Hepatotoxic effects of anti-rheumatic drugs in cultured rat hepatocytes.

Drug-induced liver injury has been suggested as a possible mechanism for the liver damage in rheumatic diseases. To evaluate the role of direct toxic action of drugs on hepatocytes, the effects of salicylate, chloroquine, prednisolone and indomethacin on LDH leakage from cultured rat hepatocytes were studied. Exposure for 24 h to the first two drugs induced liver damage, as reflected by LDH release, at concentrations 2-10 times as high as the therapeutic plasma levels in humans. Indomethacin and prednisolone at concentrations approx 50-100-fold higher than the therapeutic plasma levels, were not toxic to cultured hepatocytes. The data suggest that direct a toxic effect on hepatocytes is one possible mechanism of hepatotoxicity for salicylate and chloroquine, especially since the exposure time is much longer in humans than in the experimental model used here.