Dose- and Time-dependent Effects of Permethrin on HepG2 Cells: Cell Survival, Lipid Peroxidation and Antioxidant Defence System

Abstract

There is very limited knowledge about in vitro hepatotoxicity of permethrin concerning dose and duration even though humans and nontargeted beings are exposed. In this study, three different doses of permethrin (1 mu M, 10 mu M, 100 mu M) were administered in three different time periods (24, 48, 72 h) and cell viability (WST-1 and Trypan blue test), lipid peroxidation (high performance lipid chromatography), and antioxidant (SOD-1, SOD-2 and GPx-1) gene expression levels (real time PCR) were evaluated. The LC50 dose of permethrin was calculated as 1111 mu M. Significant decrease in cell viability was detected in every time period except at the lowest dose (P<0.05). Each permethrin dose caused a significant increase (P<0.01) in superoxide dismutase-1 levels (except 1 tiM at 48 h). The 10 mu M and 100 mu NI groups' superoxide dismutase-2 levels were higher than the controls at each exposure level though the 1 mu M group was significantly lower at 24 and 48 h and higher at 72 h. Interestingly, a non-uniform statistically significant difference for glutathione peroxidase-1 was seen in each exposure duration and doses either as up- or down regulation (P<0.01). Generally, malondialdehyde concentrations were significantly increased (P<0.01), although at each dose in 72 h a significant decrease in malonaldehyde levels was seen (P<0.01). Our results may help in understanding the molecular aspects of high dose permethrin hepatotoxicity. More comprehensive research is required to evaluate long term low dose exposure.