Department of Pharmacology, Institute of Pharmaceutical Research, GLA University Mathura, Uttar Pradesh, India.
Curr Pharm Biotechnol. 2024;25(9):1073-1081. doi: 10.2174/1389201025666230830125147.
The expression of aldose reductase leads to a variety of biological and pathological effects. It is a multifunctional enzyme which has a tendency to reduce aldehydes to the corresponding sugar.alcohol. In diabetic conditions, the aldose reductase enzyme converts glucose into sorbitol using nicotinamide adenine dinucleotide phosphate as a cofactor. It is a key enzyme in polyol pathway which is a surrogate course of glucose metabolism. The polyol pathway has a significant impact on the aetiology of complications in individuals with end-stage diabetes. The exorbitant level of sorbitol leads to the accumulation of intracellular reactive oxygen species in diabetic heart, neurons, kidneys, eyes and other vasculatures, leading to many complications and pathogenesis. Recently, the pathophysiological role of aldose reductase has been explored with multifarious perspectives. Research on aldose reductase suggest that besides implying in diabetic complications, the enzyme also turns down the lipid-derived aldehydes as well as their glutathione conjugates. Although aldose reductase has certain lucrative role in detoxification of toxic lipid aldehydes, its overexpression leads to intracellular accumulation of sorbitol which is involved in secondary diabetic complications, such as neuropathy, cataractogenesis, nephropathy, retinopathy and cardiovascular pathogenesis. Osmotic upset and oxidative stress are produced by aldose reductase via the polyol pathway. The inhibition of aldose reductase alters the activation of transcription factors like NF-ƙB. Moreover, in many preclinical studies, aldose reductase inhibitors have been observed to reduce inflammation-related impediments, such as asthma, sepsis and colon cancer, in diabetic subjects. Targeting aldose reductase can bestow a novel cognizance for this primordial enzyme as an ingenious strategy to prevent diabetic complications and associated morbidities. In this review article, the significance of aldose reductase is briefly discussed along with their prospective applications in other afflictions.
醛糖还原酶的表达导致了多种生物学和病理学效应。它是一种多功能酶，具有将醛还原为相应的糖醇的趋势。在糖尿病情况下，醛糖还原酶利用烟酰胺腺嘌呤二核苷酸磷酸作为辅助因子将葡萄糖转化为山梨糖醇。它是多元醇途径的关键酶，是葡萄糖代谢的替代途径。多元醇途径对终末期糖尿病患者并发症的发病机制有重要影响。过多的山梨糖醇导致糖尿病心脏、神经元、肾脏、眼睛和其他血管中的细胞内活性氧物质积累，导致许多并发症和发病机制。最近，醛糖还原酶的病理生理学作用已经从多个角度进行了探索。醛糖还原酶的研究表明，除了暗示糖尿病并发症外，该酶还能降低脂质衍生的醛以及它们的谷胱甘肽缀合物。尽管醛糖还原酶在解毒毒性脂质醛方面具有一定的有益作用，但它的过度表达会导致山梨糖醇的细胞内积累，这与糖尿病的继发性并发症有关，如神经病变、白内障形成、肾病、视网膜病变和心血管发病机制。醛糖还原酶通过多元醇途径产生渗透失衡和氧化应激。转录因子 NF-ƙB 的激活被醛糖还原酶改变。此外，在许多临床前研究中，醛糖还原酶抑制剂已被观察到可减少糖尿病患者与炎症相关的障碍，如哮喘、败血症和结肠癌。针对醛糖还原酶可以为这种原始酶提供新的认识，作为预防糖尿病并发症和相关疾病的一种巧妙策略。在这篇综述文章中，简要讨论了醛糖还原酶的意义及其在其他疾病中的潜在应用。
