CYCLOSPORINE-A PROTECTS HEPATOCYTES SUBJECTED TO HIGH CA-2+ AND OXIDATIVE STRESS

Hepatocytes incubated with 0.8 mM t-butylhydroperoxide are protected by cyclosporin A when the medium Ca2+ concentration is 10 mM, but not when it is 2.5 mM. The highest Ca2+ level is associated with an inhibition of t-butylhydroperoxide-dependent malondialdehyde accumulation and with mitochondrial Ca2+ loading within the cells. These findings are new evidence that t-butylhydroperoxide can kill cells by peroxidation-dependent and -independent mechanisms, and suggest that the mitochondrial permeability transition and the resultant de-energization are components of the peroxidation-independent mechanism. Cyclosporin A may have considerable utility for the protection of cells subjected to oxidative stress.