The antioxidative potential of cerebral microvessels in experimental diabetes mellitus.
To determine if experimental diabetes is associated with decreased antioxidative potential along with increased peroxidation of lipids in cerebral microvessels, streptozotocin-induced diabetic rats were compared with control rats and to diabetic rats treated with insulin. Isolated cerebral microvessels from diabetic rats had significantly higher concentrations of malondialdehyde (MDA; micrograms/mg protein) (0.0283 +/- 0.0017) compared with control (0.0201 +/- 0.0016) or insulin-treated diabetic 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 monitoring of the fluorescence of phycoerythrin at 37 degrees C. The free radical quenching activity of cerebral microvessels expressed as % inhibition of phycoerythrin oxidation by AAPH was significantly reduced in diabetic rats (38.7 +/- 4.5%) compared with control (54.3 +/- 4.9%) or insulin-treated diabetic rats (57.6 +/- 2.9%) (P < 0.01). The % inhibition of oxidation by cerebral microvessels in the presence of CuSO4 was only 15.7 +/- 3.1% and did not differ significantly in diabetic rats (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 of lipid peroxidation byproducts. Increased oxidative stress may be one of the many mechanisms underlying the diabetes-related changes in the blood-brain barrier.
Mooradian
A D
AD
St. Louis VA Medical Center, MO, USA.
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005609:Free Radicals; D007328:Insulin / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008833:Microcirculation / Q000378:metabolism; D010799:Phycoerythrin / Q000494:pharmacology; D016548:Prosencephalon / Q000098:blood supply*; D051381:Rats; D011916:Rats, Inbred F344
D000578:Amidines; D000975:Antioxidants; D005609:Free Radicals; D007328:Insulin; D010799:Phycoerythrin; D008315:Malondialdehyde; C046728:2,2'-azobis(2-amidinopropane)