Effects of cytochrome P-450 inhibitors and inducers on CCl4 toxicity in primary hepatocyte cultures from mongolian gerbils.

Abstract

The influence of the incubation period and the effects of cytochrome P-450 (CYP) inhibitors and inducers on CCl4 toxicity in gerbil hepatocyte cultures were studied. The prolonged incubation of gerbil hepatocyte cultures after seeding was less sensitive to CCl4-induced toxicity and affected the immunostainability of some CYP apoproteins. SKF-525A and chloramphenicol (CPC), which are CYP inhibitors, had significant protective effects on the CCl4-induced T-Chol increase and enzyme leakage. 3-Methylcholanthrene (3-MC) and clofibric acid (CFA) enhanced the CCl4 toxicity, increasing LDH leakage and intracellular contents of TG and T-Chol. 3-MC and CFA treated cells were intensely positive for multi-isoform of CYPs. Ethanol (EtOH) also enhanced the CCl4-induced enzyme leakage and cytoplasmic vacuolation without fatty changes, and increased only CYP2EI staining level within cells. This study revealed that CCl4-induced toxicity in gerbil hepatocytes also depends on some CYP activities.