Effect of pyrazole on the induction of fatty liver by chronic administration of ethanol

Abstract

Groups of rats were pair-fed liquid diets containing ethanol or an equicaloric concentration of sucrose for a period of 3–4 weeks. Half of the animals on each diet also received by gavage a dose (37·5 mg/kg) of pyrazole every second day. On this treatment all animals maintained their weight and appeared healthy, but those receiving pyrazole plus ethanol had consistently higher blood ethanol levels than those receiving ethanol alone. At the end of the treatment period, the pyrazole-ethanol groups were found to have much higher hepatic triglyceride levels than those on ethanol alone, except when ethanol contributed only 20 per cent to the caloric intake. In contrast, animals receiving pyrazole plus sucrose had less hepatic triglyceride than those on sucrose alone, when fat contributed substantially to the diet. The findings suggest that pyrazole itself tends to reduce hepatic triglyceride by an as yet unknown mechanism, but enhances a direct hepatotoxic effect of ethanol by impairing its metabolism and prolonging the period of exposure of the liver to ethanol. However, other mechanisms of synergism between ethanol and pyrazole cannot be ruled out.