Chemical Identity of Interaction of Protein with Reactive Metabolite of Diosbulbin B In Vitro and In Vivo.

ABSTRACT: Diosbulbin B (DIOB), a hepatotoxic furan-containing compound, is a primary ingredient in Dioscorea bulbifera L., a common herbal medicine. Metabolic activation is required for DIOB-induced liver injury. Protein covalent binding of an electrophilic reactive intermediate of DIOB is considered to be one of the key mechanisms of cytotoxicity. A bromine-based analytical technique was developed to characterize the chemical identity of interaction of protein with reactive intermediate of DIOB. Cysteine (Cys) and lysine (Lys) residues were found to react with the reactive intermediate to form three types of protein modification, including Cys adduction, Schiff's base, and Cys/Lys crosslink. The crosslink showed time- and dose-dependence in animals given DIOB. Ketoconazole pretreatment decreased th

SUBMITTER: Wang K 

PROVIDER: S-EPMC5577583 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature