Role of oxygen radicals in cardiac injury due to reoxygenation.
The ability of oxygen derived free radicals to induce irreversible cellular injuries during reoxygenation was studied on isolated potassium-arrested heart preparation. Enzymatic scavengers of hydrogen peroxide (H2O2) and superoxide anion (O-2), catalase and superoxide dismutase, were not effective in reversing the cardiac alterations induced by hypoxia. Cellular injuries induced by reoxygenation, 'Oxygen paradox', were partially prevented by scavengers of H2O2 (glutathione reduced form, catalase) and O-2 (superoxide dismutase). The 'oxygen paradox' was associated with a release of malonaldehyde. The inhibition of lipid peroxidation by alpha-tocopherol prevented the toxic effect of molecular oxygen on hypoxic hearts. The specific quenchers of singlet oxygen (histidine) and hydroxyl radical (mannitol) reduced the peroxidation of unsaturated lipids and the intensity of the 'oxygen paradox' phenomenon. The results indicate that in cardiac muscle (i) oxygen derived free radicals are important byproducts of abnormal oxidative metabolism present during the post hypoxic period; (ii) the 'oxygen paradox' phenomenon is related to the formation of lipid hydroperoxides leading to the cellular membrane disruption and to the irreversible alteration of cardiac integrity.
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000378:metabolism; D005609:Free Radicals; D005978:Glutathione / Q000494:pharmacology; D006639:Histidine / Q000494:pharmacology; D006878:Hydroxides; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D005609:Free Radicals; D006878:Hydroxides; D007773:Lactates; D008054:Lipid Peroxides; D013481:Superoxides; D014810:Vitamin E; D017665:Hydroxyl Radical; D008353:Mannitol; D006639:Histidine; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D002374:Catalase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D005978:Glutathione; D010100:Oxygen