SHORT COMMUNICATION

Cyclosporin A Modifies Cytoplasmic Calcium Levels in Isolated Hepatocytes Exposed to Oxidative Stress Due to tert-Butyl Hydroperoxide

E. Kmoníčková, L. Kameníková, S. Hynie, H. Farghali

Received July 12, 1999
Accepted December 22, 1999

Summary
Within the framework of our studies on hypertension in various rat strains, we have examined the effect of cyclosporin A (CsA) on intracellular calcium signaling under conditions of oxidative stress. For these preliminary experiments, we have chosen isolated hepatocytes of normotensive rats as a model 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 compared to the controls, we found increased levels of cytosolic free calcium concentration (Ca²⁺_i) during 120 min incubation. The preincubation of hepatocytes with CsA in the concentration of 0.5 m mol.l^–1 did not change the physiological level of cytosolic calcium. However, a dual action of CsA on elevated Ca²⁺_i was observed during oxidative injury of hepatocytes: while in the first period of incubation CsA increased Ca²⁺_i, CsA reduced the effect of t-BHP on Ca²⁺_i during the next period of incubation. This indicates the ability of CsA to modify oxidative stress, but further studies are necessary to explain these findings.

Key words
Rat hepatocytes · Hypertension · Ca²⁺_i · Cyclosporin A

Reprint requests
E. Kmoníčková, Ph.D., Institute of Pharmacology, First Faculty of Medicine,, Charles University, Albertov 4, 128 00 Prague 4, Czech Republic. e-mail: ekmon@lfl.cuni.cz