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Protection of epidermal growth factor against clivorine-induced mitochondrial-mediated apoptosis in hepatocytes.
- Source :
-
Environmental toxicology [Environ Toxicol] 2010 Jun; Vol. 25 (3), pp. 304-9. - Publication Year :
- 2010
-
Abstract
- 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.<br /> ((c) 2009 Wiley Periodicals, Inc.)
- Subjects :
- Blotting, Western
Caspase 3 metabolism
Caspase 9 metabolism
Cell Line
Cell Survival drug effects
Cytochromes c metabolism
DNA Fragmentation drug effects
Electrophoresis, Polyacrylamide Gel
Hepatocytes pathology
Humans
Mitochondria, Liver pathology
bcl-X Protein metabolism
Apoptosis drug effects
Epidermal Growth Factor pharmacology
Hepatocytes drug effects
Mitochondria, Liver drug effects
Protective Agents pharmacology
Pyrrolizidine Alkaloids toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1522-7278
- Volume :
- 25
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Environmental toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 19437449
- Full Text :
- https://doi.org/10.1002/tox.20500