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

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 ED 50 of SVP revealed that TQ reduced the ED 50 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 harmful effects. It also protected against the liver enzyme induction seen in the case of SVP alone. KeywordsThymoquinone, valproate, potentiation, maximal electroshock convulsions, hepatoprotection.Abbreviations: maximal electroshock seizure = MES; pentylenetetrazole = PTZ; thymoquinone = TQ; sodium valproate = SVP; malondialdehyde = MDA; nonprotein sulfhydryl groups = NPSH; glutathione = G-SH.

The protective effect of Nigella Sativa oil extract against neurotoxicity induced by Valproic acid

“…Treatment of VPA with NSO extracts include of TQ (A major component t of volatile oil of Nigella species) is an antioxidant and keeps liver against VPA induced toxic damage. TQ significantly declined the AST and ALT activities (Raza et al, 2006). …”

Methanol extract of Nigella sativa seed induces changes in the levels of neurotransmitter amino acids in male rat brain regions

“…The antiepileptic effects of the main constituents of NS seed have been evaluated using different agents - induced seizures (Hosseinzadeh & Parvardeh 2004 ; Raza et al. 2006 , 2008 ; Ezz et al. 2011 ), and the involvement of GABA receptors in this process has been acknowledged, as well.…”

Therapeutic Potential and Pharmaceutical Development of Thymoquinone: A Multitargeted Molecule of Natural Origin

“…Thus, the alteration of the expression of key proteins such as Bcl-2, Bax, Caspase-9, Caspase-3, and PARP-1 by TQ and Metformin were showed in conferring the therapeutic activities (Ilhan et al, 2005 ; Al-Majed et al, 2006 ). Further, Raza et al ( 2006 ) reported that TQ also diminishes sodium valproate induced hepatotoxicity. TQ synergistically enhances the efficacy of sodium valproate at doses 50 and 100 mg/kg in PTZ as well as MES models.…”