Antimycin A and lipopolysaccharide cause the leakage of superoxide radicals from rat liver mitochondria.

Here we show that both Antimycin A, a respiratory chain inhibitor inducing apoptosis, and endotoxic shock, a syndrome accompanied by both necrosis and apoptosis, cause not only an increase but also the leakage of superoxide radicals (O(2)(-)) from rat heart mitochondria (RHM), while O(2)(-) generated in intact RHM do not escape from mitochondria. This was shown by a set of O(2)(-)-sensitive spin probes with varying hydrophobicity. The levels of O(2)(-) detected in intact RHM gradually increase as the hydrophobicity of spin probes increases and were not sensitive to superoxide dismutase (SOD) added to the incubation medium. Both Antimycin A and endotoxic shock elevated O(2)(-) levels. Elevated O(2)(-) levels became sensitive to SOD but in a different manner. The determination of O(2)(-) with water-soluble PPH was fully sensitive to SOD, while the determination of O(2)(-) with the more hydrophobic CMH and CPH was only partially sensitive to SOD, suggesting the release of a portion of O(2)(*-) into the surrounding medium.