Lipid Peroxidation and Glutathione Peroxidase, Glutathione Reductase, Superoxide Dismutase, Catalase, and Glucose‐6‐Phosphate Dehydrogenase Activities in FeCl₃‐Induced Epileptogenic Foci in the Rat Brain

Abstract

This study investigated the relationship between lipid peroxidation, subsequent activation of antioxidative enzymes, and development of iron-induced epilepsy in the rat. Epileptic foci were produced in rat cerebral cortex by intracortical injection of ferric chloride (FeCl3). The epileptic foci were identified by electrocorticography (ECoG). Epileptiform ECoG activity was shown to occur in the contralateral homotopic cerebral cortex as well. We measured levels of lipid peroxides and changes in the activities of the enzymes: superoxide dismutase (SOD), glutathione peroxidase (GP), glutathione reductase (GR), catalase (CA), and glucose-6-phosphate dehydrogenase (G6P) in the epileptogenic focus (both ipsilateral and contralateral) at days 3, 8, 15, and 23 after FeCl3 injection. Biochemical estimations were made in subcellular fractions, and changes in the ipsilateral site were compared with those in the contralateral site. The results of this study showed that large increases in lipid peroxidation were associated with development and buildup of the ECoG epileptiform discharges. Lipid peroxides increased in the ipsilateral focus by approximately 100% as compared with control. In the contralateral site, however, the increase in lipid peroxides was marginal only. The increase in lipid peroxidation was concomitant with development of the high level of epileptiform activity. The time course of changes in lipid peroxidation paralleled the time course of development and persistence of the epileptiform activity. Regarding changes in the enzyme activities accompanying development of iron epilepsy, the data showed that although SOD and G6P increased by approximately 60% and GR increased by approximately 40%, the increases in the enzyme GP and CA were much lower, less than 20%. Thus, comparatively less increase in CA and GP activities produces a deficiency of these two enzymes in the iron (ipsilateral) focus. Among the various biochemical disturbances that have been identified as involved in epileptogenesis, peroxidative injury resulting from lipid peroxidation in neural plasma membrane may be causally related to development of paroxysmal epileptiform activity in the iron focus. Since GP is an enzyme of major importance in detoxification of lipid peroxides in the brain, based on the results presented in this article, it appears reasonable to suggest that GP deficiency causes lipid peroxidation to increase tremendously during iron epileptogenesis.

The relationship between excitotoxicity and oxidative stress in the central nervous system

“…60 • 61 Alterations in antioxidant enzyme activities follow chemical-induced seizures. 62 We have found that a brief (1 sec) electroconvulsive shock is sufficient to cause elevated rates of ROS formation in rat cerebral cortex (unpublished data).…”

Effects of endogenous sulfur dioxide on monocrotaline-induced pulmonary hypertension in rats1

“…It has also been reported that oxidative stress may in part contribute to the pathogenesis of PH in a MCT model [33,34] . The antioxidative defense is largely provided by several enzymes such as SOD, GSH-Px, and CAT [35][36][37] . Meng and coworkers [25] indicated that low doses of SO 2 (22 and 56 mg/m 3 ) caused significant increases in SOD, GSH-Px, and CAT activities in the lungs.…”

Ascorbate attenuates trimethyltin-induced oxidative burden and neuronal degeneration in the rat hippocampus by maintaining glutathione homeostasis

“…Abnormalities in glutathione synthesis can result in neurological disorders (Bains and Shaw, 1997;Schweizer et al, 2004), and recent studies have suggested that membrane lipid peroxidation may be involved in epileptogenesis in some experimental models of epilepsy (Kim et al, 1997(Kim et al, , 2000c(Kim et al, , 2002aSingh and Pathak, 1990;Willmore et al, 1986). The production of epileptiform discharges in some forms of experimental epilepsy/convulsion is believed to be mediated by membrane lipid peroxidation initiated by the action of oxygen radicals, which can alter electrophysiologic properties of membranes, such as iongating (Pellmar, 1986).…”