Effect of methionine on hepatotoxicity due to co-administration of gentamicin and indomethacin in rats

Synchronous administration of gentamicin and indomethacin is, sometimes, a necessity. However, the effect of this treatment on the liver and the possible effect of methionine on their hepatotoxicity have not been studied well. This study was performed on 42 male Sprague Dawley rats to elucidate the effect of combined treatment with gentamicin and indomethacin and the potential effect of methionine on their hepatotoxicity. Rats were divided into six equal groups randomly and were injected with normal saline, gentamicin, indomethacin, gentamicin and indomethacin, methionine, and a combination of three above-mentioned treatments for 14 days. Twenty-four hours after the last injection, blood samples were taken for measuring AST and ALT. Histopathologic and biochemical evaluations have shown severe hyperemia in the indomethacin group but no significant changes in AST or ALT. Gentamicin-administered rats have shown mild hyperemia, capillarization of sinusoids, deformed and acidophilic hepatocytes, and apoptosis and infiltration of mononuclear cells in the parenchyma and portal area. These changes were associated with elevated levels of AST and ALT. Co-administration of gentamicin and indomethacin has resulted in the development of various lesions in liver structure and enhanced concentrations of AST and ALT, while administration of methionine with the two other agents ameliorated these changes as evidenced by a mild hyperemia observed in hepatic tissue and no significant changes in AST and ALT. Methionine-treated rats, as rats injected by normal saline, have shown no pathologic lesion and no liver enzyme activity augmentation. The obtained results revealed that gentamicin may aggravate indomethacin hepatotoxicity, and methionine managed to ameliorate this effect.