Synaptosomes isolated from Goto-Kakizaki diabetic rat brain exhibit increased resistance to oxidative stress: role of vitamin E.
Increased oxidative stress is believed to be an important factor in the development of diabetic complications. In this study, the effect of diabetes on the susceptibility of synaptosomes to oxidative stress, induced by the oxidizing system ascorbate/Fe2+, on the activity of antioxidant enzymes and on the levels of glutathione and vitamin E was investigated. Synaptosomes were isolated from brain of 29-weeks-old Goto-Kakizaki (GK) rats, a model of non-insulin dependent diabetes mellitus and from normal Wistar rats. Synaptosomes isolated from GK rats displayed a lower susceptibility to lipid peroxidation, as assessed by quantifying thiobarbituric acid reactive substances (TBARS), than normal rats (5.33 +/- 0.79 and 7.58 +/- 0.7 nmol TBARS/mg protein, respectively). In the absence of oxidants, no significant differences were found between the levels of peroxidation in synaptosomes of diabetic or control rats. Superoxide dismutase (SOD), glutathione peroxidase and glutathione reductase activities were unaltered in the brain of diabetic rats. There were no statistically significant differences in fatty acid composition of total lipids and reduced glutathione levels in synaptosomes of diabetic and control rats. The decreased susceptibility to membrane lipid peroxidation of diabetic rats synaptosomes correlated with a 1.3-fold increase in synaptosomal vitamin E levels. Vitamin E levels in plasma were also higher in diabetic rats (21.32 micromol/l) as compared to normal rats (15.13 micromol/l). We conclude that the increased resistance to lipid peroxidation in GK rat brain synaptosomes may be due to the increased vitamin E content, suggesting that diabetic animals might develop enhanced defense systems against brain oxidative stress.
Santos
M S
MS
Department of Zoology, Center for Neurosciences of Coimbra, University of Coimbra, Portugal.
Duarte
A I
AI
Matos
M J
MJ
Proença
T
T
Seiça
R
R
Oliveira
C R
CR
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007501:Iron / Q000494:pharmacology; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*; D014810:Vitamin E / Q000097:blood / Q000378:metabolism*
D005227:Fatty Acids; D014810:Vitamin E; D007501:Iron; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione; D001205:Ascorbic Acid