RENOPROTECTIVE EFFECTS OF THYMOQUINONE AGAINST CISPLATIN-INDUCED NEPHROTOXICITY IN RATS

Abstract

Background: Cisplatin (CIS) is one of the most effective chemotherapeutic agents and is used to treat various types of tumors. However its optimal clinical benefit is limited by its serious nephrotoxicity. Objective: Investigating the possible effects of thymoquinone (TQ), a compound derived from Nigella sativa with strong anti-oxidant properties, against CIS-induced nephrotoxicity. Materials and Methods: Forty adult male albino rats were divided into four equal groups: Rats in the first group were injected daily with normal saline, rats in the second group received TQ, rats in the third group were injected with CIS on the sixth day of experiment, whereas rats in the fourth group received TQ in drinking water for 11 consecutive days in addition to CIS injection (7.5 mg/kg, i.p.) on the sixth day of experiment. The animal were sacrificed at day 12 and following parameters were evaluated: (i) the levels of serum creatinine (Cr) and the blood urea nitrogen (BUN) as biomarkers of renal function, (ii) the renal content of thiobarbituric acid reactive substances (TBARS) as an index of lipid perioxidation and oxidative stress, (iii) total glutathione (GSH) content and glutathione S-transferase (GST) activity in renal tissues as indices of antioxidant mechanisms, and (iv) the histopathological hallmarks of kidney specimens. Results: CIS administration induced nephrotoxicity associated with significant higher in the levels of serum Cr, BUN, and renal TBARS and significant reductions in the renal GSH and GST. The histopathological findings supported the presence of seriously injured kidney. However, administration of TQ efficiently reduced the development of CIS nephrotoxicity and its associated biochemical and histopathological features. Conclusion: TQ mediates via, at least in part its antioxidant property, a marked renoprotective effect against CIS-induced nephrotoxicity.