The effects of quinacrine, proglumide, and pentoxifylline on seizure activity, cognitive deficit, and oxidative stress in rat lithium-pilocarpine model of status epilepticus.

Mohammad Ahmad,Gasem M Abu-Taweel,Jamaan S Ajarem,Ahmad E Aboshaiqah

doi:10.1155/2014/630509

Abstract

The present data indicate that status epilepticus (SE) induced in adult rats is associated with cognitive dysfunctions and cerebral oxidative stress (OS). This has been demonstrated using lithium-pilocarpine (Li-Pc) model of SE. OS occurring in hippocampus and striatum of mature brain following SE is apparently due to both the increased free radicals production and the limited antioxidant defense. Pronounced alterations were noticed in the enzymatic, glutathione-S transferase (GST), catalase (CAT), and superoxide dismutase (SOD), as well as in the nonenzymatic; thiobarbituric acid (TBARS) and reduced glutathione (GST), indices of OS in the hippocampus and striatum of SE induced animals. Quinacrine (Qcn), proglumide (Pgm), and pentoxifylline (Ptx) administered to animals before inducing SE, were significantly effective in ameliorating the seizure activities, cognitive dysfunctions, and cerebral OS. The findings suggest that all the drugs were effective in the order of Ptx < Pgm < Qcn indicating that these drugs are potentially antiepileptic as well as antioxidant; however, further studies are needed to establish this fact. It can be assumed that these antiepileptic substances with antioxidant properties combined with conventional therapies might provide a beneficial effect in treatment of epilepsy through ameliorating the cerebral OS.

Highlights

Status epilepticus (SE) is an emergency neurological condition where recurrent generalized seizures last for more than 30 minutes and if not controlled neuronal injury occurs [1, 2]
The convulsive episode consisted of head bobbing with intermittent forelimb and hind limb clonus, hyperextension of tails, loss of posture, falling back, and myoclonic jerks building up to SE in 100% of animals
A total of 10% mortality were observed over a period of 24 h following Pc injections (Table 1)

Summary

Introduction

Status epilepticus (SE) is an emergency neurological condition where recurrent generalized seizures last for more than 30 minutes and if not controlled neuronal injury occurs [1, 2]. SE is preferentially associated with a wide range of neurochemical imbalance in some areas of the brain [3,4,5,6]. Such neuronal hyperactivity and/or excitotoxicity have been associated with excessive generation of free radicals [7, 8], in the brain, which contains large quantities of oxidizable lipids and metals, and the brain has fewer mechanisms of antioxidation than other tissues [9]. The pathological process and underlying mechanisms involved in the oxidative stress during SE are still

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