Loss of α‐tocopherol upon exposure to nitric oxide or the sydnonimine SIN‐1

Groot, Herbert de; Hegi, Udo; Sies, Helmut

doi:10.1016/0014-5793(93)81150-x

Cited by 82 publications

(35 citation statements)

References 29 publications

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“…In this context a report by de Groot et al is of interest showing that in a lipophilic solvent c~-tocopherol is oxidized to its quinone derivative when in contact with NO gas [27]. Furthermore, it was found that ~-tocopherol in low-density lipoprotein is oxidized by peroxynitrite, a product of the reaction between nitric oxide and superoxide [28].…”

Section: Discussionmentioning

confidence: 97%

Suppression of nitric oxide toxicity in islet cells by α‐tocopherol

et al. 1995

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We show here that preincubation of pancreatic islet cells with a-toeopherol significantly improves their resistance to toxic doses of nitric oxide (NO). No protection was afforded by other antioxidants such as vitamin C or glutathione-monoethyl ester. The pathway of NO induced islet cell death involves DNA damage and excessive activation of poly(ADP-ribose)polymerase leading to irreversible depletion of intraeellular NAD +. a-Tocopherol was found to interfere at early steps of this pathway, by preventing the occurrence of DNA strand breaks. This indicates that a-tocopherol directly interacts with NO or its reactive intermediates. We conclude that a-tncopherol is not only part of the cellular defence system against oxygen radicals but also protects eukaryotie cells from NO toxicity.

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Section: Discussionmentioning

confidence: 97%

Suppression of nitric oxide toxicity in islet cells by α‐tocopherol

et al. 1995

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“…NO (itself a free radical) could be directly scavenged by the high concentrations of a-tocopherol present in the plasma membrane of vascular smooth muscle cells of the treated animals [32,33]. The further impairment of vascular function in rats on the combined vitamin E and C diet may reflect the increased availability of reduced vitamin E to quench NO.…”

Section: Discussionmentioning

confidence: 99%

Dietary antioxidant supplementation reduces lipid peroxidation but impairs vascular function in small mesenteric arteries of the streptozotocin-diabetic rat

et al. 1998

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Insulin-dependent diabetes mellitus (IDDM) is associated with abnormal function of the vascular endothelium and it is proposed that this defect could underlie many of the associated vasculopathies [1]. Studies from our laboratory and others have reported impaired vasodilatory responses to the endothelium-dependent vasodilator acetylcholine (ACh) in isolated arteries from diabetic subjects [2] and in mesenteric [3], femoral [4] and aortic [5] arteries from the streptozotocin (STZ)-diabetic rat (an animal model of uncontrolled IDDM). Although a physiological endothelium-dependent dilatory role of ACh has sometimes been questioned, the reduced relaxation of arteries from diabetic animals to other endothelium-dependent dilators [1] and to increasing luminal flow [6] would suggest that the poor ACh responses reflect a generalised endothelial defect. The abnormal ACh response is likely to result from either decreased nitric oxide (NO) synthesis or increased NO degradation [3,4]. Several mechanisms have been hypothesised, among which is the suggestion that oxidative stress could play an important role [7,8]. Diabetologia (1998) Summary Impaired endothelium-dependent relaxation could underlie many of the vascular complications associated with insulin-dependent diabetes mellitus, and may be mediated by increased oxidative stress. The effect of antioxidants on vascular endothelial function and oxidative stress of streptozotocin-diabetic rats was assessed by dietary supplementation with vitamins E and C. Diabetic (i. v. streptozotocin, 45 mg/kg) male Sprague-Dawley rats were fed one of six supplemented diets containing 75.9, 250, or 500 mg vitamin E/kg chow, 250 mg vitamin C/kg H 2 0, 250 mg vitamin E/kg chow plus 250 mg vitamin C/kg H 2 O, or chow deficient in vitamin E, and then compared to standard-fed control rats. After 4 weeks, small mesenteric arteries were dissected and mounted on a small vessel myograph, concentration response curves were then constructed to noradrenaline, acetylcholine and sodium nitroprusside. Acetylcholinemediated relaxation was impaired in arteries from diabetic rats (pEC 50 6.701 ± SEM 0.120, n = 8) compared to controls (7.386 ± 0.078, n = 6; p < 0.05). The 500 mg/kg vitamin E diet further impaired maximum relaxation to acetylcholine (58.2 ± 10.5 vitamin E, n = 7 vs 84.4 ± 5.3 % standard, p < 0.05), and the combined vitamin E plus C diet impaired maximum relaxation to sodium nitroprusside (48.5 ± 4.1 in vitamin E + C, n = 8 vs 75.6 ± 3.9 % standard; p < 0.01). However, plasma 8-epi-prostaglandin (PG)F 2 a (measured as an estimate of oxidative stress) was dose-dependently decreased in rats on vitamin E supplemented diets. Dietary antioxidant supplementation did not reverse impaired endothelial function in this model of uncontrolled diabetes despite a concomitant decrease in oxidative stress. [Diabetologia (1998) 41: 148±156]

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“…This oxidation of c~-tocopherol was substantially inhibited by SOD (Table II), which is consistent with the hypothesis that the oxidant is either peroxynitrite or its decomposition products. It has long been known that NO 2 oxidises 0~-tocopherol to c~-tocopheroquinone and it has also been suggested that the direct reaction of nitric oxide and e-tocopherol results in the formation of tocopheroquinone [25,30]. However, under the conditions described here, and by others, little loss of ~-tocopherol by reaction with NO was detected, suggesting that either the reaction of NO with oxygen to form NO 2 is inefficient compared to its formation via the decomposition of peroxynitrite, or the oxidising agent is peroxynitrite or the hydroxyl radical (Table II and [14,20]).…”

Section: Resultsmentioning

confidence: 99%

The oxidation of α‐tocopherol in human low‐density lipoprotein by the simultaneous generation of superoxide and nitric oxide

et al. 1993

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Peroxynitrite is the product of the reaction between nitric oxide and superoxide. It is an oxidant which can also decompose to form the hydroxyl radical and nitrogen dioxide. In this report we show that a powerful oxidant with reactivity similar to that of the hydroxyl radical is formed from the generation of superoxide from xanthine oxidase and nitric oxide from S-nitroso-n-acetylpenicillamine (SNAP). Simultaneous generation of these two radicals by either xanthine oxidase/SNAP or the sydnonimine SIN-1 in the presence of low-density lipoprotein (LDL) results in the depletion of c~-tocopherol and formation of its oxidised product a-tocopheroquinone. The mechanism of oxidation required both the formation of nitric oxide and superoxide. In contrast to the promotion of LDL oxidation by transition metals the oxidation of LDL by SlN-I was not sensitive to the addition of exogenous lipid hydroperoxide.

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Loss of α‐tocopherol upon exposure to nitric oxide or the sydnonimine SIN‐1

Cited by 82 publications

References 29 publications

Suppression of nitric oxide toxicity in islet cells by α‐tocopherol

Suppression of nitric oxide toxicity in islet cells by α‐tocopherol

Dietary antioxidant supplementation reduces lipid peroxidation but impairs vascular function in small mesenteric arteries of the streptozotocin-diabetic rat

The oxidation of α‐tocopherol in human low‐density lipoprotein by the simultaneous generation of superoxide and nitric oxide

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