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.