiology of gastrointestinal tract.
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Affiliation(s)
- Salvador Pérez
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjasot, 46100 Valencia, Spain
| | - Raquel Taléns-Visconti
- Department of Pharmacy and Pharmaceutical Technology and Parasitology, Faculty of Pharmacy, University of Valencia, Burjasot, 46100 Valencia, Spain
| | - Sergio Rius-Pérez
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjasot, 46100 Valencia, Spain
| | - Isabela Finamor
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjasot, 46100 Valencia, Spain
| | - Juan Sastre
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjasot, 46100 Valencia, Spain.
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38
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Saeed AL-Wajeeh N, Halabi MF, Hajrezaie M, M. Dhiyaaldeen S, Abdulaziz Bardi D, M. Salama S, Rouhollahi E, Karimian H, Abdolmalaki R, Azizan AHS, Mohd Ali H, Mohd Noor S, Abdulla MA. The Gastroprotective Effect of Vitex pubescens Leaf Extract against Ethanol-Provoked Gastric Mucosal Damage in Sprague-Dawley Rats. PLoS One 2016; 11:e0157431. [PMID: 27689880 PMCID: PMC5045201 DOI: 10.1371/journal.pone.0157431] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Accepted: 05/30/2016] [Indexed: 12/26/2022] Open
Abstract
Vitex pubescens is a Malaysian therapeutic plant employed in traditional drug to remedy a variety of disorders. The purpose of this research is to assess the gastroprotective efficiency of V. pubescens leaves against ethanol-induced gastric hemorrhagic laceration in rats. Animals were randomly allocated into seven groups and pre-treated, separately, with 10% Tween 20 (normal and ulcer control groups), 20 mg/kg omeprazole (reference group), and 62.5, 125, 250, and 500 mg/kg of V. pubescens extract (experimental groups). All animals were sacrificed after another hour. Histological evaluation of the ulcer control group revealed significant injury to the gastric mucosa with edema and leucocyte infiltration of the submucosal layer. PAS staining, showed remarkably intense magenta color, remarkable increase of HSP70 and decrease of Bax proteins in rats pre-treated with plant extracts compared to the ulcer control group. Gastric homogenates revealed a remarkable increase in endogenous antioxidant enzyme activities (CAT, SOD, GSH) and a decrease in the lipid peroxidation level (MDA) in animals pre-treated with V. pubescens extract compared with the ulcer control group. The gastroprotective activity of this plant might be related to increased antioxidant enzymes and decrease lipid peroxidation upsurge of HSP70 and reduced expression of Bax proteins.
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Affiliation(s)
- Nahla Saeed AL-Wajeeh
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Mohammed Farouq Halabi
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Maryam Hajrezaie
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Summaya M. Dhiyaaldeen
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Daleya Abdulaziz Bardi
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Suzy M. Salama
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Elham Rouhollahi
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Hamed Karimian
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Rojin Abdolmalaki
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | | | - Hapipah Mohd Ali
- Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Suzita Mohd Noor
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Mahmood Ameen Abdulla
- Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
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Takayama C, de-Faria FM, de Almeida ACA, Dunder RJ, Manzo LP, Socca EAR, Batista LM, Salvador MJ, Souza-Brito ARM, Luiz-Ferreira A. Chemical composition of Rosmarinus officinalis essential oil and antioxidant action against gastric damage induced by absolute ethanol in the rat. Asian Pac J Trop Biomed 2016. [DOI: 10.1016/j.apjtb.2015.09.027] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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40
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Sukalingam K, Jaarin K, Saad QHM, Mohamed S, Othman F. Consumption of ADD-X and Repeatedly Heated Palm Oil on the Blood Pressure and Oxidative Stress Markers in Ovarectmized Rats. INT J PHARMACOL 2016. [DOI: 10.3923/ijp.2016.514.522] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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41
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Viana AFSC, da Silva FV, Fernandes HDB, Oliveira IS, Braga MA, Nunes PIG, Viana DDA, de Sousa DP, Rao VS, Oliveira RDCM, Almeida Santos F. Gastroprotective effect of (-)-myrtenol against ethanol-induced acute gastric lesions: possible mechanisms. ACTA ACUST UNITED AC 2016; 68:1085-92. [PMID: 27291136 DOI: 10.1111/jphp.12583] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Accepted: 05/14/2016] [Indexed: 12/25/2022]
Abstract
OBJECTIVES (-)-Myrtenol is a natural fragrance monoterpenoid structurally related to α-pinene found in diverse plant essential oils. This study was aimed to assess the anti-ulcerogenic potential of (-)-myrtenol against ethanol-induced gastric lesions and to elucidate the underlying mechanism(s). METHODS Gastroprotective activity of (-)-myrtenol was evaluated using the mouse model of ethanol-induced gastric damage. To elucidate the gastroprotective mechanism(s), the roles of GABA, prostaglandins, nitric oxide and KATP channels were assessed. Besides, the oxidative stress-related parameters and the mucus content in gastric tissues were analysed. KEY FINDINGS (-)-Myrtenol at oral doses of 25, 50 and 100 mg/kg significantly decreased the severity of ethanol-induced gastric lesions affording gastroprotection that was accompanied by a decrease in the activity of myeloperoxidase and malondialdehyde, an increase in GPx, SOD, and catalase activity in gastric tissues, and with well-maintained normal levels of nitrite/nitrate, gastric mucus and NP-SHs. Pretreatment with GABA-A receptor antagonist flumazenil, the COX inhibitor indomethacin, and NO synthesis inhibitor L-NAME but not with KATP channel blocker glibenclamide significantly blocked the (-)-myrtenol gastroprotection. CONCLUSION These results provide first-time evidence for the gastroprotective effect of (-)-myrtenol that could be related to GABAA -receptor activation and antioxidant activity.
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Affiliation(s)
- Ana Flávia Seraine Custódio Viana
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.,Medicinal Plants Research Center, Health Sciences Center, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Francilene Vieira da Silva
- Medicinal Plants Research Center, Health Sciences Center, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Hélio de Barros Fernandes
- Medicinal Plants Research Center, Health Sciences Center, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Irisdalva Sousa Oliveira
- Medicinal Plants Research Center, Health Sciences Center, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Milena Aguiar Braga
- Postgraduate Program in Biotechnology, Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Odontology and Nursing, Federal University of the Ceará, Fortaleza, Ceará, Brazil
| | - Paulo Iury Gomes Nunes
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Daniel de Araújo Viana
- Laboratory of Pathology and Legal Medicine, Faculty of Veterinary Science, State University of Ceará, Fortaleza, Ceará, Brazil
| | | | - Vietla Satyanarayana Rao
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | | | - Flávia Almeida Santos
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
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Zádori ZS, Fehér Á, Tóth VE, Al-Khrasani M, Köles L, Sipos S, Del Bello F, Pigini M, Gyires K. Dual Alpha2C/5HT1A Receptor Agonist Allyphenyline Induces Gastroprotection and Inhibits Fundic and Colonic Contractility. Dig Dis Sci 2016; 61:1512-23. [PMID: 26860509 DOI: 10.1007/s10620-015-4026-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2015] [Accepted: 12/27/2015] [Indexed: 12/09/2022]
Abstract
BACKGROUND Allyphenyline, a novel α2-adrenoceptor (AR) ligand, has been shown to selectively activate α2C-adrenoceptors (AR) and 5HT1A receptors, but also to behave as a neutral antagonist of α2A-ARs. We exploited this unique pharmacological profile to analyze the role of α2C-ARs and 5HT1A receptors in the regulation of gastric mucosal integrity and gastrointestinal motility. METHODS Gastric injury was induced by acidified ethanol in Wistar rats. Mucosal catalase and superoxide dismutase levels were measured by assay kits. The effect of allyphenyline on electrical field stimulation (EFS)-induced fundic and colonic contractions was determined in C57BL/6 mice. RESULTS Intracerebroventricularly injected allyphenyline (3 and 15 nmol/rat) dose dependently inhibited the development of mucosal damage, which was antagonized by ARC 239 (α2B/C-AR and 5HT1A receptor antagonist), (S)-WAY 100135 (selective 5HT1A receptor antagonist), and JP-1302 (selective α2C-AR antagonist). This protection was accompanied by significant elevation of mucosal catalase and superoxide dismutase levels. Allyphenyline (10(-9)-10(-5) M) also inhibited EFS-induced fundic contractions, which was antagonized by ARC 239 and (S)-WAY 100135, but not by JP-1302. Similar inhibition was observed in the colon; however, in this case only ARC 239 reduced this effect, while neither selective inhibition of α2C-ARs and 5HT1A receptors nor genetic deletion of α2A- and α2B-ARs influenced it. CONCLUSIONS Activation of both central α2C-ARs and 5HT1A receptors contributes to the gastroprotective action of allyphenyline in rats. Its inhibitory effect on fundic contractions is mediated by 5HT1A receptors, but neither α2-ARs nor 5HT1A receptors take part in its inhibitory effect on colonic contractility in mice.
