The formation of free radicals by cardiac myocytes under oxidative stress and the effects of electron-donating drugs.
The interaction of myoglobin with H2O2 leads via a two-electron oxidation process to the formation of ferryl myoglobin. Metmyoglobin is more readily activated than oxymyoglobin to the ferryl states, which are capable of inducing peroxidative damage to membranes. E.p.r. and optical spectroscopic studies show that the thiol-containing compounds N-(2-mercaptopropionyl) glycine and N-acetylcysteine and the trihydroxamate desferrioxamine attenuate these processes by reducing the ferryl myoglobin species to metmyoglobin, with the formation of thiyl radicals and the desferrioxamine nitroxide radical respectively. Biochemical investigations of the potential for myoglobin in ruptured myocytes to be involved in radical generation, when under oxidative stress, and of the nature of the resulting species, were also undertaken. E.p.r. spectroscopic studies revealed the formation of a radical species which is capable of inducing membrane lipid peroxidation. The interaction of the thiol compounds and desferrioxamine with components of myocardial tissue under these conditions results in the generation of thiol-derived radical species and the desferrioxamine nitroxide radical respectively. These data, along with those obtained using optical spectrocopy, support the assignment of the identity of the radical species generated from the myocytes as the ferryl myoglobin radical.
Turner
J J
JJ
Department of Biochemistry, Royal Free Hospital School of Medicine, London, U.K.
Rice-Evans
C A
CA
Davies
M J
MJ
Newman
E S
ES
D000111:Acetylcysteine / Q000737:chemistry; D000818:Animals; D003676:Deferoxamine / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism; D008786:Metmyoglobin / Q000737:chemistry*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D008625:Tiopronin / Q000737:chemistry
D005609:Free Radicals; D008054:Lipid Peroxides; D010545:Peroxides; D008786:Metmyoglobin; D008625:Tiopronin; D003676:Deferoxamine; D000111:Acetylcysteine