Differential acute effects of phenobarbital and 3-methylcholanthrene pretreatment on CCl 4 -induced hepatotoxicity in rats

Phenobarbital (PB) pretreatment significantly enhanced the rise in SGOT and SGPT activity immediately after a 3 hr exposure of rats to CCl₄ by inhalation. However, these parameters of hepatotoxicity were significantly lower in rats pretreated with 3-methylcholanthrene (MC) when compared to rats pretreated with the vehicle and exposed to CCl₄ vapor. Hepatic microsomal NADPH cytochrome c reductase activity and the amount of CO-binding pigment were elevated by PB pretreatment, but MC had no effect on hepatic microsomal NADPH cytochrome c reductase activity. Although CCl₄ exposure reduced CO-binding pigment content by 61% in PB pretreated and by 39% in MC-pretreated rats, microsomal NADPH cytochrome c reductase activity was reduced by only 6% and 20%, respectively. At 21 hr after exposure to CCl₄, the difference in SGOT and SGPT values of the PB and MC pretreated rats was more divergent. Histologic evidence at this time revealed extensive damage in the PB pretreated animals and a sparing effect in the MC pretreated animals. The differential effects of MC and PB pretreatment on NADPH cytochrome c reductase activity and CO-binding pigment content may be responsible for the observed protective effect of MC in CCl₄ exposed rats.