CALCITONIN PREVENTS CCL4-INDUCED HYDROPEROXIDE GENERATION AND CYTOTOXICITY POSSIBLY THROUGH C1B RECEPTOR IN RAT HEPATOCYTES

The effects of calcitonin (CT) on oxyradical generation and cellular d amage induced by carbon tetrachloride (CCl4) were investigated in rat hepatocytes. Addition of CCl4 to the cells concentration dependently i ncreased intracellular production of hydroperoxides and release of asp artate aminotransferase (AST) and alanine aminotransferase (ALT). The hepatocytes expressed mRNA for a CT receptor, Clb. Coaddition of CT to the cells concentration dependently suppressed the CCl4-induced incre ase in hydroperoxide production and also decreased the release of AST and ALT. The suppressive effect of CT on hydroperoxide production was reversed by further addition of H7 or by pretreatment with phorbol 12- myristate 13-acetate for 24 h. These results suggest that CT prevents CCl4-induced oxyradical production and cellular damage through activat ion of protein kinase C in hepatocytes. (C) 1996 Academic Press, Inc.