The Role of Oxidative Stress in Enantiomer-Specific, Bifenthrin-Induced Cytotoxicity in PC12 Cells

With the widespread use of synthetic pyrethroids (SPs), the various toxic effects of these compounds have attracted much interest with respect to the investigation of involved mechanisms. However, research on molecular mechanisms of enantioselective toxicity of SPs has been limited. Our previous investigations suggested that enantiomers of cis-bifenthrin (cis-BF) behaved enantioselectively in endocrine disruption and mammalian cytotoxicity. While little is known about the molecular mechanism of the enantioselective toxicity of cis-BF, recent experiments implicated oxidative stress in the cytotoxicity of many SPs. Therefore, the aim of this study was to determine whether cis-BF enantioselectively induced oxidative stress lead to enantioselective cytotoxicity. In this article, we used the rat pheochromocytoma PC12 cell line as an in vitro model to evaluate the involvement of the oxidative stress pathway in enantioselective cytotoxicity of cis-BF. Following exposure of cells to cis-BF and its enantiomers, a significant reduction in cell survival and superoxide dimutase, as well as increased production of lactate dehydrogenase, intracellular reactive oxygen species and malondialdehyde, was observed in 1S-cis-BF, while 1R-cis-BF exhibited these effects to a lesser degree. These results clearly demonstrated that enantiomer-specific cis-BF-induced oxidative damage is possibly an initiating event and contributes, at least in part, to the mechanism of cis-BF-induced enantioselective cytotoxicity. Furthermore, our study also indicated that enantioselectivity should be considered when evaluating the ecotoxicological effects and the health risks of chiral contaminants. (C) 2009 Wiley Periodicals, Inc. Environ Toxicol 26: 271-278, 2011.