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Furanoterpenoid diosbulbin B (DSB) is a major component responsible for the hepatotoxicity of herbal medicine Dioscorea bulbifera L. (DBL). The metabolic oxidation of the furan moiety of DSB is considered to initiate its liver toxicity. The resulting reactive intermediate reacts with hepatic protein to form protein covalent binding. DSB-derived protein adduction-based biomarker was developed to evaluate DBL exposure. Immunoblot assay indicated the plasma protein of rats treated with DBL extract was covalently modified by the metabolite of DSB. Assessment of DSB-induced protein adduction was achieved by LC-MS/MS analysis of proteolytic digestion of adducted protein. Pyrroline derivatives were detected in proteolytic plasma obtained from rats administered DBL extract. The protein adduction elevated with the increase in the dosage DBL extract. A detectable level of plasma protein adduction was observed 10 days after withdrawal of DBL extract post 30-day continuous administration. In addition, the elevation of serum ALT was found to be proportional to the levels of plasma protein adduction. In conclusion, the DSB-derived plasma protein adduction well correlated with the exposure and hepatotoxicity of DBL. The protein adduction may be used as a good biomarker for diagnosis of DBL-induced liver injury and a useful indicator for DBL medication plans.
Keywords: Dioscorea bulbifera L., Diosbulbin B, Protein adducts, Biomarker, Hepatotoxicity.
