Free radicals, myocytes and reperfusion injury

Turner, Jeremy; Rice‐Evans, Catherine; Davies, Michael J.; Newman, Emma

doi:10.1042/bst0181056

Cited by 21 publications

(11 citation statements)

References 33 publications

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“…High-molecular bodymass DFO conjugates do not cause hypotension, so that much larger amounts of the DFO conjugate could be administered [31]. However, it is important to realize that the DFO conjugate cannot chelate intracellular NPBI, and cannot reduce the formation of NPBIinduced intracellular free radicals [32][33][34][35] and is therefore less protective.…”

Section: Discussionmentioning

confidence: 99%

Effect of Deferoxamine on Post-Hypoxic-Ischemic Reperfusion Injury of the Newborn Lamb Heart

Shadid

Bel²,

Steendijk³

et al. 1999

Neonatology

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Post-hypoxic-ischemic (HI) reperfusion induces excess production of non-protein-bound iron (NPBI), leading to formation of the highly reactive hydroxyl radical. We investigated whether the iron-chelator deferoxamine (DFO) could reduce reperfusion injury and improve left ventricular (LV) function. We produced severe HI in 14 newborn lambs and measured pre-HI, upon reperfusion, 60 and 120 min after HI the following parameters: mean aortic blood pressure, total peripheral resistance, stroke volume (SV), ejection fraction (EF) and LV contractility (pre-HI, 60 and 120 min post-HI). These parameters were assessed by measuring LV pressure (tip manometer) and volume (conductance catheter), using inflow occlusion to obtain slope (E_es) and volume intercept of the end-systolic P-V relationship (V₁₀). We determined the antioxidative capacity, i.e. the ratio of ascorbic acid and dehydroascorbic acid (AA/DHAA) and malondialdehyde from coronary sinus blood at pre-HI and at 15, 60 and 120 min post-HI. Seven lambs received DFO (10 mg/kg i.v.) immediately after HI, 6 control lambs received a placebo. While neither E_es nor EF changed significantly in either group, the volume intercept V₁₀ in the DFO-treated group was significantly smaller (0.25 ± 0.03 vs. 0.70 ± 0.09, p < 0.05), whereas SV was larger (3.6 ± 0.6 vs. 2.2 ± 0.2 ml, p < 0.05) and the AA/DHAA ratio was significantly lower at 15 min post-HI (p < 0.05) providing evidence for HI damage and for the protective effect of DFO. In conclusion: post-HI treatment of the newborn lamb with DFO has a modifying effect on free radical-induced damage to the myocardium and protects myocardial performance.

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Section: Discussionmentioning

confidence: 99%

Effect of Deferoxamine on Post-Hypoxic-Ischemic Reperfusion Injury of the Newborn Lamb Heart

Shadid

Bel²,

Steendijk³

et al. 1999

Neonatology

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“…While the iron heme protein myoglobin (Mb) plays an essential role in oxygen storage and transport in mammalian muscle, it can also catalyze oxidations of organic molecules. − The active oxidants in catalytic cycles are oxidized forms of Mb, which can be formed by reacting metmyoglobin [MbFe III ] with hydrogen peroxide: − In eq 1, X−MbFe III represents metmyoglobin and • X−MbFe IV O is the ferrylmyoglobin radical. One oxidizing equivalent from H 2 O 2 is used at the iron center, and the other creates a free radical located on an amino acid residue (X), possibly tyrosine-103, on the surface of the protein. , …”

Section: Introductionmentioning

confidence: 99%

Electrochemical Generation and Reactions of Ferrylmyoglobins in Water and Microemulsions

Onuoha

Rusling

1997

J. Am. Chem. Soc.

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Ferrylmyoglobin species, which are active oxidant forms of the protein myoglobin, were obtained by electrochemical reduction of metmyoglobin [MbFe III ] in the presence of oxygen in aqueous neutral buffer and in microemulsions of oil, water, and cationic surfactant. Reduction of myoglobin at -0.4 V vs SCE catalyzed the reduction of oxygen to hydrogen peroxide at the electrode. Hydrogen peroxide oxidizes metmyoglobin in solution to give the radical ferrylmyoglobin • X-MbFe IV dO, which is known to decay rapidly to the non-radical MbFe IV dO. This complex reduction-oxidation process converted nearly all of the 30 µM myoglobin in a spectroelectrochemical cell to ferrylmyoglobins in 15 min in pH 7.3 buffer and in 18 min in microemulsions. Characteristic ferryl heme absorbance bands near 421, 548, and 584 nm were used to identify products. Confirmation of ferrylmyoglobins was provided by reductions to metmyoglobin with ascorbate and by myoglobin-mediated electrochemical epoxidation of styrene. Fiftyfold higher yields of styrene oxide and benzaldehyde were achieved in a microemulsion compared to electrochemical or chemical methods in pH 7.4 buffer. The electrochemical approach described may also prove useful for investigating active catalytic species of heme enzymes such as cytochrome P450.

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“…Previous work has shown that ruptured cardiac myocytes under oxidative stress generate free radicals, the identity of which can be assigned to ferry1 myoglobin species [1,2]. The activation of myoglobin by hydrogen peroxide to ferry1 myoglobin proceeds through the oxidation by two oxidising equivalents.…”

Section: Introductionmentioning

confidence: 99%

The modulation of ferryl myoglobin formation and its oxidative effects on low density lipoproteins by nitric oxide

Dee¹,

Rice‐Evans²,

Obeyesekera³

et al. 1991

FEBS Letters

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This study has investigated the interactions between nitric oxide and haem protein radicals. The results demonstrate that nitric oxide interacts with activated ferrylmyoglobin species with reduction to metmyoglobin, but the extent and duration of the reduction depends on the relative concentrations of nitric oxide and hydrogen peroxide. Ferry1 myoglobin has a much greater relative potential for oxidising polyunsaturated fatty acid side chains in low density lipoproteins than in cell membranes. The peroxidative response can be modulated by nitric oxide: ferry1 myoglobin-mediated peroxidation of LDL may be enhanced or suppressed by nitric oxide depending on the relative concentrations of NO and hydrogen peroxide.

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Free radicals, myocytes and reperfusion injury

Cited by 21 publications

References 33 publications

Effect of Deferoxamine on Post-Hypoxic-Ischemic Reperfusion Injury of the Newborn Lamb Heart

Effect of Deferoxamine on Post-Hypoxic-Ischemic Reperfusion Injury of the Newborn Lamb Heart

Electrochemical Generation and Reactions of Ferrylmyoglobins in Water and Microemulsions

The modulation of ferryl myoglobin formation and its oxidative effects on low density lipoproteins by nitric oxide

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