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., E. Kmoníčková, L. Kameníková, S. Hynie, H. Farghali., and Obsahuje bibliografii
We analyzed the effect of FK 506 on the production of nitric oxide by macrophages. Isolated rat peritoneal macrophages were cultured for 24 h with or without lipopolysaccharide (LPS) (5 µg/ml) and in the absence or presence of FK 506 (0.1 and 1 µg/ml). The concentration of NO2- in culture supernatants was taken as a measure of nitric oxide production. FK 506 (0.1 and 1 µg/ml) reduced the LPS-induced increase of NO2- levels by 68 % and 81 %, respectively. The impact of cyclosporin A (CsA) was studied in order to compare their effects. CsA (0.1 and 1 µg/ml) decreased the levels of nitrites by 39 % and 69 %, respectively. The results obtained suggest that both immunosuppressive drugs exhibit a dose-dependent inhibitory effect on nitric oxide production and that FK 506 is a more potent agent than CsA in this respect., P. Střeštíková, B. Otová, M. Filipec, H. Farghali., and Obsahuje bibliografii
The proportion of proliferating erythroblasts, i.e. proerythroblasts, basophilic erythroblasts and polychromatophilic erythroblasts in blood islands of the chick embryo yolk sac, were counted during embryonic days 2-10. From day 2 when high amounts of erythroblasts signalized the onset of embryonic erythropoiesis, the percentage of less mature erythroid cells gradually decreased. Intraamniotic injection of cyclosporin A in doses 1.5 or 15.0 /rg per embryo on day 5 led to significant changes in the proportion of proliferating erythroblasts in the yolk sac blood islands. We speculate that these changes were caused initially by the release of the more mature cells into the circulation and later by a dose-dependent decrease in the number of stem cells. The estimation of proerythroblast percentage from all proliferating erythroblasts in the yolk sac blood islands may serve as a valuable indication of toxic damage in the late avian embryo.