The role of enzyme induction and inhibition on cypermethrin hepatotoxicity

Cypermethrin at different concentrations (100, 200, 400 and 800 ng ml (-1)) was incubated with a primary culture of rat hepatocytes. Cypermethrin was cytotoxic to rat hepatocytes at concentrations of 200 ng ml(-1) or greater. Toxicity was measured by a decrease in cell viability and leakage of ALT a nd AST enzymes into the culture medium. The role of cytochrome P450 in the hepatotoxicity of cypermethrin insecticide was investigated in fresh hepato cytes isolated either from phenobarbital pretreated rats or control rats an d coincubated with SKF525A. Pretreatment with phenobarbital strongly protec ted the hepatocytes against the cypermethrin induced loss of cell viability percentage and increased enzyme leakage percentage. Coincubation of the he patocytes with SKF525A, a well-known cytochrome P450 inhibitor, substantial ly potentiated the effect of cypermethrin on cell viability and enzyme leak age. These results suggest that the cytocidal hepatotoxicity of cypermethri n in primary hepatocyte culture depends on its parent compound and phenobar bital, as a cytochrome P450 inducer, could be of therapeutic value. (C) 200 1 Academic Press.