Cell surface 'blebbing' is an early consequence of hypoxic and toxic injury to cells. A rise in cytosolic free Ca2+ has been suggested as the stimulus for bleb formation and the final common pathway to irreversible cell injury. Here, using digitized low-light video microscopy, we examine blebbing, cytosolic free Ca2+, mitochondrial membrane potential and loss of cell viability in individual cultured hepatocytes. Unexpectedly, we found that after 'chemical hypoxia' with cyanide and iodoacetate, cytosolic free Ca2+ does not change during bleb formation or before loss of cellular viability. Cell death was precipitated by a sudden breakdown of the plasma membrane permeability barrier, possibly caused by rupture of a cell surface bleb.

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Molecular oxygen, itself not very reactive, can be converted by photosensitization to electronically excited singlet states, and by partial reduction to the superoxide and hydroxyl free radicals and to hydrogen peroxide. The very considerable toxicity of oxygen, which is due primarily to the properties of these derivatives, is ordinarily overlooked because aerobes have evolved an elaborate system of defenses which is reasonably adequate under ambient conditions. This toxicity becomes all too apparent when these defenses are overwhelmed at elevated pO2 or through the action of compounds which increase the conversion of oxygen to its more reactive derivatives. We will here consider the threat posed by oxygen and the defenses which make aerobic life possible.

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