Assessment of the Cytotoxicity of Peptide Modifications of Doxorubicin on Tetrahymena pyriformis.

The cytotoxicity of doxorubicin (Dox) and its peptide modifications Z-Gly-Pro-Dox and Boc-Gly-Pro-Dox were studied. Tetrahymena pyriformis was used as a test system, which made it possible, due to the short life cycle and high reproduction rate of ciliates, to trace their response to the effects of toxicants over several generations. It was found that peptide modification of the Dox molecule markedly reduces its cytotoxic and cytostatic effect. The Z-Gly-Pro-Dox modification has less cytotoxic and cytostatic effect compared to Boc-Gly-Pro-Dox. When determining the ability of drugs (at a concentration of 100 µM) to prevent bacterial contamination of samples, it was shown that the smallest degree of overgrowth was recorded in the presence of Dox (OD600nm 81.1). Boc-Gly-Pro-Dox also had a bacteriostatic effect, though less pronounced (OD600nm 93.8). The degree of overgrowth in the presence of Z-Gly-Pro-Dox was close to that of distilled water. The results obtained on ciliates did not contradict the data obtained in similar studies on mice.

Haloperidol Reduces the Activity of Complement and Induces the Anti-Inflammatory Transformation of Peritoneal Macrophages in Rats.

It is known that psychotropic substances affect the immune system. Unfortunately, chronic antipsychotic administration causes side toxicological effects, associated with oxidative stress. The mechanisms of these effects are still unclear. We investigated the impact of sub-chronic administration of haloperidol (Hal) on parameters of innate immunity and related systems in healthy rats and compared them with Hal content. Hal administration (0.5 mg/kg, 3 weeks) resulted in two-fold decrease of the activity of the complement system and hemostasis. Hal content correlated with the activity of the complement (r = -0.71), phagocytic activity of peritoneal macrophages (r = 0.78), leukocyte elastase (r = -0.71) and glutathione-S-transferase activity (r = -0.67). Hal fully blocked in vitro PMA-induced iNOS expression in macrophages and changed their morphology to "anti-inflammatory" phenotype. The comparison of in vivo and in vitro data showed that Hal has a direct effect on phagocytic component of innate immunity and an indirect effect on leukocyte elastase and antioxidant enzymes. The results obtained in the present study indicated that Hal significantly affects homeostasis and causes a number of complex biological transformations. Graphical Abstract.