The role of free radicals in myocardial cell injury.
Free radicals can affect lipids of membranes by initiating peroxidation. Since alterations in membrane fluidity can modulate membrane functions including ion permeability, the effects of free radicals on the intracellular Ca2+ level ([Ca2+]i) and membrane fluidity were studied. Human erythrocytes were spin-labeled with 5-DSA and the membrane fluidity was quantified by ESR during application of oxygen-derived free radicals. The morphology was observed by the scanning electron microscopy. The effects of H2O2 on [Ca2+]i were studied using single guinea pig ventricular myocytes and fura-2 AM. Superoxide and H2O2 (10(-3) and 10(-4) M) induced a decrease in membrane fluidity and morphological changes of erythrocytes. [Ca2+]i significantly increased from the control value (53 +/- 4 nmol/litre) to 110 +/- 29 nmol/litre when the cells were shortened, and to 130 +/- 26 nmol/litre before cells became rounded. This study showed that [Ca2+]i was significantly increased by oxygen-derived free radicals, possibly by lipid peroxidation of the cell membrane. During perfusion with H2O2 however, the increase in [Ca2+]i was not pronounced. Therefore, we suspect that the mechanism of cell injury due to free radicals may be a combination of direct cell membrane injury and Ca2+ overload rather than intracellular Ca2+ overload.
Kobayashi
A
A
Third Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
Hayashi
H
H
Watanabe
H
H
Miyata
H
H
Kurata
C
C
Yamazaki
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016166:Free Radical Scavengers; D005609:Free Radicals; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010100:Oxygen / Q000502:physiology*
D016166:Free Radical Scavengers; D005609:Free Radicals; D006861:Hydrogen Peroxide; D010100:Oxygen; D002118:Calcium