THE ANTIOXIDATIVE POTENTIAL OF CEREBRAL MICROVESSELS IN EXPERIMENTAL DIABETES-MELLITUS

To determine if experimental diabetes is associated with decreased ant ioxidative potential along with increased peroxidation of lipids in ce rebral microvessels, streptozotocin-induced diabetic rats were compare d with control rats and to diabetic rats treated with insulin. Isolate d cerebral microvessels from diabetic rats had significantly higher co ncentrations of malondialdehyde (MDA; mu g/mg protein) (0.0283 +/- 0.0 017) compared with control (0.0201 +/- 0.0016) or insulin-treated diab etic rats (0.196 +/- 0.0022) P < 0.01. The antioxidative potential was measured in the presence of a peroxy radical generator 2,2'-azobis(2- amidinopropane) (AAPH) and hydroxyl radical generator CuSO4 with monit oring of the fluorescence of phycoerythrin at 37 degrees C. The free r adical quenching activity of cerebral microvessels expressed as % inhi bition of phycoerythrin oxidation by AAPH was significantly reduced in diabetic rats (38.7 +/- 4.5%) compared with control (54.3 +/- 4.9%) o r insulin-treated diabetic rats (57.6 +/- 2.9%) (P < 0.01). The % inhi bition of oxidation by cerebral microvessels in the presence of CuSO4 was only 15.7 +/- 3.1% and did not differ significantly in diabetic ra ts (13.1 +/- 2.1%). The results indicate that antioxidative potential of cerebral microvessels, especially in the presence of peroxy radical generator, is reduced in diabetes along with increased accumulation o f lipid peroxidation byproducts. Increased oxidative stress may be one of the many mechanisms underlying the diabetes-related changes in the blood-brain barrier.