Turkish Journal of Nephrology
Original Article

Modulation of Nrf2/HO-1 by Thymoquinone During Cisplatin-Induced Nephrotoxicity

1.

Firat University School of Medicine, Department of Nephrology, Elazig, Turkey

2.

Firat University Faculty of Science, Department of Biology, Elazig, Turkey

3.

Wayne State University School of Medicine, Department of Oncology, Detroit, USA

4.

Firat University Faculty of Veterinary Science, Department of Animal Nutrition, Elazig, Turkey

Turkish J Nephrol 2013; 22: 182-187
DOI: 10.5262/tndt.2013.1002.09
Read: 739 Downloads: 475 Published: 05 February 2019

OBJECTIVE: Side effects of cisplatin, such as nephrotoxicity, limit its use in chemotherapeutic regimens and indicate an agent that suppresses its toxicity. Thymoquinone (TQ), the predominant bioactive constituent present in black seed oil (Nigella sativa), has antiinfl ammatory, antioxidant and antitumor effects. We propose a protective mechanism of of TQ on cisplatin-nephrotoxicity in rats that is through modulation of Nrf2-mediated antioxidant induction and reduced inflammation.

MATERIAL and METHODS: Twenty-eight male Wistar rats (8 weeks-old) were divided into four groups; Control (vehicle; 0.9% saline, 1 ml/kg body wt., p.o.), TQ (10 mg/kg body weight/day in drinking water for 5 days), cisplatin (a single injection of 7mg/kg body wt, i.p.) and TQ for 5 days in drinking water then a single injection of cisplatin. On day 10, all rats were sacrifi ced by cervical dislocation, kidneys were removed, and serum urea and creatinine were collected.

RESULTS: Serum urea and creatinine levels were signifi cantly higher in cisplatin-treated rats compared with control rats. TQ-treatment signifi cantly decreased serum urea and creatinine levels. Cisplatin-treatment caused signifi cant downregulation of the nuclear NF-E2-related factor-2 (Nrf2), heme oxygenase-1(HO-1) and caused an increase in the levels of nuclear factor-kappa B (NF-κB). Interestingly, TQ supplementation signifi cantly improved the changes associated with cisplatin nephrotoxicity by increasing the levels of Nrf-2 and HO-1 and decreasing the levels of NF-κB.

CONCLUSION: This study demonstrates the TQ targets NRF2/HO-1 and can be used as a potential agent against cisplatin-induced nephrotoxicity.

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