Author/Authors :
ELBERRY, AHMED Beni Suef University - Faculty of Medicine - Department of Pharmacology, Egypt , WAGIH, MOHAMED Beni Suef University - Faculty of Medicine - Department of Pathology, Egypt , ZAHRA, AMR Fayoum University - Faculty of Medicine - Department of Biochemistry, Egypt
Abstract :
Background: Cisplatin (CP) is one of the most effective chemotherapeutic agents and plays a major role in the treatment of a variety of human solid tumours. However, the clinical use of CP is frequently limited, because of its renal toxicity and production of reactive oxygen species (ROS) that intensify the cytotoxic effects. The use of antioxidants could effectively counteract such cytotoxic effects of CP. Oxytocin (OT) was previously shown to have antioxidant properties and anti-inflammatory effects in different inflammatory models. Accordingly, the main aim of the present study is to examine the possible protective influence of oxytocin administration in CP-induced nephrotoxicity.Methods: Male Wistar albino rats were classified into 4 groups: Control group, OT only-treated group which received OT twice (500μg/kg; i.p.) 30 minutes and just before saline administration, CP-induced nephrotoxicity group which received a single dose of CP (7.5 mg/kg; i.p.) and treated with saline, and CP + OT group in the same previous doses. After 72 hours of CP administration, rats were sacrificed and blood was withdrawn for determination of urea, creatinine, albumin and lactate dehydrogenase (LDH). Kidneys were dissected out for histopathological examination, and determination of the tissue levels of reduced glutathione (GSH), malondialdehyde (MDA) nitric oxide (NO) and thiobarbituric acid reactive substances (TBARS). Glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and myeloperoxidase (MPO) activities were also assessed. Results: CP showed histopathological damage and significantly increased serum levels of urea, creatinine and LDH as well as levels of TBARS, MDA, NO and MPO in renal tissues. Meanwhile, serum albumin and tissue levels of GSH, GST, SOD, CAT and GPx decreased. Alterations in these biochemical and histopathological indices due to CP were attenuated by OT.Conclusion: Oxytocin exerts a protective effect against cisplatin-induced nephrotoxicity and this protection is partially mediated through its antioxidant activity.
