tBHP induced in vitro swelling of rat liver mitochondria

Tert-butyl hydroperoxide induced swelling of freshly isolated rat liver mitochondria was inhibited by butylated hydroxytoluene, butylated hydroxyanisole and alpha-tocopherol by acting at the initial phase. EDTA was more effective than EGTA in reducing the initial swelling and so were desferal and bipyrridyl. Spermine, an allosteric activator of calcium uptake, enhanced swelling whereas lanthanum and ruthenium red, the Ca2+ uniport blockers, reduced it. Inhibition of phospholipase A2 by dibucaine and Ca2+ activated proteases by antipain and leupeptin also reduced t-BHP induced swelling. The data indicate that peroxidative mitochondrial swelling involves an iron mediated initial rapid phase and a subsequent calcium dependent propagation phase.