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Sci. Pharm. 2006, 74(4), 159-173; doi:10.3797/scipharm.2006.74.159 (registering DOI)

Beneficial Interaction of Thymoquinone and Sodium Valproate in Experimental Models of Epilepsy: Reduction in Hepatotoxicity of Valproate

1
Department of Pharmacology and Therapeutics, College of Medicine, Qassim University, Buraydah, Qassim – Saudi Arabia
2
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
*
Author to whom correspondence should be addressed.
Received: 1 February 2006 / Accepted: 2 September 2006 / Published: 30 December 2006
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Abstract

The antiepileptic potential of thymoquinone (TQ) was studied in mice by using pentylenetetrazole (PTZ) and maximal electroshock seizure (MES)-induced convulsion models. In this investigation, the combined treatment of TQ and sodium valproate (SVP) was also studied. The aim of this part was to minimize SVPinduced hepatotoxic implications, by reducing its antiepileptic dose. TQ in both PTZ- and MES- models increased SVP potency. The experiments dealing with the effects of TQ on the ED50 of SVP revealed that TQ reduced the ED50 of SVP in both the models. However, this potentiation of SVP antiepileptic response was relatively more significant in PTZ model at both 50 and 100 mg/kg doses of TQ. Although very well tolerated and effective, SVP is well known for its hapatotoxic implications. In the experiment dealing with subacute treatment, SVP (1300-1500mg/kg/day in drinking water) for 21 days, produced hepatotoxicity in mice, characterized by elevated serum ALT and AST, reduced levels of non protein sulfhydryls and increase in lipid peroxidation in hepatic cells. Hepato-protection was successfully achieved when TQ (5-5.5mg/kg/day) was combined with SVP in drinking water for the same duration. The protective activity of TQ was evident by averting any serum ALT rise seen in SVP treatment. Though there is no prevention to the rise in lipid peroxidation in hepatic tissue but the same time a significant recovery in glutathione was evident by TQ joint treatment. However, a combination of TQ and low dose of SVP may be useful strategy to minimize adverse reactions of SVP. From the results of the present study that disclosed a protective role of TQ against SVP toxic damage to the liver, it could be mentioned safely that TQ behaves as an antioxidant and protected liver against its harmful effects. It also protected against the liver enzyme induction seen in the case of SVP alone.
Keywords: Thymoquinone; valproate; potentiation; maximal electroshock convulsions; hepatoprotection Thymoquinone; valproate; potentiation; maximal electroshock convulsions; hepatoprotection
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Raza, M.; Alghasham, A.A.; Alorainy, M.S.; El-Hadiyah, T.M. Beneficial Interaction of Thymoquinone and Sodium Valproate in Experimental Models of Epilepsy: Reduction in Hepatotoxicity of Valproate. Sci. Pharm. 2006, 74, 159-173.

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