Oxidative derangement in rat synaptosomes induced by hyperglycaemia: restorative effect of dehydroepiandrosterone treatment.
Central nervous system damage in diabetes is caused by both cerebral atherosclerosis and the detrimental effect of chronic hyperglycaemia on nervous tissue. Hyperglycaemia is the primer of a series of cascade reactions causing overproduction of free radicals. There is increasing evidence that these reactive molecules contribute to neuronal tissue damage. Dehydroepiandrosterone (DHEA) has been reported to possess antioxidant properties. This study evaluates the oxidative status in the synaptosomal fraction isolated from the brain of streptozotocin-treated rats and the antioxidant effect of DHEA treatment on diabetic rats. Hydroxyl radical generation, hydrogen peroxide content, and the level of the reactive oxygen species was increased (P<0.05) in synaptosomes isolated from streptozotocin-treated rats. The derangement of the oxidative status was confirmed by a low level of reduced glutathione and alpha-tocopherol. DHEA treatment (4 mg per day for 3 weeks, per os) protected the synaptosomes against oxidative damage: synaptosomes from diabetic DHEA-treated rats showed a significant decrease in reactive species (P<0.05) and in the formation of end products of lipid peroxidation, evaluated in terms of fluorescent chromolipid (P<0.01). Moreover, DHEA treatment restored the unsaturated fatty acid content of the membrane and the reduced glutathione and alpha-tocopherol levels to normal levels and restored membrane NaK-ATPase activity close to control levels. The results demonstrate that DHEA supplementation greatly reduces oxidative damage in synaptosomes isolated from diabetic rats and suggest that this neurosteroid may participate in protecting the integrity of synaptic membranes against hyperglycaemia-induced damage.
Aragno
M
M
Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, 10125, Turin, Italy.
Parola
S
S
Tamagno
E
E
Brignardello
E
E
Manti
R
R
Danni
O
O
Boccuzzi
G
G
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D003687:Dehydroepiandrosterone / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology; D005609:Free Radicals / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy* / Q000209:etiology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D000975:Antioxidants; D005609:Free Radicals; D003687:Dehydroepiandrosterone; D013311:Streptozocin