Effect of Pravastatin on Levels of Filtration Slit Diaphragm Protein and Oxidative Stress in Doxorubicin- Induced Nephrotoxicity

Abstract:

Introduction: Nephrotoxicity is one of the complications the use of doxorubicin (DXR) which may be caused by the formation of free radicals. The aim of this study was to investigate the effects of pravastatin (PS) on doxorubicin-induced nephrotoxocity. Methods: The rats were divided into control, doxorubicin (15 mg/kg, i.p.), PS (20 mg/kg orally, 5 days prior to DXR injection) + DXR and DXR + PS (5 days after DXR injection) groups. At the end of the 20^th day, kidneys were removed for evaluation. Podocin mRNA and protein were determined by real–time PCR and Western blotting. Also, the level of tissue’s malondialdehyde (MDA), catalase (CAT), Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were determined. Results: Adminstration of pravastatin increased (P < 0.005) the mRNA and protein expression of podocin and the activities of CAT, SOD and GPx which were decreased in doxorubicin group. Pravastatin also, reduced (P < 0.005) the elevated MDA level in doxorubicin group. Conclusion: The present study showed that that pravastatin can improve doxorubicin-induced nephrotoxicity in rats which is associated with the increase in expression of podocin and antioxidant enzymes activities, and decrease in level of MDA.

Key words: Pravastatin, Doxorubicin, Nephrotoxicity, Oxidative stress, Podocin.