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Carbonyl Traps as Potential Protective Agents against Methimazole‑Induced Liver Injury
Author(s) -
Heidari Reza,
Niknahad Hossein,
Jamshidzadeh Akram,
Azarpira Negar,
Bazyari Mandana,
Najibi Asma
Publication year - 2015
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21682
Subject(s) - chemistry , glutathione , methimazole , liver injury , glyoxal , pharmacology , endocrinology , antithyroid agent , lipid peroxidation , medicine , biochemistry , oxidative stress , thyroid , enzyme , organic chemistry , graves' disease
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.