EFFECTS OF RO-31-8220 ON LIPOPOLYSACCHARIDES-INDUCED HEPATOTOXICITY AND RELEASE OF TUMOR-NECROSIS-FACTOR FROM RAT KUPFFER CELLS

AIM: To investigate protein kinase C (PKC) functions on lipopolysaccha ride (LPS)-induced hepatotoxicity, a new potent PKC inhibitor Ro 31-82 20 (Re) was used to detect its effect on LPS-induced hepatotoxicity in rat hepatocytes and tumor necrosis factor (TNF) release from rat Kupf fer cells (KC), METHODS: Hepatocytes (containing KC) were incubated wi th LPS (10 mg . L(-1)) and Ro (0.1-10 mu mol . L(-1)) for 24 h, alanin e aminotransferase (AlaA) leakage in the culture as indication of hepa totoxicity. The TNF activity in the supernatant of rat KC culture with LPS in the presence of Ro (0.1-10 mu mol . L(-1)) was monitored by th e L929 target cell lytic assay, RESULTS: Ro (0.1-10 mu mol . L(-1)) re duced AlaA leakage in the hepatocyte culture, Ro inhibited dose-depend ently the LPS-induced TNF production from rat KC. CONCLUSION: PKC inhi bitor Ro protects the hepatocytes from LPS induced cytotoxicity and in hibits the LPS-induced TNF production from rat KC.