Oxidative stress, diabetic

Ceriello A, dello Russo P, Amstad P, Cerutti P. High glucose induces antioxidant enzymes in human endothelial cells in culture. Evidence linking hyperglycemia and oxidative stress. Diabetes 1996 45 471 77. 

It has been proposed that the development of the complications of diabetes mellitus may be linked to oxidative stress and therefore might be attenuated by antioxidants such as vitamin E. Furthermore, it is discussed that glucose-induced vascular dysfunction in diabetes can be reduced by vitamin E treatment due to the inactivation of PKC. Cardiovascular complications are among the leading causes of death in diabetics. In addition, a postulated protective effect of vitamin E (antioxidants) on fasting plasma glucose in type 2 diabetic patients is also mentioned but could not be confirmed in a recently published triple-blind, placebo-controlled clinical trial [3]. To our knowledge, up to now no clinical intervention trials have tested directly whether vitamin E can ameliorate the complication of diabetes. 

Collier et al. (1990) extended their studies relating to oxidative stress and diabetes by demonstrating that the levels of several free-radical scavengers (red cell superoxide dismutase, plasma thiols) were significantly reduced in 22 type 2 diabetic patients (mean age 53 years) in comparison with 15 control subjects (mean age 51 years). No significant diflFerences in red cell lysate thiols or... 

In a recent study, serum ascorbate concentrations were significantly reduced in a group of elderly diabetic patients (w = 40, mean age 69 years) in comparison with an age-matched group of non-diabetic controls ( = 22, mean age 71 years), and this reduction was more pronounced in those patients with microangiopathy (Sinclair et al., 1991). Diabetic patients were shown to have a high serum dehydroascorbate/ascorbate ratio indicative of increased oxidative stress. Ascorbate deficiency was partially corrected by vitamin C supplementation, 1 g daily by mouth, but the obvious disturbance in ascorbate metabolism in the diabetic patients was accentuated, since serum ascorbate concentrations fell (after the initial rise) despite continued vitamin C supplementation (Fig. 12.3). 

It should be remembered that some of the established antioxidants have other metabolic roles apart from free-radical scavenging. The finding of reduced antioxidant defences in diabetes, for example, may not be prima fascie evidence of increased oxidative stress, since alternative explanations may operate. For example, this may reflect a response to reduced free-radical activity as su ested by the results of a previous study (Collier et al., 1988). In the case of ascorbate, an alternative explanation has been proposed by Davis etal. (1983), who demonstrated competitive inhibition of ascorbate uptake by glucose into human lymphocytes. This view is supported by the similar molecular structure of glucose and ascorbic acid (see Fig. 12.4) and by a report of an inverse relationship between glycaemic control and ascorbate concentrations in experimental diabetes in rats. Other investigators, however, have not demonstrated this relationship (Som etal., 1981 Sinclair etal., 1991). 

Other considerations such as demonstrating a direct correlation between the level of oxidative stress and tissue damage in diabetes and showing that antioxidant therapy leads to prevention, arrest or regression of diabetic complications are also important and must be the basis of future well-designed studies. 

Baynes, J.W. (1991). The role of oxidative stress in the development of complications in diabetes. Diabetes 40, 405-412. 

Wolff, S.P. (1987). The potential role of oxidative stress in diabetes and its complications novel implications for theory and therapy. In Diabetic Complications Scientific and Clinical Aspects (ed. M.J.C. Crabbe) pp. 167-221. Churchill Livingstone, Edinburgh. 

M.A. Yorek, The role of oxidative stress in diabetic vascular and neural disease. Free Rad. Res. 37, 471-480 (2003). 

Hydroxy-10,12-octadecadienoic acid, which is formed by the reduction of 9-HPODE, was identified in the erythrocyte membrane phospholipid of diabetic patients [83]. It was suggested that this compound was formed as a result of glucose-induced oxidative stress in the reaction of hydroxyl radicals with linoleic acid. 

Vitamin B6 (pyridoxine) and its derivative pyridoxamine are apparently able to inhibit superoxide production, reduce lipid peroxidation and glycosylation in high glucose-exposed erythrocytes [353], It was suggested that the suppression of oxidative stress in erythrocytes may be a new mechanism by which these natural compounds inhibit the development of complication in diabetes mellitus. 

As in the case of other cardiovascular diseases, the possibility of antioxidant treatment of diabetes mellitus has been studied in both animal models and diabetic patients. The treatment of streptozotocin-induced diabetic rats with a-lipoic acid reduced superoxide production by aorta and superoxide and peroxynitrite formation by arterioles providing circulation to the region of the sciatic nerve, suppressed lipid peroxidation in serum, and improved lens glutathione level [131]. In contrast, hydroxyethyl starch desferrioxamine had no effect on the markers of oxidative stress in diabetic rats. Lipoic acid also suppressed hyperglycemia and mitochondrial superoxide generation in hearts of glucose-treated rats [132],... 

Oxidative stress is implicated in a range of health concerns, including diabetes mel-litus, cancer, and cardiovascular disease among many other degenerative diseases... 

Yamabe N, Kang KS, Park CH, Tanaka T, Yokozawa T. (2009) 7-0-galloyl-D-sedoheptulose is a novel therapeutic agent against oxidative stress and advanced glycation endproducts in the diabetic kidney. Biol Pharm Bull 2il 657-664. 

Patients with both type 1 and type 2 diabetes are prone to complications. The specific chronic diabetic complications are due to microangiopathy and include neuropathy, retinopathy and nephropathy. Recent data stress the vital role of hyperglycaemia and oxidative stress in their pathophysiology. Premature atherosclerosis (which can be considered... 

Cigarette smoking is a major risk factor for coronary disease. It is associated with reduced levels of HDL, impairment of cholesterol retrieval, cytotoxic effects on the endothelium, increased oxidation of lipoproteins, and stimulation of thrombogenesis. Diabetes, also a major risk factor, is another source of oxidative stress. 

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