Enantioselective induction of oxidative stress by permethrin in rat adrenal pheochromocytoma (PC12) cells

Abstract

Synthetic pyrethroid (SP) insecticides are chiral compounds with multiple asymmetric positions. Several recent studies have focused on the effect of enantioselectivity of SPs in acute aquatic toxicity, endocrine-disrupting activities, and immunotoxicity. However, the relevant molecular mechanisms are still unknown. The potential relationship between ecotoxicological effects and oxidative stress could contribute to SP-induced enantioselective cytotoxicity, but this requires further investigation. Therefore, this study was undertaken to evaluate the role of oxidative stress in enantiomer-specific permethrin (PM)-induced cytotoxicity in rat adrenal pheochromocytoma (PC12) cells. The study demonstrated that PM induced enantioselective oxidative stress and cytotoxicity. The reactive oxygen species (ROS) generation and lipid peroxidation production of malondialdehyde (MDA) were obviously increased, whereas the activity of antioxidant enzymes (superoxide dismutase [SOD] and catalase [CAT]) and glutathione (GSH) content had declined after exposure in 1R-trans-PM at a concentration of 30 mg/L. Meanwhile, the result of the cytotoxicity assay showed a clear, dose-dependent growth-inhibition effect of PM in an enantioselective manner. The most toxic effect on PC12 cells was shown by 1R-trans-PM and was approximately 1.6 times higher than that with 1S-cis-PM, which exhibited only a slightly toxic effect at a concentration of 20 mg/L. These results suggested that PM exhibited significant enantioselectivity in oxidative stress, which may be one of the initial events in PM-induced enantioselective cytotoxicity. The present study also improved understanding of enantiomer-specific, SP-induced cytotoxicity. The enantioselectivity should be taken into consideration when assessing ecological effects and development of new chiral pesticides.