The persistent environmental pollutant chlordane has been implicated as a factor contributing to the epidemic of obesity and diabetes. Major components of technical chlordane (trans-chlordane, cis-chlordane and heptachlor) and their metabolites are chiral. This study investigated the enantioselective metabolism of those chemicals by liver microsomes prepared from rats treated with corn oil (CO) or inducers of CYP2B (PB; Phenobarbital) and CYP3A enzymes (DX; dexamethasone). The extent of the metabolism of all three chemicals was dependent on microsomal preparation used, and followed the rank order PB > DX > CO. Both cis- and trans-chlordane were enantioselectively metabolized to oxychlordane and another, currently unknown metabolite. Heptachlor was metabolized enantioselectively to heptachlor epoxide. Interestingly, the direction on the enrichment for oxychlordane, heptachlor epoxide and the unknown metabolite differed depending on the microsomal preparation. Overall, our results suggest that components of chlordane are enantioselectively metabolized by different cytochrome P450 isoforms.

Chlordane is enantioselectively metabolized by hepatic microsomes

245th National Meeting (2013)

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