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Affiliation(s)
- Zoltán S Zádori
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., Budapest, 1089, Hungary
| | - Ágnes Fehér
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., Budapest, 1089, Hungary
| | - Viktória E Tóth
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., Budapest, 1089, Hungary
| | - Mahmoud Al-Khrasani
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., Budapest, 1089, Hungary
| | - László Köles
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., Budapest, 1089, Hungary
| | - Szabina Sipos
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., Budapest, 1089, Hungary
| | - Fabio Del Bello
- School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, via S. Agostino 1, 62032, Camerino, Italy
| | - Maria Pigini
- School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, via S. Agostino 1, 62032, Camerino, Italy
| | - Klára Gyires
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., Budapest, 1089, Hungary.
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Tarique M, Siddiqui HH, Khushtar M, Rahman MA. Protective effect of hydro-alcoholic extract of Ruta graveolens Linn. leaves on indomethacin and pylorus ligation-induced gastric ulcer in rats. J Ayurveda Integr Med 2016; 7:38-43. [PMID: 27297508 PMCID: PMC4910575 DOI: 10.1016/j.jaim.2015.09.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Revised: 07/10/2015] [Accepted: 09/25/2015] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND The search for an ideal and new antiulcer drug has been extended to herbals for novel molecules that decrease the incidence of relapse and afford better protection. OBJECTIVE The present study was designed to investigate the protective effect of hydro-alcoholic extract of Ruta graveolens (RGE) Linn. leaves on indomethacin (IND) and pylorus ligation-induced gastric ulcer in Wistar rats. MATERIALS AND METHODS The rats of all the six groups were deprived of food for 24 h. Then, the first group received 1 ml/kg/day p.o. of 1% carboxymethylcellulose calcium (CMC), second group 1 ml/kg/day p.o. of 1% CMC and third group 20 mg/kg/day p.o. of IND. Fourth and fifth groups received RGE 200 and 400 mg/kg/day p.o., respectively; while the sixth group 10 mg/kg/day p.o. omeprazole. After 30 min, last three groups received 20 mg/kg/day p.o. of IND also. All these treatments after food deprivation were repeated each day for 5 consecutive days. Pylorus ligation was performed on 6th day in last five groups. After 4 h, stomach by sacrifice of the rats was examined for ulcer index (UI) and gastric mucus. Gastric juice was assessed for acidity, pH and pepsin; while gastric tissues were assessed for thiobarbituric acid reactive substance (TBARS) and glutathione (GSH). RESULTS Fifth group showed significant decrease in UI (10.33 ± 0.67), TBARS (0.33 ± 0.03 mmol/mg), free acidity (48.78 ± 5.12 meq/l/100 g), total acidity (99.33 ± 9.31 meq/l/100 g), and pepsin activity (8.47 ± 0.41 μg/ml) levels while it showed significant increase in mucus (412.4 ± 21.6 μg/g), GSH (57.9 ± 4.8 mmol/mg) and pH (3.32 ± 0.27) compared to third group. Percent protection in RGE 400 mg was found to be 63.32 compared to indomethacin. CONCLUSION RGE possesses antiulcerogenic activity as it exhibits protective effect on gastric ulcer in rats.
