15Nov 2019


  • Department of Human Anatomy, College of Medicine, Taif University, Taif, Saudi Arabia
  • Department of Internal Medicine, College of Medicine, Taif University, Taif, Saudi Arabia
Crossref Cited-by Linking logo
  • Abstract
  • Keywords
  • References
  • Cite This Article as
  • Corresponding Author

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

  1. Abdel Moneim AE (2016) Indigofera oblongifolia Prevents Lead Acetate-Induced Hepatotoxicity, Oxidative Stress, Fibrosis and Apoptosis in Rats PloS one 11:e0158965 doi:10.1371/journal.pone.0158965
  2. Aebi H (1984) [13] Catalase in vitro. In: Methods in Enzymology, vol 105. Academic Press, pp 121-126. doi:https://doi.org/10.1016/S0076-6879(84)05016-3
  3. Aktas A, Nergız Y, Akkus M, Nasır Y (2010) The effects of valproic acid on renal corpuscle of pregnant rats and protective role of folic acid and vitamin E African Journal of Biotechnology 9
  4. Al-Amoudi WM (2017) Protective effects of fennel oil extract against sodium valproate-induced hepatorenal damage in albino rats Saudi journal of biological sciences 24:915-924 doi:10.1016/j.sjbs.2016.10.021
  5. Al-Brakati A, Kassab R, Lokman M, Elmahallawy E, Amin H, Abdel Moneim A (2019) Role of thymoquinone and ebselen in the prevention of sodium arsenite?induced nephrotoxicity in female rats Human & experimental toxicology 38:482-493
  6. Bancroft JD, Gamble M (2008) Theory and practice of histological techniques. Elsevier health sciences,
  7. Berkovic S, Andermann F, Guberman A, Hipola D, Bladin P (1989) Valproate prevents the recurrence of absence status Neurology 39:1294-1294
  8. Brahmane RI, Wanmali VV, Pathak SS, Salwe KJ (2010) Role of cinnarizine and nifedipine on anticonvulsant effect of sodium valproate and carbamazepine in maximal electroshock and pentylenetetrazole model of seizures in mice Journal of pharmacology & pharmacotherapeutics 1:78
  9. Chaudhary S, Ganjoo P, Raiusddin S, Parvez S (2015) Nephroprotective activities of quercetin with potential relevance to oxidative stress induced by valproic acid Protoplasma 252:209-217
  10. Christensen J, Gr?nborg TK, S?rensen MJ, Schendel D, Parner ET, Pedersen LH, Vestergaard M (2013) Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism Jama 309:1696-1703
  11. de la Microvasculatura A et al. (2019) The Alterations of Microvasculature, Tyrosine Phosphorylation, and Lipid Peroxidation in Kidney of Rats Treated with Valproic Acid Int J Morphol 37:65-70
  12. El-Demerdash FM, Yousef MI, Radwan FM (2009) Ameliorating effect of curcumin on sodium arsenite-induced oxidative damage and lipid peroxidation in different rat organs Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 47:249-254 doi:10.1016/j.fct.2008.11.013
  13. El-Mahmoudy A, Matsuyama H, Borgan M, Shimizu Y, El-Sayed M, Minamoto N, Takewaki T (2002) Thymoquinone suppresses expression of inducible nitric oxide synthase in rat macrophages International immunopharmacology 2:1603-1611
  14. El-Shenawy NS, Hamza RZ (2016) Nephrotoxicity of sodium valproate and protective role of L-cysteine in rats at biochemical and histological levels Journal of basic and clinical physiology and pharmacology 27:497-504
  15. Elmaci I, Altinoz MA (2016) Thymoquinone: An edible redox-active quinone for the pharmacotherapy of neurodegenerative conditions and glial brain tumors. A short review Biomedicine & Pharmacotherapy 83:635-640
  16. Frick TW, Speiser DE, Bimmler D, Largiad?r F (1993) Drug-induced acute pancreatitis: further criticism Digestive Diseases 11:113-132
  17. Fuchs J, Milbradt R (1994) Antioxidant inhibition of skin inflammation induced by reactive oxidants: evaluation of the redox couple dihydrolipoate/lipoate Skin Pharmacology and Physiology 7:278-284
  18. Gad AM (2018a) Study on the influence of caffeic acid against sodium valproate-induced nephrotoxicity in rats Journal of biochemical and molecular toxicology 32:e22175 doi:10.1002/jbt.22175
