In 1973, David Hearse published his famous 'oxygen paradox' paper in which he noted that reoxygenation of isolated rat hearts following anoxia resulted in abrupt killing of heart cells, as demonstrated by a massive release of cardiac enzymes [l]. The source of the injury was not identified, but among the possible mechanisms listed was the release of free radicals. In mitochondria, molecular oxygen undergoes a four-electron reduction to water as the metabolic substrate is oxidized. Sequentially adding electrons to oxygen produces, in order, superoxide radical, hydrogen peroxide, hydroxyl radical and, finally, water. Radicals have unpaired electrons in their outer shell so they are potent oxidizing or reducing agents against any molecule they happen to contact, making them very toxic in biological systems.
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