Other Mechanisms of Tissue Damage in Diabetes Involving Free Radicals

4 Other Mechanisms of Tissue Damage in Diabetes INVOLVING Free Radicals 

Further research is required to establish whether free-radical-induced damage is a primary event in diabetes. Tissue damage, which is associated with inactivation of antioxidants and release of metal ions that are potent catalysts of free radical reactions, can lead to lipid peroxidation. This raises the possibility that the diabetic process itself or other frctors may increase free-radical activity following direct tissue damage. 

Essential hypertension, whose prevalence is increased nearly two-fold in the diabetic population, may be another source of free-radical activity. The vascular lesions of hypertension can be produced by free-radical reactions (Selwign, 1983). In the recent Kuopio Ischaemic Heart Risk Factor Study in Finnish men, a marked elevation of blood pressure was associated with low levels of both plasma ascorbate and serum selenium (Salonen etal., 1988). A few studies report a hypotensive effect of supplementary ascorbate in patients with hypertension, but the actual changes in both systolic and diastolic pressure after ascorbate were not statistically significant in comparison with placebo (Trout, 1991). 

However, it remains a valid argument (as in the case of atheroma) that increased oxidative stress may be secondary to (rather than a cause of) endothelial damage in hypertension due to other mechanisms. 

Free radicals are by-products of prostaglandin metabolism and may even regulate the activity of the arachidonate pathway. Arachidonic acid, released from lipids as a result of activation of phospholipases by tissue injury or by hormones, may be metabolized by the prostaglandin or leu-kotriene pathways. The peroxidase-catalysed conversion of prostaglandin G2 to prostaglandin H2 (unstable prostanoids) and the mechanism of hydroperoxy fatty acid to the hydroxy fatty acid conversion both yield oxygen radicals, which can be detected by e.s.r. (Rice-Evans et al., 1991). 

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