EFFECT OF CYCLOSPORINE-A AND TRIFLUOPERAZINE ON RAT-LIVER MITOCHONDRIA SWELLING AND LIPID-PEROXIDATION

The effect of cyclosporin A (CsA) or trifluoperazine (TFP) on lipid pe roxidation and mitochondrial swelling was determined using liver mitoc hondria incubated with 30 muM Ca2+ and 250 muM t-butylhydroperoxide or 5 mM inorganic phosphate (Pi). Lipid peroxidation was not modified by either 1 muM CsA or 40 muM TFP. These compounds presented a distinct effect on mitochondrial permeability. Under oxidative conditions, CsA only showed a transient protective effect whereas TFP completely inhib ited mitochondrial swelling. Conversely, CsA was very efficient when C a2+ and Pi were used, a condition under which TFP was unable to preven t the swelling. These data are consistent with our previous results (M .F. Nepomuceno, D.V. Macedo and L. Pereira-da-Silva (1991). Brazilian Journal of Medical and Biological Research, 24:833-836) showing that l ipid peroxidation is one among other different components of the perme abilization process. The data suggest that lipid peroxidation is indep endent of swelling, occurring later than swelling, presumably when the mitochondrial reductant systems are depleted. The differential effect s of CsA and TFP suggest that these compounds can be used as specific probes in the elucidation of the two distinct mechanisms responsible f or mitochondrial swelling.