Oxytocin ameliorates cisplatin-induced nephrotoxicity in Wistar rats.

BACKGROUND AND OBJECTIVES: The clinical use of cisplatin (CP) is highly limited because of its renal toxicity and the production of reactive oxygen species (ROS) that intensify the cytotoxic effects. Oxytocin (OT) was previously shown to have antioxidant activity. DESIGN AND SETTING: Experimental study on male Wistar albino rats performed in the Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia. METHODS: Forty-eight male Wistar albino rats were classified into four equal groups: a control group, OT only-treated group which received OT twice (500 micro g/kg intraperitoneally (ip) 30 minutes and just before saline administration), a CP-induced nephrotoxicity group that received a single dose of CP (7.5 mg/kg ip) and treated with saline, and CP+OT group treated with the same previous doses. Seventy-two hours after CP administration, the rats were sacrificed and blood was withdrawn for determination of urea, creatinine, albumin and lactate dehydrogenase (LDH). The kidneys were extracted for histopathological examination and determination of the tissue levels of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and nitric oxide end product nitrite (NO(2)). Glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and myeloperoxidase (MPO) activities were assessed. RESULTS: CP-induced renal injury was evidenced histopathologically and manifested by a significant increase in serum LDH activity as well as urea and creatinine levels. Moreover, renal injury was associated with decreased renal tissue activities of CAT, SOD, GPx and GST as well as GSH level. On the other hand, renal tissue content of TBARS and NO(2) as well as the activity of MPO were increased. Alterations in these biochemical and histopathological indices due to CP were attenuated by OT. CONCLUSION: OT protected rats from CP-induced nephrotoxicity. Such protection is attributed, at least in part, to its antioxidant activity.

Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice.

The nephroprotective effect of coenzyme Q10 was investigated in mice with acute renal injury induced by a single i.p. injection of cisplatin (5 mg/kg). Coenzyme Q10 treatment (10 mg/kg/day, i.p.) was applied for 6 consecutive days, starting 1 day before cisplatin administration. Coenzyme Q10 significantly reduced blood urea nitrogen and serum creatinine levels which were increased by cisplatin. Coenzyme Q10 significantly compensated deficits in the antioxidant defense mechanisms (reduced glutathione level and superoxide dismutase activity), suppressed lipid peroxidation, decreased the elevations of tumor necrosis factor-alpha, nitric oxide and platinum ion concentration, and attenuated the reductions of selenium and zinc ions in renal tissue resulted from cisplatin administration. Also, histopathological renal tissue damage mediated by cisplatin was ameliorated by coenzyme Q10 treatment. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the cisplatin-induced overexpression of inducible nitric oxide synthase, nuclear factor-kappaB, caspase-3 and p53 in renal tissue. It was concluded that coenzyme Q10 represents a potential therapeutic option to protect against acute cisplatin nephrotoxicity commonly encountered in clinical practice.