الفهرس | Only 14 pages are availabe for public view |
Abstract Despite the existence of a large number of antiepileptic drugs more than 30% of patients with epilepsy have inadequate control of seizures, possibly due to the lack of an understanding of the underlying pathology involved in epileptogenesis. Although mitochondrial dysfunction associated with oxidative stress has been suggested as a potential cause of epileptic seizures and therapy resistant form of severe epilepsy, yet the issue is far from settled. Mitochondria are the primary sites of reactive oxygen species (ROS) production making them vulnerable to oxidative stress and damage. Oxidative damage and mitochondrial dysfunction may be related not only to epileptogenesis but has also been shown to be involved in the pathogenesis of atherosclerosis, stroke, and to be closely related to insulin resistance and metabolic syndrome. The involvement of oxidative damage in cardiovascular disorders as well as in epilepsy might explain the increased rate of association between cardiovascular disease and epilepsy. Whether, the increased risk of cardiovascular diseases in epileptic patients is related to the disease itself or to the antiepileptic drugs is unknown. Patients with epilepsy often require lifelong treatment with medications. Some seizures medications such as valproic acid (VPA) may have chronic metabolic effects and may have a negative impact on vascular risk markers. Moreover, though mechanism of liver toxicity elicited by VPA therapy is quite elusive, oxidative stress has also been hypothesized to play a role in its etiology. PTZ kindling is a widely used chronic model of epilepsy which is associated with ROS generation due to increased activity of glutaminergic transmitter. Accordingly, such a model could be suitable for testing the effects of antioxidants such as TMZ on oxidative stress associated with epilepsy and hence its impact on the antiepileptic activity of VPA and on the metabolic and histopathological changes in hippocampal, aortic and hepatic tissues associated with epilepsy and/or VPA. |