Lindane-Induced Generation of Reactive Oxygen Species and Depletion of Glutathione do not Result in Necrosis in Renal Distal Tubule Cells

Abstract

Lindane is a chlorinated hydrocarbon pesticide, currently used in prescription shampoos and lotions to treat scabies and lice infestations. Lindane is known to be nephrotoxic; however, the mechanism of action is not well understood. In other organ systems, lindane produces cellular damage by generation of free radicals and oxidative stress. Morphological changes were observed in lindane-treated Madin–Darby canine kidney (MDCK) cells indicative of apoptosis. Lindane treatment induced time-dependent reactive oxygen species (ROS) generation. Onset of ROS generation correlated with an initial increase in total glutathione (GSH) levels above control values, with a subsequent decline in a time-dependent manner. This decline may be attributed to quenching of free radicals by GSH, thereby decreasing the cellular stores of this antioxidant. Necrotic injury was assessed by measuring lactate dehydrogenase (LDH) leakage from the cell after lindane exposure. No significant LDH leakage was noted for all concentrations tested over time. Generation of ROS and alterations in cellular protective mechanisms did not result in necrotic injury in MDCK cells, which corresponds with our morphological findings of lindane-induced apoptotic changes as opposed to necrosis in MDCK cells. Thus, lindane exposure results in oxidative damage and alterations in antioxidant response in renal distal tubule cells, followed by cell death not attributed to necrotic injury.

Acknowledgements

This material was previously presented at the 45th annual Society of Toxicology meeting. Funding supported by grant T42 OH008421 from the National Institute for Occupational and Environmental Health (NIOSH)/Centers for Disease Control and Prevention (CDC) to the Southwest Center for Occupational and Environmental Health (SWCOEH), a NIOSH Education and Research Center.