Effects of drug metabolism modifiers on pulegone-induced hepatotoxicity in mice

Intraperitoneal injection of R-(+)-pulegone (pulegone), the main constituent of pennyroyal oil, to ddY mice caused extensive liver injury as characterized by an increase in serum glutamic pyruvic transaminase (GPT) activity and centrilobular necrosis of hepatocytes. Treatments of mice with the cytochrome P-450 enzyme inhibitors, SKF-525A, metyrapone, piperonyl butoxide, and carbon disulfide (CS2), prevented or markedly alleviated the hepatotoxicity of pulegone. These results are compatible with the view that some metabolite of pulegone is responsible for the liver injury in mice.