Active oxygen-induced vascular damage and its protection.

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1. Dietary vitamin E reduced the decreases of the histamin-induced, endothelium-dependent vasodilatation and associated production of cGMP in rat thoracic aorta induced by increase of age(from 3-weeks to 40-weeks). The level of plasma lipid peroxides increased with increase of age was further increased in vitamin E-deficient rats and decreased in vitamin E-supplemented rats. Histamin-induced vasodilatation and cGMP formation in E-deficient rats were decreased with increase of lipid peroxides in aorta by incubation with ascorbic acid and Fe^<2+>, which are known to initiate lipid peroxidation in vitro. The decreases of vasodilatation and cGMP synthesis by lipid peroxidation were suppressed in E-supplemented rats. These results indicate that vitamin E may have a protective effect on decrease -of vasodilatation associated with age and in vitro lipid peroxidation due to its antioxidant activity.2. Dietary vitamin E protected the fetal ischemic distress induced by clampig, the uterotubal ve … More ssels of pregnant rats, possibly by inhibiting lipid peroxidation increased in the fetal tissues such as brain by reperfusion after ischemia. Moter disturbances induced by ischemic compression injury of rat spinal cord were reduced by vitamin E-supplementation, but enhanced by vitamin E deficiency. The increase in the level of lipid peroxides in the spinal cord by reperfusion after ischemia increased with decrease in the dietary level of vitamin E.3. The site-specific mechanism of initiation of H202-dependent, lipid peroxidedependent and peroxide-independent lipid peroxidations catalyzed by chelatediron in micelle membranes was investigated. Among the chelaters examined such as EDTA, EGTA, DETAPAC, and deferoxamine, iron-NTA(nitrilotriacetic acid), which was reported to have carcinogenic effect in kidney, showed the highest activity for the initiation of these three lipid peroxidations, suggesting that the strong prooxidant effects of iron-NTA is a major cause of its renal carcinogenicity. Less