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Affiliation(s)
- Mohd Tarique
- Department of Pharmacy, Faculty of Pharmacy, Bioactive Research Laboratory, Integral University, Lucknow, Uttar Pradesh, India
| | - Hefazat H Siddiqui
- Department of Pharmacy, Faculty of Pharmacy, Bioactive Research Laboratory, Integral University, Lucknow, Uttar Pradesh, India
| | - Mohd Khushtar
- Department of Pharmacy, Faculty of Pharmacy, Bioactive Research Laboratory, Integral University, Lucknow, Uttar Pradesh, India.
| | - Md Azizur Rahman
- Department of Pharmacy, Faculty of Pharmacy, Bioactive Research Laboratory, Integral University, Lucknow, Uttar Pradesh, India
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Antioxidant and anti-aging activities of polysaccharides from Calocybe indica var. APK2. ACTA ACUST UNITED AC 2016; 68:329-34. [PMID: 27174669 DOI: 10.1016/j.etp.2016.04.001] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2015] [Revised: 03/09/2016] [Accepted: 04/23/2016] [Indexed: 11/23/2022]
Abstract
The crude polysaccharides were extracted from the fruiting bodies of Calocybe indica (CIP). The antioxidant activities of CIP were evaluated both in vitro and in vivo. Chemical characteristics of the polysaccharides were investigated. In in vitro antioxidant assay, CIP showed noticeable 2,2-diphenyl-1-picryl-hydrazyl (DPPH), hydroxyl radical scavenging activities, reducing power and lipid peroxidation inhibition. Chemical analysis showed the presence of carbohydrate, protein and the FTIR spectra revealed the presence of general characteristic absorption peak of the polysaccharides. For in vivo antioxidant activity, two different doses of CIP were orally administrated over a period of 6 weeks in a d-galactose (d-gal) induced aged mice model. Significantly lowered activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), levels of glutathione (GSH) and elevated malondialdehyde (MDA) levels were observed in brain and serum of d-galactose induced rats, when compared to control rats. Administration of CIP significantly raised the activities of SOD, CAT, GPx, levels of GSH and lowered the levels of MDA in mice brain and serum in a dose-dependent manner. The results suggested that CIP had potent antioxidant activity and could minimize the occurrence of age-associated disorders associated with involvement of free radicals.
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Liu J, Sun D, He J, Yang C, Hu T, Zhang L, Cao H, Tong AP, Song X, Xie Y, He G, Guo G, Luo Y, Cheng P, Zheng Y. Gastroprotective effects of several H2RAs on ibuprofen-induced gastric ulcer in rats. Life Sci 2016; 149:65-71. [DOI: 10.1016/j.lfs.2016.02.045] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 01/29/2016] [Accepted: 02/10/2016] [Indexed: 11/28/2022]
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46
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Engineering Behavior and Characteristics of Water-Soluble Polymers: Implication on Soil Remediation and Enhanced Oil Recovery. SUSTAINABILITY 2016. [DOI: 10.3390/su8030205] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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47
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Carvalho NS, Silva MM, Silva RO, Nicolau LAD, Araújo TSL, Costa DS, Sousa NA, Souza LKM, Soares PMG, Medeiros JVR. Protective Effects of Simvastatin Against Alendronate-Induced Gastric Mucosal Injury in Rats. Dig Dis Sci 2016; 61:400-9. [PMID: 26403426 DOI: 10.1007/s10620-015-3890-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Accepted: 09/17/2015] [Indexed: 01/05/2023]
Abstract
BACKGROUND It has been reported that simvastatin, a statin commonly prescribed for its anti-inflammatory and antioxidant effects, has gastroprotective effects in indomethacin and ethanol-induced gastric ulcers. However, the effects of simvastatin on alendronate-induced gastric mucosal injury remain unexplored. AIM This study investigated the use of simvastatin for the treatment of alendronate-induced gastric ulcers in rats. METHODS Female rats were pretreated with vehicle or simvastatin (20 and 60 mg/kg p.o.). After 1 h, the rats received alendronate (50 mg/kg p.o.). Simvastatin was administered once daily for 7 days, and from the fourth day of simvastatin treatment, alendronate was administered once daily for 4 days. On the final day of treatment, 4 h after alendronate administration, animals were euthanized, their stomachs were removed, and gastric damage was measured. Samples of the stomach were fixed in 10 % formalin immediately after their removal for subsequent histopathological assessment. Unfixed samples were weighed, frozen at -80 °C until assayed for glutathione (GSH), malondialdehyde (MDA), and cytokine levels and myeloperoxidase (MPO) activity. A third group was used to measure mucus and gastric secretion. RESULTS Pretreatment with simvastatin prevented alendronate-induced macroscopic gastric damage and reduced the levels of MDA and GSH, TNF-α and IL-1β, MPO activity, and mucus levels, in the stomach. CONCLUSIONS This study demonstrates the protective effects of simvastatin against alendronate-induced gastric ulceration. Maintenance of mucosal integrity, inhibition of neutrophil activity, and reduced oxidative stress associated with decreased gastric acidity may explain the gastroprotective effects of simvastatin.
