Piroxicam Protects against Pentylenetetrazole Kindling: Role of Oxidative Stress and Inflammatory Pathways

Abstract

Increasing evidence has implicated reactive oxygen species and proinflammatory cytokines in incidence of seizures. Hence, this study investigated piroxicam (PXM), a non‐selective cyclooxygenase inhibitor in a pentylenetetrazole (PTZ) kindling model of epilepsy. To this end, male albino rats received a subconvulsive dose of PTZ (35 mg/kg IP on alternate days) for 20 days. Animals were pretreated with PXM (2 mg/kg IP) versus the standard antiepileptic drug valproate (200 mg/kg IP). Kindled rats showed elevation of hippocampal thiobarbituric acid reactive substances (TBARS) and tumor necrosis factor (TNF)‐ α versus a sharp decline in reduced non protein thiols (NPSH). Moreover, PTZ increased the expression of inducible nitric oxide (iNOS) which in turn exacerbates cellular damage. It has been demonstrated that PXM protected against PTZ‐induced seizures and delayed seizure latency onset. PXM reverted the downregulation of NPSH while unpredictably accentuating TBARS above control level. Moreover, PXM inhibited expression of iNOS consequently to the inhibition of TNF‐α thus limiting cellular damage induced by the latter. The results in the present study point that while an increase in proinflammatory cytokines is associated with a pro‐epileptogenic potential, PXM with its antiinflammatory effect showed remarkable anticonvulsive potential and cell protective properties.