Assessment of the DNA damage level in peripheral blood leukocytes of mice treated orally with Rapitalam in acute and therapeutic doses

Abstract

Rapitalam is a drug that is a modulator of the mglur4 receptor - a kind of metabotropic glutamate receptors. Into BelSU Clinical and Preclinical Studies Centre there was performed experimental research, which carried out the identification and quantitative assessment of alkali-labile sites and DNA strand breaks in leukocytes of peripheral blood of male mice treated with Rapitalam. The method is based on the assessment of the integrity of DNA in leukocytes of the whole blood of animals. Rapitalam was administered to animals orally according to 2 schemes: a single acute dose (413 mg/kg, which corresponds to 1/5 LD50 dose) and once daily in a therapeutic dose (3 mg/kg) for 4 days. For analysis we used peripheral blood of mice. As an indicator of DNA damage there was used the value of %TDNA. The results of this study established that the level of DNA damage of blood leukocytes (%TDNA) in the groups with acute dose of Rapitalam statistically significantly different from those values in control group of animals, indicating the presence of DNA-damaging activity of Rapitalam in the acute dose. Analysis of the level of DNA damage of blood leukocytes (%TDNA) in groups of animals treated with therapeutic dose of Rapitalam showed significant differences between animals treated with solvent (dimethyl sulfoxide) and animals treated with Rapitalam dissolved in DMSO. Conspicuous is the fact that there is observed a significant reduction in DNA damage in the therapeutic dose of Rapitalam as compared to the acute dose and the group receiving only the solvent. This suggests that Rapitalam in a therapeutic dose can influence on the processes of intracellular metabolism and acts as a protector.