Do antioxidant enzymes and glutathione play roles in the induction of hepatic oxidative stress in mice upon subchronic exposure to mixtures of dichloroacetate and trichloroacetate?

Abstract

Dichloroacetate (DCA) and trichloroacetate (TCA) are water chlorination by-products, and their mixtures were previously found to induce additive to greater than additive effects on hepatic oxidative stress (OS) induction in mice after subchronic exposure. To investigate the roles of antioxidant enzymes and glutathione (GSH) in those effects, livers of B6C3F1 mice were treated by gavage with 7.5, 15, or 30 mg DCA/kg/day, 12.5, 25, or 50 mg TCA/kg/day, and mixtures (Mix I, Mix II, and Mix III) at DCA:TCA ratios corresponding to 7.5:12.5, 15:25, and 25:50 mg/kg/day, respectively, for 13 weeks. Livers were assayed for superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), as well as for GSH levels. In general, DCA suppressed SOD and GSH-Px activities and GSH levels but caused no changes in CAT activity; TCA increased SOD and CAT activities, suppressed GSH-Px activity, but did not change GSH levels; mixtures of DCA and TCA increased SOD and CAT activities and suppressed GSH-Px activity and GSH levels. In conclusion, antioxidant enzymes contribute to DCA-, TCA-, and mixtures-induced OS, but not to changes from additive to greater than additive effects produced by different mixture compositions of the compounds. GSH on the other hand may contribute to these changes.

Keywords:

• dichloroacetate
• trichloroacetate
• mixtures
• antioxidant enzymes
• glutathione

Acknowledgments

The project was supported by grant number R15ES013706 from the National Institute of Environmental Health Sciences (NIEHS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIEHS.