study of the possible neuroprotective effects of an iron chelator and antioxidantin an experimentally induced neurodegenerative lesion in rats

ABSTRACT

Many neurodegenerative diseases have proved to be precipitated not only by age but also by the accumulation of excessive iron content in the basal ganglia which initiates free radical formation. An experimental neurodegenerative lesion was induced in the rat corpus striatum, which is part of the basal ganglia, by intracerebroventricular injection [I.C.V.] of ferric chloride [FeCI3] in a dose of 50mg/5 ml saline for a week. The neuroprotective effect was tested for deferroxamine in a dose of 50mg/kg b.w., intraperitoneally for a week and for vitamin E in a dose of 100mg/kg b.w.,orally for a week. Brain sections of the corpus striatum were studied histologically and histochemically by DOPA [deoxyphenylalanine] reaction. The biochemical parameters for lipid peroxidation by malondialdehyde [MDA], for the natural oxygen scavengers superoxide dismutase [SOD] and reduced glutathione [GSH] and total brain proteins were assessed in blood samples and in brain tissue homogenates. These results were further statistically evaluated. The histological results revealed degenerative changes in the neurons of the corpus striatum of the FeCI3- treated groups with much reduction in the number of dopa positive cells. The lesion showed more improvement on vitamin E administration rather than with deferroxamine therapy. FeCI3 injury induced a rise of brain and blood MDA and SOD, decrease of total brain tissue proteins and reduction of blood GSH. The values of these parameters returned to control values notably more with vitamin E protection rather than with deferroxamine. Accordingly, natural dietary antioxidants were more recommended as neuroprotective and long term therapeutic agents for neurodegenerative diseases than the iron chelating agents