Effects of a novel low-molecular weight antioxidant on cardiac injury induced by hydrogen peroxide.
H290/51, an indenoindole derivative, is a novel low-molecular weight (287.8) inhibitor of lipid peroxidation. Its effect on cardiac injury induced by exogenous reactive oxygen intermediates (ROI) was investigated. ROI were generated by adding H2O2 (180 mu M) to the perfusate of isolated rat hearts (Langendorff model, n = 9) for 10 min. H2O2 reduced left ventricular developed pressure (LVDP = left ventricular systolic pressure -- left ventricular end-diastolic pressure) from 90 +/- 6 to a minimum of 25 +/- 2 mmHg (mean +/- SEM) after 10 min (p < 0.001), elevated left ventricular end-diastolic pressure (LVEDP) from 0 to 32 +/- 7 mmHg after 20 min (p < 0.0001), and increased coronary flow (CF). Lactate dehydrogenase (LDH) release in the coronary effluent and thiobarbituric acid-reactive substances (TBARS) in cardiac tissue increased (TBARS from 0.6 +/- 0.04 to 3.1 +/- 0.4 nmol/g tissue after 10 min of H2O2 administration, p < 0.001). Addition of H290/51 (1 mu M, n = 12) from the start of H2O2 exposure, attenuated the H2O2-induced increase of LVEDP (9 +/- 3 mmHg at 20 min, p < 0.006) and reduced the release of LDH (p < 0.02 at 30 min). LVDP was not significantly influenced. The increase of TBARS was abolished by H290/51 (p < 0.001). In conclusion, H290/51 inhibited lipid peroxidation, and attenuated functional and biochemical injury induced by H2O2 exposure.
Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden.
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Nagy
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Sellei
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Valen
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Sjoquist
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Vaage
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; C088233:H290-51; D007211:Indoles; D017392:Thiobarbituric Acid Reactive Substances; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase