Cisplatin (CP) is a chemotherapeutic drug used in treatment of malignancies. However, its clinical utility is limited by nephrotoxicity. The purpose of the present study was to investigate the protective role of grape seed proanthocyanidin extract (GSPE) (100 mg/kg/day) or fish oil (FO) (5 ml/kg/day) against cisplatin induced nephrotoxicity in terms of biochemical parameters, oxidative stress and DNA damage. CP nephrotoxiciy is manifested by increased levels of serum creatinine, urea and uric acid, accompanied by their decrease in urine. Na, K and Ca levels were altered in both serum and urine. In addition, cisplatin caused a decrease in renal GSH, SH-group, SOD, GST, and Na-K-ATPase levels. However the levels of MDA, H2O2 and NO were increased. Also, we assessed the renal genotoxic potential of cisplatin as manifested by an increase in the tail length of DNA, tail intensity (DNA %) and tail moment. On the other hand, administration of GSPE or FO pre-cisplatin treatment ameliorated the current changes in most of the above tested parameters, particularly oxidative stress, endogenous antioxidant defense system and DNA damage indicating their curative effect. Thus, it can be concluded that the consumption of GSPE or FO might be useful for preventing nephrotoxicity caused by cisplatin treatment.
Cisplatin is an effective chemotherapeutic agent that displays dose-limiting nephrotoxicity. In the present study, the efficacy of grape seed proanthocyanidin extract (GSPE: 100 mg/kg/day) and fish oil (FO: 5 mL/kg/day) against cisplatin-induced nephrotoxicity was evaluated in terms of DNA damage, histopathological changes and expression levels of molecular markers of apoptosis. The administration of cisplatin (CP) (7 mg/kg) results in an increasing percentage of S-phase, G2/M and apoptosis. Furthermore, CP induces apoptosis as indicated by an elevation of renal caspase-3 and reduction in the expression of BCL-2. In addition to occurred renal histopathological changes as manifested by tubular degeneration, degenerative glomerulus, necrotic tubular cells, and cell debris. On the other hand, the administration of GSPE or FO precisplatin treatment can be ameliorated the current DNA cell cycle alterations by the restoration of expression of proteins related to apoptosis and reduced the undesirable renal histopathological changes. So, it can be concluded that the consumption of GSPE or FO might be useful for minimizing nephrotoxicity caused by cisplatin chemotherapy through their anti-apoptotic and antioxidant properties.
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