Effect of phenobarbital or pregnenolone-16alpha-carbonitrile (PCN) pretreatment on acute carbon tetrachloride hepatotoxicity in rats

In rats, CCl₄ hepatotoxicity (reflected by augmented serum glutamic-pyruvic transaminase activity and hepatic triglyceride content) was diminished by pregnenolone-16α-carbonitrile (PCN) and markedly increased by phenobarbital. PCN, like penobarbital, caused smooth-surfaced endoplasmic reticulum proliferation in hepatocytes and enhanced hexobarbital oxidation, ethylmorphine N-demethylation, cytochrome P-450 and NADPH-cytochrome c reductase activity. Contrary to earlier views, it is concluded that the increase in these parameters is not a prerequisite for augmented CCl₄ toxicity. Perhaps the cytochrome P-450 induced by the steroid and barbiturate has different catalytic properties, which are responsible for variations in the response to CCl₄.