Toxicity and toxicokinetics of MeISP in isolated rat hepatocytes

Toxicity and toxicokinetics of a new organophosphorus insecticide, MeISP, in isolated rat hepatocytes were studied. It was found that at the final concentration of 1.5 mmol/L, MeISP can (1) result in an increase of leakage of intracellular enzymes, alanine amino-transferase (ALT), lactate dehydrogenase (LDH), beta-glucuronidase (beta-GDase) and acid phosphatase (AcP) to the medium in a dose-dependent fashion; (2) give rise to obvious plasma membrane blebbing; (3) rapidly deplete the intracellular GSH and (4) almost completely inhibit the protein synthesis and gluconeogenesis from sodium pyruvate. The kinetics study showed that at the final concentration of 15 mumol/L, MeISP is rapidly metabolized and this process fits the one-compartment model. The metabolism of MeISP in the hepatocytes with phenobarbital-induced microsomal enzymes is accelerated. These results indicate that (1) MeISP has obvious toxicity to isolated rat hepatocytes and isolated hepatocytes provide a suitable system to examine the toxic effects of xenobiotics at the cellular level and (2) MeISP is metabolized mainly by microsomal enzymes.