The mechanism of toxic action of hyperbaric oxygenation on the mitochondria of rat-heart cells

Abstract

Hyperbaric oxygenation of the whole animal was examined with respect to changes in mitochondria from heart cells. Accumulation of conjugated dienes, decrease of unsaturated fatty acids and changes in phospholipid pattern of the mitochondrial membrane indicate peroxidative damage of membrane lipids during oxygen stress. Hyperoxia induces increased activities of Superoxide dismutase, catalase and glutathione peroxidases, all enzymes protecting mitochondria from deleterious effects of reactive oxygen species. From the multiplicity of parameters related to pathophysiological effects of O₂ we inferred on increased formation rates of toxic oxygen species involving superoxide as the initial step in biological activation of O₂. The K_m for superoxide formation was 550 μM, ranging above physiological oxygen levels by a factor of 11. Thus, the mechanism by which hyperoxia might affect stimulation of superoxide formation is discussed on the basis of enhanced Michaelis-Menten kinetics due to elevated oxygen levels in the heart tissue. The onset of the membrane damage is the first event in hyperbaric O₂ toxicity. Despite a clear induction, activities of protecting enzymes seem to be ‘swamped’ by raising oxygen concentration above normal.