Free Radicals, Antioxidants and Diabetes: Embryopathy, Retinopathy, Neuropathy, Nephropathy and Cardiovascular Complications

Abstract

The metabolic disturbances in the insulin-dependent diabetes mellitus or type 1 and noninsulin-dependent diabetes mellitus or type 2 are associated with a number of complications including cardiovascular diseases, nephropathy, neuropathy, retinopathy leading to blindness and embryopathy or congenital malformations. Maternal diabetes is associated with a high incidence of congenital malformations and fetal abortions. Heart and kidney anomalies, along with central nervous system defects are frequent manifestations of a maternal diabetic environment. Glycation products from excess glucose can chemically modify DNA causing mutations and complex DNA rearrangements. Therefore, DNA damage in fetal tissues as a result of maternal diabetes may reflect a level of genomic injury sufficient to affect embryonic development. The formation of advanced glycation end products can accelerate vascular occlusion by quenching the vasodilating agent nitric oxide. Interaction with high-affinity receptors located on monocytes and macrophages can enhance the production of free radicals and reactive oxygen/nitrogen species, the secretion of tumor necrosis factor-α, interleukin-1 and insulin-like growth factor 1 which can proliferate endothelial, mesangial and smooth muscle cells and hence contribute significantly to the pathogenesis of cardiovascular complications. Retinopathy is characterized by increased vascular permeability, by vascular closure, together with the growth of new blood vessels on the retina and posterior surface of the vitreous. Reactive oxygen species are involved in decreased retinal blood flow, increased vascular permeability and disruption of blood-retinal barrier. The involvement of oxidative stress in the pathology of diabetes from its associated cardiovascular dysfunctions, nephropathy, neuropathy, retinopathy (leading to blindness) and embryopathy or congenital malformations, suggests that potential management of diabetes could benefit from use of dietary biofactors in medicinal and food plants. There is therefore a requirement for research to focus on the molecular mechanisms of action of extracts and/or the biofactors flavonoids, proanthocyanidins, alkaloids, etc. derived from these plants.

Reactive oxygen species, reactive nitrogen species and antioxidants in etiopathogenesis of diabetes mellitus type-2

“…The non-vascular complications include cataracts, glaucoma etc. OS has been implicated in all vascular complications and in some non-vascular complications especially cataract (14,15,16,73). The glycemic control may prevent or delay the complications but in any case it does not guarantee for it.…”

“…Diabetes mellitus with an alarmingly rising incidence (1) is a cluster of abnormal metabolic paradigm having a common of environmental factors which may act independently or in concert with genetic disposition, fifth, in due course of time a large number of DMT-2 patients develop multiple macro-or micro-vascular complications or both, sixth, the new molecular mechanisms involved in pathogenesis of the disease are now emerging, are more vigorously investigated and their interaction among themselves and their superimposition or intertwining with genetic factors are being critically evaluated, yet the etiopathogenesis of the disease is not fully understood (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Obviously, clinicians have limited armamentarium for the treatment of the disease, and so far no drug is known to cure it permanently.…”

“…In the next phase, beta-cell dysfunction develops (17,18,(38)(39)(40). Cells in various tissues develop metabolic stress of various types with varying magnitude which may culminate in diabetic complications (12,16,(41)(42)(43)(44)(45)(46). A diabetic person can develop one or more types of complications (2,16).…”

“…Cells in various tissues develop metabolic stress of various types with varying magnitude which may culminate in diabetic complications (12,16,(41)(42)(43)(44)(45)(46). A diabetic person can develop one or more types of complications (2,16). The risk factors can be divided into two groups, first, which initiate diabetic risk and second the intervening risk factors which join later and abet the progression of diabetes and diabetic complications.…”

“…In brief, several diverse mechanisms converge to cause DMT-2 and many of these and some of the supervening mechanisms ramify to cause complications (47). In the recent years an attractive hypothesis has developed, albeit not completely proven, that ROS and RNS could be a decisive risk force in the initiation of DMT-2 especially through insulin resistance (27) and obesity (21) and in development of diabetic complications due to chronic enraged OS (16). This chronic raised OS is reported to be due to several reasons such as increased formation of Advanced Glycation End Products (AGEs) and defect in a receptor for AGEs (RAGE), glucose autoxidation, increased diversion of glucose to sorbitol (polyol pathway) and hexosamine stimulated secretion of several proinflammatory cytokines, particularly Tumor Necrosis Factor Alpha (TNFD) and several other interleukins (Fig 3).…”