Chain-breaking antioxidants and ferriheme-bound drugs are synergistic inhibitors of erythrocyte membrane peroxidation.
Induced erythrocyte membrane peroxidation (EMP) is considered as an accurate model of reperfusion injuries and as such was used to investigate protective effects of various drugs. EMP was induced by an azo initiator and monitored by oxygen uptake. Both hydrophilic (ascorbic acid) and lipophilic (alpha-tocopherol, probucol, nicanartine) chain-breaking antioxidants as well as ferriheme-bound drugs (deferoxamine, chloroquine) inhibited EMP. When antioxidants and ferriheme-bound drugs were combined, synergistic effects were observed. It is proposed that ferriheme compounds which catalyse peroxide induced lipid peroxidation were blocked by deferoxamine and/or chloroquine. So these drugs inhibited at least partly the membrane peroxidation process and added their effects to the ones of chain-breaking antioxidants.
Dailly
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Laboratoire de Pharmacologie, Faculté de Médecine, Créteil Université Paris XII, France.
Urien
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Tillement
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JP
D000328:Adult; D000578:Amidines / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology; D002738:Chloroquine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D003676:Deferoxamine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D004357:Drug Synergism; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006427:Hemin / Q000378:metabolism*; D006801:Humans; D019787:Linoleic Acid / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010108:Oxyhemoglobins / Q000494:pharmacology; D011341:Probucol / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology
D000578:Amidines; D000975:Antioxidants; D005227:Fatty Acids; D008563:Membrane Lipids; D010108:Oxyhemoglobins; D011725:Pyridines; D014810:Vitamin E; C046728:2,2'-azobis(2-amidinopropane); D006427:Hemin; C100546:nicanartine; D002738:Chloroquine; D019787:Linoleic Acid; D003676:Deferoxamine; D011341:Probucol; D001205:Ascorbic Acid