title: Carbonyl traps as potential protective agents against methimazole-induced liver injury.
abstract: Liver injury is a deleterious adverse effect associated with methimazole administration, and reactive intermediates are suspected to be involved in this complication. Glyoxal is an expected reactive intermediate produced during methimazole metabolism. Current investigation was undertaken to evaluate the role of carnosine, metformin, and N-acetyl cysteine as putative glyoxal (carbonyl) traps, against methimazole-induced hepatotoxicity. Methimazole (100 mg/kg, intraperitoneally) was administered to intact and/or glutathione (GSH)-depleted mice and the role of glyoxal trapping agents was investigated. Methimazole caused liver injury as revealed by an increase in serum alanine aminotransferase and aspartate aminotransferase. Moreover, lipid peroxidation and protein carbonylation occurred significantly in methimazole-treated animals' liver. Hepatic GSH reservoirs were decreased, and inflammatory cells infiltration was observed in liver histopathology. Methimazole-induced hepatotoxicity was severe in GSH-depleted mice and accompanied with interstitial hemorrhage and necrosis of the liver. Glyoxal trapping agents effectively diminished methimazole-induced liver injury both in intact and/or GSH-depleted animals.
authors.affiliation: Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Gerash School of Paramedical Sciences, Shiraz University of Medical Sciences, Gerash, Iran. rezaheidari@hotmail.com.
authors.forename: Reza
authors.initials: R
authors.lastname: Heidari
authors.forename: Hossein
authors.initials: H
authors.lastname: Niknahad
authors.forename: Akram
authors.initials: A
authors.lastname: Jamshidzadeh
authors.forename: Negar
authors.initials: N
authors.lastname: Azarpira
authors.forename: Mandana
authors.initials: M
authors.lastname: Bazyari
authors.forename: Asma
authors.initials: A
authors.lastname: Najibi
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002336:Carnosine / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008713:Methimazole / Q000633:toxicity*; D051379:Mice; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000627:therapeutic use
chemical_list: D020011:Protective Agents; D008713:Methimazole; D002336:Carnosine; D008687:Metformin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000111:Acetylcysteine
keywords: Antithyroid Drugs; Drug-Induced Liver Injury (DILI); Endocrinology; Glyoxal; Reactive Metabolite