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Affiliation(s)
- Nathalia S Carvalho
- Post Graduation Program in Pharmacology, Medicinal Plant Research Center (NPPM), Federal University of Piauí, Teresina, PI, Brazil
| | - Mônica M Silva
- Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil
| | - Renan O Silva
- Laboratory of Pharmacology of Inflammation and Cancer (LAFICA), Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Lucas A D Nicolau
- Laboratory of Pharmacology of Inflammation and Cancer (LAFICA), Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Thiago S L Araújo
- Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil
| | - Douglas S Costa
- Post Graduation Program in Pharmacology, Medicinal Plant Research Center (NPPM), Federal University of Piauí, Teresina, PI, Brazil
| | - Nayara A Sousa
- Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil
| | - Luan K M Souza
- Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil
| | - Pedro M G Soares
- Laboratory of Pharmacology of Inflammation and Cancer (LAFICA), Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Jand Venes R Medeiros
- Post Graduation Program in Pharmacology, Medicinal Plant Research Center (NPPM), Federal University of Piauí, Teresina, PI, Brazil. .,Post Graduation Program in Biotechnology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, PI, Brazil. .,BIOTEC/LAFFEX/UFPI, Av. São Sebastião, no. 2819, Parnaíba, PI, CEP 64202-020, Brazil.
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48
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Hermes TDA, Macedo AB, Fogaça AR, Moraes LHR, de Faria FM, Kido LA, Cagnon VHA, Minatel E. Beneficial cilostazol therapeutic effects inmdxdystrophic skeletal muscle. Clin Exp Pharmacol Physiol 2016; 43:259-67. [DOI: 10.1111/1440-1681.12521] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Revised: 11/17/2015] [Accepted: 11/25/2015] [Indexed: 11/28/2022]
Affiliation(s)
- Túlio de Almeida Hermes
- Department of Structural and Functional Biology; Institute of Biology; State University of Campinas (UNICAMP); Campinas São Paulo Brazil
| | - Aline Barbosa Macedo
- Department of Structural and Functional Biology; Institute of Biology; State University of Campinas (UNICAMP); Campinas São Paulo Brazil
| | - Aline Reis Fogaça
- Department of Structural and Functional Biology; Institute of Biology; State University of Campinas (UNICAMP); Campinas São Paulo Brazil
| | - Luis Henrique Rapucci Moraes
- Department of Structural and Functional Biology; Institute of Biology; State University of Campinas (UNICAMP); Campinas São Paulo Brazil
| | - Felipe Meira de Faria
- Department of Structural and Functional Biology; Institute of Biology; State University of Campinas (UNICAMP); Campinas São Paulo Brazil
| | - Larissa Akemi Kido
- Department of Structural and Functional Biology; Institute of Biology; State University of Campinas (UNICAMP); Campinas São Paulo Brazil
| | - Valéria Helena Alves Cagnon
- Department of Structural and Functional Biology; Institute of Biology; State University of Campinas (UNICAMP); Campinas São Paulo Brazil
| | - Elaine Minatel
- Department of Structural and Functional Biology; Institute of Biology; State University of Campinas (UNICAMP); Campinas São Paulo Brazil
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Antonisamy P, Arasu MV, Dhanasekaran M, Choi KC, Aravinthan A, Kim NS, Kang CW, Kim JH. Protective effects of trigonelline against indomethacin-induced gastric ulcer in rats and potential underlying mechanisms. Food Funct 2016; 7:398-408. [PMID: 26499137 DOI: 10.1039/c5fo00403a] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
