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 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 x 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 micromol x 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.
Kmonícková
E
E
Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czech Republic. ekmon@lfl.cuni.cz
Kameníková
L
L
Hynie
S
S
Farghali
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020122:tert-Butylhydroperoxide; D002118:Calcium