An α-tocopherol analogue with antioxydant activity improves myocardial function during ischemia reperfusion in isolated working rat hearts

Abadie, Claire; Baouali, A. Ben; Maupoil, Véronique; Rochette, Luc

doi:10.1016/0891-5849(93)90061-x

Cited by 25 publications

(4 citation statements)

References 20 publications

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“…In most of these organs, the inhibition of postischemic tissue damage has been associated with the preservation of microvascular perfusion. This has best been demonstrated in hearts, where the improvement of postischemic coronary blood flow after experimental myocardial infarction correlated well with the reduction in infarct size (1,27,33,119). In rats, intramuscular administration of vitamin E preserved microvascular perfusion after experimental ligation of the left anterior descending coronary artery, as assessed by the number and diameter of India ink-perfused capillaries: at 15 days after reperfusion, capillary length and diameters were increased by 49% and 53% over controls, respectively, and infarct size was reduced by 37% (2).…”

Section: Ischemia-reperfusion Injurymentioning

confidence: 86%

“…Another important protective effect of vitamin E lies in its ability to preserve microvascular perfusion in experimental gastric (74) and spinal cord injury (120), after coronary occlusion (2), and after experimental renal (22) and myocardial ischemia-reperfusion injury (33,119). As a consequence of these diverse effects of vitamin E in ischemic and reperfused organs, vitamin E has been shown to reduce the ischemia-reperfusion-induced tissue damage in different organs, including liver (78,87), muscle (57), central nervous system (30,136), kidney (77,118), gastrointestinal tract (138), and the heart (1,5,6,48,88,119,128). In most of these organs, the inhibition of postischemic tissue damage has been associated with the preservation of microvascular perfusion.…”

Section: Ischemia-reperfusion Injurymentioning

confidence: 99%

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Vitamin E: Focus on Microcirculation

Lehr

VAJKOCZY

Menger³

1998

Microcirculation

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Note. Vitamin E is the generic term for all tocopherols and tocotrienols having qualitatively the biological activity of RRRalpha-tocopherol (previously known as d-alpha-tocopherol). Alpha-tocopherol has the highest biological activity. Other major forms include beta-and gamma-tocopherol and alphatocotrienol. All-rac-alpha-tocopherol (previously known as dlalpha-tocopherol) is the synthetic form of vitamin E. Vitamin E activity in clinical trials has often been expressed as IU (International Units). One IU = 1 mg all-rac-alpha-tocopherol acetate = 0.74 mg RRR-alpha-tocopheryl acetate = 0.67 mg .

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Section: Ischemia-reperfusion Injurymentioning

confidence: 86%

Section: Ischemia-reperfusion Injurymentioning

confidence: 99%

Vitamin E: Focus on Microcirculation

Lehr

VAJKOCZY

Menger³

1998

Microcirculation

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“…Synthetic vitamin E analogues have been produced as an alternative to tocopherol for cardiovascular therapy [33], [34], [35]. A major water-soluble metabolite of α-tocopherol with a structure similar to these analogues is 2,5,7,8-tetramethyl-2-(2′-carboxyethyl)-6-hydroxychroman (α-CEHC), which is normally detected in human blood and urine after vitamin E supplementation [36], [37].…”

Section: Introductionmentioning

confidence: 99%

Solid Phase Synthesis of Mitochondrial Triphenylphosphonium-Vitamin E Metabolite Using a Lysine Linker for Reversal of Oxidative Stress

2013

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Mitochondrial targeting of antioxidants has been an area of interest due to the mitochondria's role in producing and metabolizing reactive oxygen species. Antioxidants, especially vitamin E (α-tocopherol), have been conjugated to lipophilic cations to increase their mitochondrial targeting. Synthetic vitamin E analogues have also been produced as an alternative to α-tocopherol. In this paper, we investigated the mitochondrial targeting of a vitamin E metabolite, 2,5,7,8-tetramethyl-2-(2′-carboxyethyl)-6-hydroxychroman (α-CEHC), which is similar in structure to vitamin E analogues. We report a fast and efficient method to conjugate the water-soluble metabolite, α-CEHC, to triphenylphosphonium cation via a lysine linker using solid phase synthesis. The efficacy of the final product (MitoCEHC) to lower oxidative stress was tested in bovine aortic endothelial cells. In addition the ability of MitoCEHC to target the mitochondria was examined in type 2 diabetes db/db mice. The results showed mitochondrial accumulation in vivo and oxidative stress decrease in vitro.

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“…However, it is often associated with the occurrence of severe reperfusion arrhythmias [1], which can carry along patient death. These arrhythmias are connected with spikes of cytosolic calcium [2,3] and burst of oxygen free radicals [4–6]. Hence, one of the strategies to save the myocardial tissue without inducing cardiac death consists of re‐establishing the coronary perfusion in the ischemic area in the presence of an anti‐arrhythmic agent.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial basis of the anti‐arrhythmic action of lidocaine and modulation by the n‐6 to n‐3 PUFA ratio of cardiac phospholipids

Demaison

Moreau

Clauw

et al. 2012

Fundamemntal Clinical Pharma

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The aim of this study was to evaluate the involvement of mitochondria in the mechanism of the anti-arrhythmic lidocaine. Rats were fed with a diet containing either n-6 polyunsaturated fatty acids (PUFAs, SSO group) or an equimolecular mixture of n-3 and n-6 PUFAs (FO group) for 8 weeks. The hearts were perfused according to the working mode using a medium with or without lidocaine 5 μm. They were then subjected to local ischemia (20 min) and reperfusion (30 min). Dietary n-3 PUFAs triggered the expected decrease in the n-6/n-3 PUFA ratio of cardiac phospholipids. Reperfusing the ischemic area favored the incidence of severe arrhythmias. Lidocaine treatment abolished almost completely reperfusion arrhythmias in the FO group, but did not display anti-arrhythmic properties in the SSO group. As it was indicated by measurements of the mitochondrial function, lidocaine seemed to favor mitochondrial calcium retention in the FO group, which might prevent cytosolic calcium spikes and reperfusion arrhythmias. In the SSO group, the resistance to lidocaine was associated with an aggravation of cellular damages. The mitochondrial calcium retention capacities were saturated, and lidocaine was unable to increase them, making the drug inefficient in preventing reperfusion arrhythmias.

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An α-tocopherol analogue with antioxydant activity improves myocardial function during ischemia reperfusion in isolated working rat hearts

Cited by 25 publications

References 20 publications

Vitamin E: Focus on Microcirculation

Vitamin E: Focus on Microcirculation

Solid Phase Synthesis of Mitochondrial Triphenylphosphonium-Vitamin E Metabolite Using a Lysine Linker for Reversal of Oxidative Stress

Mitochondrial basis of the anti‐arrhythmic action of lidocaine and modulation by the n‐6 to n‐3 PUFA ratio of cardiac phospholipids

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