Effect of 4-methylpyrazole and pyrazole on the induction of fatty liver by a single dose of ethanol

Abstract

Pyrazole (272 mg/kg), 4-methylpyrazole (4-MP; 200 mg/kg) or saline was injected intraperitoneally into fasted male and female rats. Ten min later, ethanol (4 or 6 g/kg) or an equicaloric dose of sucrose was given by stomach tube. Hepatic triglyceride (TG) levels were measured at 6, 12 or 16 hr after the gavage. With a 4 g/kg dose of ethanol, pyrazole reduced the accumulation of TG at 6 hr in females, but not at 12 and 16 hr. In males, ethanol gave relatively little TG accumulation at 6 hr and pyrazole did not affect this, but at 16 hr the TG levels in the ethanol-pyrazole group had not risen as much as in the ethanol-saline group. In contrast to pyrazole, 4-MP by itself increased liver TG content, and significantly increased the TG accumulation caused by a 4 g/kg dose of ethanol in both males and females at 16 hr. However, 4-MP caused a significantly smaller TG accumulation in females at 6 hr after the ethanol, but not in males. With a larger dose of ethanol (6 g/kg), both pyrazole and 4-MP decreased the accumulation of TG at 16 hr in males. It is concluded that ethanol per se, ethanol as a metabolic substrate, and pyrazoles as pharmacological agents with complex actions may all contribute to the development of acute fatty liver. Therefore, pyrazole and 4-MP do not appear to be suitable tools for resolving the controversy about the mechanism of production of alcoholic fatty liver.