Increased hepatotoxicity of carbon tetrachloride by the hypolipidemic drug nafenopin in rats.

Pretreatment of rats with the potent hypolipidemic drug nafenopin enhanced the hepatotoxicity of carbon tetrachloride as judged by the serum activity of glutamic pyruvic transaminase (SGPT), hepatic triglyceride content and glucose-6-phosphatase activity as well as by light and electronmicroscopy. Nafenopin alone caused an increase in liver weight, proliferation of peroxisomes and of smooth endoplasmic reticulum in hepatocytes. No marked changes of serum SGPT activity were observed, but hepatic glucose-6-phosphatase activity decreased. Results suggest that the hypolipidemic compound can act on endoplasmic reticulum membranes so that they become more susceptible to the attack by carbon tetrachloride or it(s) metabolite(s).