Alterations in tissue antioxidant systems in the spontaneously diabetic (BB Wistar) rat

Wohaieb, Saleh A.; Godin, David V.

doi:10.1139/y87-346

Cited by 43 publications

(26 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cardiac tissue exposed to ambient high glucose may initially mount a defense response by augmenting the antioxidant system. In fact, the levels of GSH in STZ-induced or insulin-dependent spontaneously diabetic rats were elevated in the heart (40,41), although there are some reports showing the opposite results (42,43). Such discrepancy in the cardiac GSH among the diabetic models may be due to the duration of hyperglycemia at the time when the GSH level was measured.…”

Section: Discussionmentioning

confidence: 98%

The Activity of Aldose Reductase Is Elevated in Diabetic Mouse Heart

et al. 2007

View full text Add to dashboard Cite

Abstract. The importance of aldose reductase (AR) has been implicated in the pathogenesis of diabetic complications, although the alterations in the expression and activity of AR during hyperglycemia in the heart have not been well characterized. We investigated the expression and enzyme activity of AR in a murine diabetic model. Three weeks after the induction of hyperglycemia with streptozotocin, the level of AR mRNA was significantly reduced in the cardiac ventricles of BDF-1 mice. In contrast, the activity of AR was significantly elevated in the heart without any significant change in the protein level. In these mice, the level of cardiac thiobarbituric acid-reactive substances was unaltered, whereas the level of reduced glutathione (GSH) was significantly increased. Daily administration of insulin for 3 weeks completely normalized the level of AR mRNA and the enzyme activity. On the other hand, daily administration of an antioxidant, N-acetylcysteine significantly reduced the level of AR mRNA in the heart with a concomitant elevation in the enzyme activity. These results suggest that the activity of AR in the heart is affected by GSH dynamics. Augmented AR activity at the early stage of hyperglycemia may perturb glycolysis and affect cardiac performance.

show abstract

Section: Discussionmentioning

confidence: 98%

The Activity of Aldose Reductase Is Elevated in Diabetic Mouse Heart

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Prior studies using cardiac tissue or cardiomyocytes from animal models of diabetes demonstrated upregulation of antioxidant enzymes (14), increased production of hydrogen peroxide (41), and increased lipid peroxidation (12,13). Recently, oxidative stress in diabetic human hearts has been shown (42) by the finding of elevated levels of the marker of oxidative damage, nitrotyrosine, in biopsies from diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

“…The heart is a susceptible target because it contains low levels of free radical scavengers (11). Available evidence implicating ROS in diabetic cardiomyopathy include increased cardiac lipid peroxidation (12,13) and elevated expression of genes for the antioxidants catalase (12,14,15) and heme oxygenase (16). Also, functional or morphological damage to diabetic hearts can be reduced with oral or systemic antioxidant administration (12,17).…”

mentioning

confidence: 99%

Overexpression of Metallothionein Reduces Diabetic Cardiomyopathy

et al. 2002

View full text Add to dashboard Cite

Many diabetic patients suffer from cardiomyopathy, even in the absence of vascular disease. This diabetic cardiomyopathy predisposes patients to heart failure and mortality from myocardial infarction. Evidence from animal models suggests that reactive oxygen species play an important role in the development of diabetic cardiomyopathy. Our laboratory previously developed a transgenic mouse model with targeted overexpression of the antioxidant protein metallothionein (MT) in the heart. In this study we used MT-transgenic mice to test whether an antioxidant protein can reduce cardiomyopathy in the OVE26 transgenic model of diabetes. OVE26 diabetic mice exhibited cardiomyopathy characterized by significantly altered mRNA expression, clear morphological abnormalities, and reduced contractility under ischemic conditions. Diabetic hearts appeared to be under oxidative stress because they had significantly elevated oxidized glutathione (GSSG). Diabetic mice with elevated cardiac MT (called OVE26MT mice) were obtained by crossing OVE26 transgenic mice with MT transgenic mice. Hyperglycemia in OVE26MT mice was indistinguishable from hyperglycemia in OVE26 mice. Despite this, the MT transgene significantly reduced cardiomyopathy in diabetic mice: OVE26MT hearts showed more normal levels of mRNA and GSSG. Typically, OVE26MT hearts were found to be morphologically normal, and elevated MT improved the impaired ischemic contractility seen in diabetic hearts. These results demonstrate that cardiomyocyte-specific expression of an antioxidant protein reduces damage to the diabetic heart. Diabetes 51:174 -181, 2002

show abstract

“…It has been reported that increased free-radical mediated oxidative stress is associated with diabetic complications in both humans and animals [4,[12][13][14][15][16]. Reactive Oxygen Species (ROS) or Free Oxygen Radicals (FOR's) such as superoxide radical (O 2 -), hydroxyl radical (OH -), and hydrogen peroxide (H 2 O 2 ), generated during oxygen metabolism, are controlled by various cellular defense mechanisms consisting of enzymatic [(superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSHPx)] and non-enzymatic (vitamin E, β-carotene, vitamin C) antioxidants [17].…”

Section: Introductionmentioning

confidence: 99%