Potentiating effect of rifampicin on methimazole induced hepatotoxicity in mice

Abstract

Methimazole (MMI) is a widely used drug for hyperthyroidism. However, its clinical use is associated with hepatotoxicity. Though the precise mechanism of hepatic damage is still far from clear, role of metabolic activation and reactive metabolites have been implicated. The present study was designed to investigate the role of enzyme induction in bioactivation based hepatotoxicity of methimazole in mice. Thirty male mice were randomly divided into five groups. Hepatotoxicity was induced by single intraperitoneal injection of methimazole (1000mg/kg). Pretreatment with rifampicin which is a potent enzyme inducer was carried out for 6 days prior to administration of methimazole. The extent of hepatic damage was determined by measuring serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) along with histopathological grading of liver samples. The elevated levels of biochemical markers by methimazole were potentiated by pretreatment with rifampicin. This potentiation of hepatic injury was also observed in liver histopathological examination. These findings suggest induction of microsomal enzymes as a potentiating factor of methimazole induced hepatotoxicity.