Anticonvulsant activity of oxaprozin in a rat model of pentylenetetrazole-induced seizure by targeting oxidative stress and SIRT1/PGC1α signaling

Abstract

The effect of oxaprozin (OXP) on experimental model of seizures in rats is investigated in the present study. Seizures in Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg). The anticonvulsant effect of OXP (100, 200 and 400 mg/kg, intraperitoneally) is evaluated in seizure model. After behavioral tests, the animals underwent deep anesthesia and were put down painlessly. Animal serum was isolated for antioxidant assays (NO, and GSH). The animals' brains were also isolated to gauge the relative expression of genes in the oxidative stress pathway (Sirt1 and Pgc1α). Intraperitoneal injection of OXP increased the mean latency of myoclonic jerks and generalized tonic-clonic seizure (GTCS) and decreased the number of myoclonic jerks and GTCS duration compared to the PTZ group. Biochemical tests showed that pretreatment with OXP was able to restore GSH serum levels and reverse the augmented NO serum levels caused by PTZ induction to normal level. The qPCR results also unveiled that OXP counteracts the negative effects of PTZ by affecting the expression of Sirt1 and Pgc1α genes. Overall, this study suggests the potential neuroprotective effects of the nonsteroidal, anti-inflammatory OXP drug in a model of neural impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.

Drug repositioning for idiopathic epilepsy using gene expression signature data

“…Non steroidal anti-inflammatory drug (NSAIDs) oxaprozinis also reported to have an anti-epileptic effect in rat models [ 38 , 39 ]. But the other predicted NSAIDs, ketoprofen, do not show any anti-epileptic response during in-vivo studies [ 40 ].…”