  19. Gad AM (2018b) Study on the influence of caffeic acid against sodium valproate?induced nephrotoxicity in rats Journal of biochemical and molecular toxicology 32:e22175
  20. Gadea J, Sell?s E, Marco MA, Coy P, Mat?s C, Romar R, Ruiz S (2004) Decrease in glutathione content in boar sperm after cryopreservation: Effect of the addition of reduced glutathione to the freezing and thawing extenders Theriogenology 62:690-701
  21. Galaly SR, Abdella EM, Mohammed HM (2014) Effects of royal jelly on genotoxicity and nephrotoxicity induced by valproic acid in albino mice Beni-Suef University Journal of Basic and Applied Sciences 3:1-15
  22. Gholamnezhad Z, Havakhah S, Boskabady MH (2016) Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review Journal of ethnopharmacology 190:372-386
  23. Ghorbani S, Tiraihi T, Soleimani M (2018) Differentiation of mesenchymal stem cells into neuron-like cells using composite 3D scaffold combined with valproic acid induction Journal of biomaterials applications 32:702-715 doi:10.1177/0885328217741903
  24. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids Analytical biochemistry 126:131-138 doi:10.1016/0003-2697(82)90118-x
  25. Inci M et al. (2013) Anti-inflammatory and antioxidant activity of thymoquinone in a rat model of acute bacterial prostatitis Human & experimental toxicology 32:354-361
  26. Janero DR (1990) Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury Free radical biology & medicine 9:515-540 doi:10.1016/0891-5849(90)90131-2
  27. Jones DP (2010) Redox sensing: orthogonal control in cell cycle and apoptosis signalling Journal of internal medicine 268:432-448
  28. Kanner AM (2016) Management of psychiatric and neurological comorbidities in epilepsy Nature Reviews Neurology 12:106
  29. Khan SA (2015) Epilepsy awareness in Saudi Arabia Neurosciences 20:205
  30. Kramer OH et al. (2003) The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2 The EMBO journal 22:3411-3420 doi:10.1093/emboj/cdg315
  31. Kumar O, Sugendran K, Vijayaraghavan R (2003) Oxidative stress associated hepatic and renal toxicity induced by ricin in mice Toxicon 41:333-338
  32. Maneenin MC et al. (2019) The Alterations of Microvasculature, Tyrosine Phosphorylation, and Lipid Peroxidation in Kidney of Rats Treated with Valproic Acid Alteraciones de la Microvasculatura, Fosforilaci?n de Tirosina y Peroxidaci?n Lip?dica en Ri?ones de Ratas Tratadas con ?cido Valproico International Journal of Morphology 37:65-70 doi:10.4067/S0717-95022019000100065
  33. Nwidu L, Ibor O (2019) EC PHARMACOLOGY AND TOXICOLOGY Subchronic Study of Nauclea latifolia Leaf Extract on Valproic Acid-Induced Toxicity in Liver, Lung and Kidney of Rats
  34. Nwidu L, Oboma Y (2019) Musanga cecropioides (Urticaceae) stem-bark mitigates sodium valproate ?induced pantoxicity derangement in albino rats GSC Biological and Pharmaceutical Sciences 7:006-027 doi:10.30574/gscbps.2019.7.1.0050
  35. Silva M et al. (2008) Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: a review Journal of inherited metabolic disease 31:205-216
  36. Srinivasan R, Ratiney H, Hammond-Rosenbluth KE, Pelletier D, Nelson SJ (2010) MR spectroscopic imaging of glutathione in the white and gray matter at 7 T with an application to multiple sclerosis Magnetic resonance imaging 28:163-170
  37. Taka E et al. (2015) Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells Journal of neuroimmunology 286:5-12 doi:10.1016/j.jneuroim.2015.06.011
  38. Zhao YM, Gao LP, Zhang HL, Guo JX, Guo PP (2014) Grape seed proanthocyanidin extract prevents DDP-induced testicular toxicity in rats Food & function 5:605-611 doi:10.1039/c3fo60486a.

[Ashraf Y. Al-Brakati and Naif E. Al omairi (2019); THE PROTECTIVE EFFECTS OF THYMOQUINONE AGAINST VALPROATE - INDUCED NEPHROTOXICITY IN RATS Int. J. of Adv. Res. 7 (Nov). 83-90] (ISSN 2320-5407). www.journalijar.com

Ashraf Y. Al-Brakati
Department of Human Anatomy, College of Medicine, Taif University, Taif, Saudi Arabia


Article DOI: 10.21474/IJAR01/9978       DOI URL: http://dx.doi.org/10.21474/IJAR01/9978

Share this article