Alleviation of Oxidative Damage and Involvement of Nrf2-ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline.

Yunxiao Kang,Yakun Du,Huixian Cui,Lei Wang,Hui Fang,Geming Shi,Guoliang Zhang,Wensheng Yan

doi:10.1155/2017/7908072

Yunxiao Kang, Yakun Du + Show 6 more

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https://doi.org/10.1155/2017/7908072

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Abstract

The current studies were aimed at evaluating the efficacy of intranasal pentoxifylline (Ptx) pretreatment in protecting mesodopaminergic system and hippocampus from oxidative damage of lithium-pilocarpine induced status epilepticus (SE) and the involvement of nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response elements pathway. Pentoxifylline was administered to rats intranasally or intraperitoneally 30 minutes before inducing SE. Our results showed the impaired visuospatial memory, the defected mesodopaminergic system, and the oxidative damage and the transient activation of Nrf2 in SE rats. The transient activation of Nrf2 in SE rats was enhanced by Ptx pretreatment, which was followed by the upregulation of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Ptx pretreatment to SE rats significantly suppressed the epileptic seizures, decreased the levels of lipid peroxide and malondialdehyde, and elevated the ratio of reduced glutathione/oxidized glutathione. Compared with intraperitoneal injection, intranasal Ptx delivery completely restored the visuospatial memory and the activity of mesodopaminergic system in SE rats. Intranasal administration of Ptx may hopefully become a noninvasive, painless, and easily administered option for epileptic patients.

Highlights

Epilepsy is a life-threatening medical emergency that warrants immediate treatment to prevent seizure activity and associated neuronal damage [1]
All the rats in Status epilepticus (SE)-cl developed into epileptic seizures and into SE after the injection of Pc. 10% of them died over a period of 24 hrs
The present studies revealed that the epileptic seizures, the impaired visuospatial memory, and the defected mesodopaminergic system in SE rats induced by Li-Pc were effectively ameliorated by pretreatment of Ptx via intranasal delivery, as well as via intraperitoneal injection

Summary

Introduction

Epilepsy is a life-threatening medical emergency that warrants immediate treatment to prevent seizure activity and associated neuronal damage [1]. Intramuscular or intravenous injection cannot be implemented immediately outside of hospital settings, delaying or missing the best treatment time and threatening the human life. The intranasal route to administer drugs is quick and effective in targeting the brain [4, 5] and potentially provides a direct delivery of the drug to the central nervous system [6, 7] bypassing the blood-brain barrier and exerting therapeutic effects at terminating epileptic seizures. Intranasal drug administration is noninvasive, painless, and administered for epileptic patients [4] in the home treatment of prolonged seizures and in the treatment of prehospital seizures by emergency medical technicians [8]

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