Thymoquinone Prevents Valproic Acid-Induced Nephrotoxicity in Rat Kidney

Abstract

Valproic acid (VA), widely used as an antiepileptic, causes structural and functional kidney disorders. Whether thymoquinone (TQ) has a beneficial effect on valproic acid (VA)-induced nephrotoxicity has been investigated. Twenty-one male Spraque Dawley rats were grouped into control, VA, and VA + TQ groups (n=7 for per group). VA (500 mg/kg/day) and TQ (50 mg/kg/day) were applied to the rats orally for 14 days. They were euthanized on the 15th day of the treatment. The cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) gene expression levels, biochemical parameters, total antioxidant/oxidant statuses (TAS/TOS), oxidative stress index (OSI), histological and immunohistochemical analysis were performed to evaluate kidney toxicity. In the VA + TQ group, COX-1 expression levels increased, while COX-2 expression levels decreased. While the creatinine (Cr) and blood urea nitrogen (BUN) levels, production of caspase-3 (CAS-3) and NADPH oxidase-4 (NOX-4) were increased in the VA-treated group, they were decreased in VA + TQ group. Treatment with TQ against VA administration decreased TOS and OSI levels while increasing TAS. TQ protects the kidney against the toxic effects of VA.

Keywords

• Apoptosis
• COX-1
• COX-2
• Oxidative stress
• Thymoquinone
• Valproic acid

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