Cyclosporin A modifies cytoplasmic calcium levels in isolated hepatocytes exposed to oxidative stress due to tert-butyl hydroperoxide

Within the framework of our studies on hypertension in various rat strains, we have examined the effect of cyclosporin A (CsA) on intracellular calciu m signaling under conditions of oxidative stress. For these preliminary exp eriments, we have chosen isolated hepatocytes of normotensive rats as a mod el system for the study of the role of intracellular calcium. We used tert- butyl hydroperoxide (t-BHP, 1 mmol.l(-1)) as an prooxidant agent. When comp ared to the controls, we found increased levels of cytosolic free calcium c oncentration (Ca-i(2+)) during 120 min incubation. The preincubation of hep atocytes with CsA in the concentration of 0.5 mu mol.l(-1) did not change t he physiological level of cytosolic calcium. However, a dual action of CsA on elevated Ca-i(2+) was observed during oxidative injury of hepatocytes: w hile in the first period of incubation CsA increased Ca-i(2+), CsA reduced the effect of t-BHP on Ca-i(2+) during the next period of incubation. This indicates the ability of CsA to modify oxidative stress, but further studie s are necessary to explain these findings.