Selective kappa-opioid receptor (KOR) agonists are considered a promising group of substances for developing opioid analgesics characterised with an original mechanism of action without the risk of respiratory depression and drug addiction. Previous studies identified a fluorophenyl derivative of imidazo[1,2-a]benzimidazole (RU-1205) with a KOR-based mechanism of analgesic action established in in vitro and in vivo experiments.The aim of the study was to assess the effect of 9-(2-morpholinoethyl)-2-(4-fluorophenyl)imidazo[1,2-a]benzimidazole dihydrochloride on the level of DNA damage in rats after a single subcutaneous injection.Materials and methods. The study was conducted in adult white outbred laboratory rats of both sexes. DNA damage was estimated using the comet assay. The study involved a single subcutaneous injection of an aqueous solution of RU-1205 in three doses: 1, 10, and 100 mg/kg. The authors used intraperitoneal methyl methanesulfonate (40 mg per kg of animal body weight) as a positive control and 0.9% NaCl  (100 μL per 100 g of animal body weight) as a negative control.Results. A single subcutaneous injection of RU-1205 to rats did not produce a significant dose-dependent increase in % tail DNA when compared with the state of   the corresponding organ/tissue cell genome in negative control animals after normal saline administration at the same time points. In the negative control groups, % tail DNA in cells of various organs/tissues ranged from 1.83% to 3.82% (median values [25–75%]). On the contrary, the administration of 40 mg/kg of genotoxic methyl methanesulfonate led to an increase in damaged DNA in all studied organs and tissues when compared with negative control animals.Conclusions. The study of 9-(2-morpholinoethyl)-2-(4-fluorophenyl)imidazo[1,2-a] benzimidazole dihydrochloride genotoxicity demonstrated that a single subcutaneous injection of 1, 10, or 100 mg/kg of RU-1205 to rats did not damage the cell genome of the studied organs.

In the framework of the study, the degree of defragmentation of DNA by the DNA-comet method is evaluated when exposed to the cell culture of hydrogen peroxide (H2O2), and an in vitro model is developed to evaluate the antioxidant activity of new pharmacological agents. The results of working with cell lines show that the percentage of damage to the genetic material of cells of intact samples does not greatly vary from the method of removing the cellular monolayer from the culture plastic. Concerning the effect of H2O2 as an inducer of oxidative stress on DNA cell damage, the optimal level of DNA defragmentation has been modeled for subsequent studies of the protective action of antioxidants.

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In this investigation used the method of serum starvation to synchronize the culture of Vero cells at the G0/G1. The synchronization efficiency was 40 %, the elongation coefficient was 1,657 ± 0,26, and the flattening coefficient was 1,399 ± 0,123. Cell synchronization provides to get a population of cells that respond identically in a narrow dose range and are more resistant to toxic effects.