Chloroform-induced oxidative stress in rat liver: Implication of metallothionein

Abstract

Current studies evaluated the effect of acute and subacute exposure to chloroform (CHCl₃) on rat liver and the implication of oxidative stress. For this purpose, different doses of CHCl₃ (150, 300 and 450 mg/kg bw) were administered intraperitoneally (ip) to male Wistar rats. Malondialdehyde (MDA), glutathione (GSH), reduced cytochrome c and metallothioneins (MTs) levels as well as the activities of catalase (CAT) and glutathione peroxidase (GPx) and the activities of the biochemical markers of hepatic injury (alanine transaminase [ALT] and aspartate transaminase [AST]) were determined. CHCl₃ did not cause a significant increase in hepatic lipid peroxidation. However, dose-dependant and/or time dependant effects of CHCl₃ were demonstrated on most of the oxidative stress parameters measured, namely the GSH depletion and the superoxide anion production. Acute exposure CHCl₃ increased the aminotransferase and GPx activities and reduced cytochrome c levels in a dose-dependant pattern. A well-combined dose-dependent and time-dependent effect of CHCl₃ on MT levels after acute and subacute exposure was noticed. Moreover, the increase of MT levels seems to be associated with the GSH depletion, indicating a possible role of the latter in MT synthesis. In conclusion, the superoxide anion production and the GSH depletion could be implicated in the mechanism of hepatotoxity of CHCl₃ and MTs seem to be a part of the antioxidant defense system against the oxidative damage caused by CHCl₃ in liver.