Oxidative Stress: Pathogenetic Role in Diabetes Mellitus and Its Complications and Therapeutic Approaches to Correction

Abstract

The review presents modern views about the role of oxidative stress reactions in the pathogenesis of types 1 and 2 diabetes mellitus and their complications based on the analysis of experimental and clinical studies. The sources of increased ROS generation in diabetes are specified, including the main pathways of altered glucose metabolism, oxidative damage to pancreatic β-cells, and endothelial dysfunction. The relationship between oxidative stress, carbonyl stress, and inflammation is described. The significance of oxidative stress reactions associated with hyperglycemia is considered in the context of the “metabolic memory” phenomenon. The results of our studies demonstrated significant ethnic and age-related variability of the LPO—antioxidant defense system parameters in patients with diabetes mellitus, which should be considered during complex therapy of the disease. Numerous studies of the effectiveness of antioxidants in diabetes mellitus of both types convincingly proved that antioxidants should be a part of the therapeutic process. Modern therapeutic strategies in the treatment of diabetes mellitus are aimed at developing new methods of personalized antioxidant therapy, including ROS sources targeting combined with new ways of antioxidant delivery.

Content of Carbonyl Compounds and Parameters of Glutathione Metabolism in Men with Type 1 Diabetes Mellitus at Preclinical Stages of Diabetic Nephropathy

“…These compounds are the precursors of a natural dicarbonyl methylglyoxal, a precursor of advanced glycation endproducts (AGE) [10]. Methylglyoxal, along with glyoxal, bind to different AGE receptors or interact with biomolecules, thus causing oxidative stress directly or indirectly through the activation of PKC [1,7].…”

“…It is known that GR, as a homodimeric enzyme, restores the disulfide bond of oxidized glutathione to its sulfhydryl form GSH. GR is also important in the formation of innate immunity [1,4]. GPx, in addition to hydroperoxides, recycles most of the phospholipid peroxides and fatty acids using glutathione.…”

“…An important factor in the development of diabetic complications is oxidative glycosylation that includes glucose autooxidation, formation of dicarbonyl intermediates, and binding of oxidized carbohydrates to proteins [10]. The accumulation of natural dicarbonyls (methylglyoxal and TBA-reactive substances), secondary reaction products of free radical oxidation of lipids and carbohydrates can contribute to the modification and disruption of normal metabolism of vari-ous cell biomolecules [1,13]. Glutathione-dependent enzymes, the main component of the antioxidant defense (AOD), are evolutionarily programmed to optimize the balance between oxidative processes and the activity of various AOD systems [4,8].…”

Diabetes and Alzheimer’s Disease: Might Mitochondrial Dysfunction Help Deciphering the Common Path?

“…The wide number of “antioxidants” evaluated as potential preventative strategies in diabetes and AD emphasizes the crucial role attributed to redox imbalance in the pathogenesis of both diseases [ 227 , 228 ]. Most of these molecules are natural compounds such as polyphenols, known to attenuate the ROS and RNS levels and counteract the increased production of advanced glycation end products (AGEs) at the sites of inflammation [ 229 ].…”

Sterculia tragacantha Lindl Leaf Extract Ameliorates STZ-Induced Diabetes, Oxidative Stress, Inflammation and Neuronal Impairment

“…High generations of free radicals coupled with depleted levels of endogenous antioxidants result in the impairment of cellular organelles, excessive lipid peroxidation, destruction of pancreatic β-cells, oxidative stress and development of diabetic condition. 4 The progression of diabetes complications is characterized by the development of certain pathological conditions including nephropathy, retinopathy, and neuropathy. 5 Early and adequate management of these diseases are critical to the prevention of diabetes-induced pathological impairments of nerve tissues and other vital organs.…”