赤血球酸化ストレスに対するアルドース還元酵素阻害剤の効果

概要

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Aldose reductase (AR), an enzyme in the polyol pathway of glucose metabolism, catalyzes the reduction of glucose to sorbitol. In diabetes mellitus, the increased availability of glucose in insulin insensitive tissues such as lens, nerve and retina leads to increased formation of sorbitol through the polyol pathway. The sorbitol accumulation may be contribute to oxidative stress by depleting its cofactor NADPH, which is also required for the regenerating of GSH. In this study we investigated the role of polyol pathway for oxidative stress in human erythrocytes and the effect of aldose reductase inhibitor (ARI). The erythrocytes incubated in the presence of 30mM glucose, the time course of sorbitol accumulation appeared almost linear over the 3 hr incubation period. Whereas, the sorbitol accumulation was effectively inhibited during incubation with high concentration of glucose by the ARI Moreover, the treatment with ARl was prevented decrease of GSH in exposure to H_20_2. These results suggested that the abnormal glutathione redox cycle observed in human erythrocytes is induced by high glucose concentration, resulting in an impairment of reduced GSH-dependent H_20_2 degradation.
香川県立保健医療大学の論文