Elsevier

Neuroscience

Volume 146, Issue 4, 8 June 2007, Pages 1758-1771
Neuroscience

Neuropharmacology
Alpha-lipoic acid differently affects the reserpine-induced oxidative stress in the striatum and prefrontal cortex of rat brain

https://doi.org/10.1016/j.neuroscience.2007.04.002Get rights and content

Abstract

Antioxidative properties of α-lipoic acid (LA) are widely investigated in different in vivo and in vitro models. The aim of this study was to examine whether LA attenuates oxidative stress induced in rats by reserpine, a model substance frequently used to produce Parkinsonism in animals. Male Wistar rats were treated with reserpine (5 mg/kg) and LA (50 mg/kg) separately or in combination. The levels of reduced glutathione (GSH), glutathione disulfide (GSSG), nitric oxide (NO) and S-nitrosothiols as well as activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST) and L-γ-glutamyl transpeptidase (γ-GT) were determined in the striatum and prefrontal cortex homogenates.

In the striatum and prefrontal cortex a single dose of reserpine significantly enhanced levels of GSSG and NO but not that of S-nitrosothiols when compared with control. In the striatum, LA administered jointly with reserpine markedly increased the concentration of GSH and decreased GSSG level. In the prefrontal cortex, such treatment produced only an increasing tendency in GSH level but caused no changes in GSSG content. In both structures LA injected jointly with reserpine markedly decreased NO concentrations but did not cause significant changes in S-nitrosothiol levels when compared with control. Enzymatic activities of GPx and GST were intensified by LA in the striatum. In the prefrontal cortex, GPx activity was not altered, while that of GST was decreased. γ-GT activity was attenuated by reserpine in the striatum while LA reversed this effect. Such changes were not observed in the prefrontal cortex.

The mode of LA action in the striatum during the reserpine-evoked oxidative stress strongly suggests that this compound may be of therapeutic value in the treatment of Parkinson’s disease.

Section snippets

Experimental procedures

All the experiments were carried out according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals (publication no. 85–23, revised 1985) and were approved by the internal Bioethics Commission. All efforts were made to minimize the number of animals used and their suffering.

The effect of acute i.p. administration of LA and reserpine, separately and jointly, on the striatal levels of the total, reduced and oxidized glutathione

The total glutathione (GSH+GSSG) levels in the striatum did not differ significantly between groups of rats treated with LA or reserpine alone. However, the combined administration of both these compounds caused a significant increase in its concentration when compared with the control (by 16.7%) and the reserpine-treated (by 17.1%) groups (Fig. 1A). When the GSH was analyzed, it was found that its level was significantly decreased in the reserpine-treated group (by 14.5% of LA-treated group),

Discussion

The present study demonstrated for the first time that LA affected in a different manner the GSH defense system in the examined dopaminergic structures of rat brain under conditions of the reserpine-induced oxidative stress. The striatum and the prefrontal cortex are brain regions that differ markedly in respect of DA concentrations. The striatum densely innervated by dopaminergic projection arising from the SNc is the richest in DA content brain structure. Contrary to the striatum, the

Conclusion

In conclusion, our results confirm a beneficial effect of LA in alleviating results of oxidative stress associated with the enhanced DA catabolism in the rat striatum. Administration of this drug strengthens the GSH defense system of that structure by increasing both GSH level as well as activities of two important detoxifying enzymes, i.e. GPx and GST. LA protects also TH against loss of its physiological function. It seems that such a mode of action makes LA a useful drug for treatment of PD

Acknowledgments

This work was supported by the Polish Ministry of Education and Sciences, grant no. 2PO5F 010 27.

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