epidermal-growth-factor and clivorine

Pyrrolizidine alkaloids (PAs) are well-known natural hepatotoxins. In this study, we investigated the protection of epidermal growth factor (EGF) against the hepatotoxicity of clivorine, which is an otonecine-type PA from traditional Chinese medicine Ligularia hodgsonii Hook. Cell viability assay and cell morphology observation showed that EGF (1 ng/mL) reversed clivorine-induced cytotoxicity on human normal liver L-02 cells. EGF (1 ng/mL) also inhibited clivorine-induced DNA fragmentation and caspase-3 cleavage. Our previous study has showed that antiapoptotic Bcl-xL degradation and mitochondrial-mediated apoptosis was involved in clivorine-induced hepatotoxicity. In this study, we found that EGF (1 ng/mL) inhibited clivorine-induced antiapoptotic Bcl-xL protein decrease, caspase-9 activation, and release of cytosolic cytochrome C. We further investigated the effects of vascular epidermal growth factor, basic fibroblast growth factor, and insulin-like growth factor-1 on clivorine-induced cytotoxicity, and there is no significant protection observed. Our results suggest that EGF exerts its protective effects against clivorine-induced hepatotoxicity probably by modulating mitochondrial-mediated apoptotic signal pathway.

Topics: Apoptosis; bcl-X Protein; Blotting, Western; Caspase 3; Caspase 9; Cell Line; Cell Survival; Cytochromes c; DNA Fragmentation; Electrophoresis, Polyacrylamide Gel; Epidermal Growth Factor; Hepatocytes; Humans; Mitochondria, Liver; Protective Agents; Pyrrolizidine Alkaloids