Genetic overexpressing of GPx-1 attenuates cocaine-induced renal toxicity via induction of anti-apoptotic factors

The present study investigates the role of the glutathione peroxidase (GPx)-1 gene in cocaine-induced renal damage in mice. Multiple doses of cocaine increased lipid peroxidation, protein oxidation, and glutathione oxidation in the kidney of the non-transgenic mice (non-TG mice). The enzymatic activities of GPx and glutathione reductase were significantly decreased in non-TG mice, whereas superoxide dismutase was increased in the early phase of cocaine exposure. Treatment with cocaine resulted in significant decreases in expression of Bcl-2 and Bcl-xl in the kidney of non-TG mice, which resulted in significant increases in Bax and cleaved-caspase 3. Consistently, cocaine-induced tubular epithelial vacuolization and focal tubular necrosis were mainly observed in the proximal tubules in the kidneys of non-TG mice. These renal pathologic changes were much less pronounced in GPx-1 TG than in non-TG mice. These results suggest that the GPx-1 gene is a protective factor against nephrotoxicity induced by cocaine via interactive modulations between antioxidant and cell survival signaling processes.