title: Hepatoprotective potential of glyceryl trinitrate against chemically induced oxidative stress and hepatic injury in rats.
abstract: Glyceryl trinitrate (GTN) has been used widely as a potent vasodilator to treat heart conditions, such as angina pectoris and chronic heart failure. This study aims to elucidate the effect of exogenous nitric oxide (NO) administration, using GTN, on carbon tetrachloride (CCl4)-induced oxidative stress and liver injury in rats. The results obtained demonstrated that NO generated by the administration of GTN affords protection against CCl4-induced oxidative stress and liver injury. Administration of CCl4resulted in a significant ( p < 0.001) increase in lipid peroxidation and tissue damage markers (aspartate and alanine transaminase and lactate dehydrogenase) release in serum. Parallel to these changes, CCl4also caused downregulation of antioxidant enzymes including glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST), and several fold induction in γ-glutamyl transpeptidase (GGT) activity. Subsequent administration of GTN resulted in significant ( p < 0.001) recovery of GSH-metabolizing enzymes in a dose-dependent manner. Further, administration of NO inhibitor, NG-nitro-l-arginine methyl ester (l-NAME), exacerbated CCl4-induced oxidative tissue injury. Overall, the study suggests that GTN might suppress oxidant-induced tissue injury and hepatotoxicity in rats.
authors.affiliation: 1 Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rahman
authors.affiliation: 2 Department of Pathology, Jawaharlal Nehru Medical College, AMU Aligarh, UP, India.
authors.forename: S M
authors.initials: SM
authors.lastname: Vasenwala
authors.affiliation: 3 Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, Sabah, Malaysia.
authors.forename: M
authors.initials: M
authors.lastname: Iqbal
mesh_terms: D000410:Alanine Transaminase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000235:genetics / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*; D005723:gamma-Glutamyltransferase / Q000235:genetics / Q000378:metabolism
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005996:Nitroglycerin; D019331:NG-Nitroarginine Methyl Ester
keywords: Glyceryl trinitrate; NG-nitro-l-arginine methyl ester; hepatotoxicity; liver damage; nitric oxide; oxidative stress