THE PROTECTIVE EFFECTS OF THYMOQUINONE AGAINST VALPROATE - INDUCED NEPHROTOXICITY IN RATS

Background: Valproate is commonly used to treat epilepsy seizures. This study was designed to examine the protective role of thymoquinone against nephrotoxicity induced by valproate through estimating the oxidative status, kidney function parameters and histopathological alteration in the kidney of rats. Methods: Forty rats were divided into four groups (n=10): control group; thymoquinone group was administered with thymoquinone (10 mg/kg); the valproate group was orally given 500 mg/kg; and the valproate + thymoquinone group was co-administrated with thymoquinone following valproate for twenty-eight days. Results: Valproate administration impaired the balance between oxidants and antioxidants as evedienced by markedly increase in malondialdehyde (MDA), nitric oxide (NO), nuclear factor kappa-B (NF-kB) coupled with the decrease of glutathione (GSH) and catalase (CAT). Biochemical findings showed a marked increase in the urea and creatinine levels following valproate intoxication. Also, histological examination revealed congested glomerular capillaries with increased cellularity of meningeal cells admixed with congested blood vessels in the interstitial tissue. In contrast, thymoquinone administration ameliorated the histopathological damages and biochemical alterations produced by valproate. Conclusion: These findings suggest that co-administration of thymoquinone following valproate ameliorated the changes in the oxidative damage, inflammation, and histopathological alterations in renal tissues which may be by facilitating valproate biomethylation and excretion