Globally, Diabetes mellitus is a metabolic disorder and its complications are leading causes of death. According to diabetes prevalence around 47.3% of Indiaâ€™s 70 million diabetics people suffer from diabetes and that are not diagnosed and do not know they have high blood glucose levels that, if left untreated, lead to complications such as blindness, kidney failure, heart disease, stroke and foot amputation. Acute complications include from hyperglycemia, which causes damage to blood vessels and peripheral nerves, greatly increasing the risk of heart attack.
Aldose reductase (AR, EC 188.8.131.52) plays a key role in the development of diabetic complications it is a rate-controlling enzyme in the polyol pathway and a potential target for drug design. In the polyol pathway, AR initially catalyzes the NADPH-dependent reduction of the aldehyde form of glucose to form sorbitol. Sorbitol dehydrogenase then utilizing NAD oxidizes the intermediate sorbitol to fructose. The polyol metabolic pathway produces elevated accumulation of cellular sorbitol leading to osmotic stresses on cells, and is then implicated mainly in microvascular damage to retina, kidney, and nerve systems.
Though the inhibition of aldose reductase has basic approach to the prevention and treatment of diabetic complications. The potential aldose inhibitors are Tolrestat, Zopolrestat, Zenarestat and ponarestat and sorbinil and etc.
Furthermore, recent studies have shown that AR inhibitors may be able to prevent diabetic complications. In this review, we will focus on describing vital roles of AR in the physiology and pathogenesis of diabetic complications, and the potential use of AR inhibitors as a therapeutic strategy in preventing diabetes complications