The present study was undertaken to explore gastroprotective effects of trigonelline (TRG) and to determine the potential mechanisms involved in this action. In order to evaluate the gastroprotective efficiency of TRG, an indomethacin-induced ulcer model has been applied. Antioxidants, cytokines, adhesion markers and apoptosis levels have been analyzed for the biochemical mechanism involved in TRG activity. TRG (45 mg kg(-1)) pretreated rats significantly inhibited gastric lesions by 81.71%. Indomethacin administration raises the levels of leukotriene B4 (LTB4), lipid peroxidation and myeloperoxidase (MPO) with the significant declines of prostaglandin E2 (PGE2), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px) levels. Conversely, TRG (45 mg kg(-1)) pretreated animals showed significant rises in PGE2 and antioxidant levels along with substantial reductions in LTB4, lipid peroxidation and MPO levels. Indomethacin-induced rats also exhibited considerable increases of pro-inflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) levels and decreases of anti-inflammatory cytokines such as interleukin-10 (IL-10) and interleukin-4 (IL-4), but these imbalances were normalized through treatment of TRG. The protective activity of TRG against indomethacin-induced gastric ulcer has been ascribed to three important mechanisms: (1) anti-inflammatory; (2) antioxidant; (3) anti-apoptotic pathways.
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Affiliation(s)
- Paulrayer Antonisamy
- College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, 54596 79 Gobong-ro, Iksan-city, Jeollabuk-Do, Republic of Korea.
| | - Mariadhas Valan Arasu
- Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Muniappan Dhanasekaran
- Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600 034, Tamil Nadu, India
| | - Ki Choon Choi
- Grassland and forage division, National Institute of Animal Science, RDA, Seonghwan-Eup, Cheonan-Si, Chungnam 330-801, Republic of Korea
| | - Adithan Aravinthan
- College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, 54596 79 Gobong-ro, Iksan-city, Jeollabuk-Do, Republic of Korea.
| | - Nam Soo Kim
- College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, 54596 79 Gobong-ro, Iksan-city, Jeollabuk-Do, Republic of Korea.
| | - Chang-Won Kang
- College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, 54596 79 Gobong-ro, Iksan-city, Jeollabuk-Do, Republic of Korea.
| | - Jong-Hoon Kim
- College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University, 54596 79 Gobong-ro, Iksan-city, Jeollabuk-Do, Republic of Korea.
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50
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Atalay F, Odabasoglu F, Halici M, Cadirci E, Aydin O, Halici Z, Cakir A. N-Acetyl Cysteine Has Both Gastro-Protective and Anti-Inflammatory Effects in Experimental Rat Models: Its Gastro-Protective Effect Is Related to Its In Vivo and In Vitro Antioxidant Properties. J Cell Biochem 2015; 117:308-19. [DOI: 10.1002/jcb.25193] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Accepted: 04/09/2015] [Indexed: 12/15/2022]
Affiliation(s)
- Fadime Atalay
- Department of Medical Biochemistry, Faculty of Medicine; Kafkas University; Kars 36100 Turkey
| | - Fehmi Odabasoglu
- Department of Medical Biochemistry, Faculty of Medicine; Kafkas University; Kars 36100 Turkey
| | - Mesut Halici
- Department of Biochemistry, Faculty of Veterinary; Ataturk University; Erzurum 25240 Turkey
| | - Elif Cadirci
- Department of Pharmacology, Faculty of Pharmacy; Ataturk University; Erzurum 25240 Turkey
| | - Ozlem Aydin
- Department of Biochemistry, Faculty of Pharmacy; Ataturk University; Erzurum 25240 Turkey
| | - Zekai Halici
- Department of Pharmacology, Faculty of Medicine; Ataturk University; Erzurum 25240 Turkey
| | - Ahmet Cakir
- Department of Chemistry, Faculty of Science and Art; Kilis 7 Aralık University; Kilis 79100 Turkey
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