title: Diosmin protects against ethanol-induced hepatic injury via alleviation of inflammation and regulation of TNF-α and NF-κB activation.
abstract: The present investigation was designed to evaluate the efficacy of diosmin against ethanol-induced hepatotoxicity in rats by modulating various mechanisms including ethanol metabolizing enzymes, generation of free radicals, imbalance in oxidant-antioxidant status, oxidative damage to membrane lipids, activation of transcription factors and elevation in inflammatory markers involved in ethanol-induced hepatic damage. Diosmin is a flavone glycoside, having anti-inflammatory and anti-cancer properties. Thirty female Wistar rats segregated in five groups, each with six animals. Group I as control followed by Group II, III and IV were treated with ethanol for 28 days. While groups III and IV were administered with diosmin at 10 mg/kg b wt (D1) and 20 mg/kg b wt (D2) respectively prior to ethanol administration. Group V was given only higher dose of diosmin. In ethanol-treated group, ethanol metabolizing enzymes viz., CYP 450 2E1 and alcohol dehydrogenase (ADH) significantly increased by 77.82% and 32.32% in liver tissues respectively as compared with control group and this enhancement is significantly normalized with diosmin administration. Diosmin administration (D1 & D2) significantly (p < 0.001) attenuates oxidative stress markers i.e., LPO, GSH, GPx, GR and XO by 90.77 & 137.55%, 17.18 & 25%, 37.3 & 49.86%, 21.63 & 44.9% and 56.14 &77.19% respectively. Serum ALT, AST and LDH significantly increased by 102.03, 116.91 and 45.20% in ethanol-treated group as compared with control group. Group III and IV animals showed significant reduction in the serum toxicity markers. Diosmin further alleviated ethanol-induced NF-κB activation, enhanced expression of TNF-α, COX-2 and iNOS. Findings from the present study permit us to conclude that diosmin alleviates alcoholic liver injury via modulating ethanol metabolizing pathway, inhibition of oxidative stress markers and suppression of inflammatory markers. This may represent a novel protective strategy against ethanol-induced liver diseases.
authors: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors: Mir
authors: M
authors: Tahir
authors: Muneeb U
authors: MU
authors: Rehman
authors: Abdul
authors: A
authors: Lateef
authors: Rehan
authors: R
authors: Khan
authors: Abdul Quaiyoom
authors: AQ
authors: Khan
authors: Wajhul
authors: W
authors: Qamar
authors: Farrah
authors: F
authors: Ali
authors: Oday
authors: O
authors: O'Hamiza
authors: Sarwat
authors: S
authors: Sultana
mesh_terms: D000426:Alcohol Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000187:drug effects / Q000502:physiology; D019392:Cytochrome P-450 CYP2E1 / Q000187:drug effects / Q000378:metabolism; D004145:Diosmin / Q000008:administration & dosage*; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D007249:Inflammation / Q000188:drug therapy*; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D008108:Liver Diseases, Alcoholic / Q000517:prevention & control*; D016328:NF-kappa B / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000502:physiology
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D004145:Diosmin; D000426:Alcohol Dehydrogenase; D002374:Catalase; D019392:Cytochrome P-450 CYP2E1; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2