Защитные свойства соединения АИКАР in vivo при радиационном воздействии

Abstract

Purpose: To study the effect of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) on the survival rate of mice and proportion of polychromatophilic erythrocytes (PCE) in the bone marrow cells with micronuclei (MN), as well as post-irradiation urinary excretion of cell-free nuclear DNA (cf-nDNA) and mitochondrial DNA (cf-mtDNA) in rats. Material and methods: Male Balb/c mice aged 2 months and Fisher-344 male rats aged 3 months were used. To determine the survival rate of mice, X-irradiation was performed at a dose of 8 Gy, and to analysis the proportion of PCE in the bone marrow cells with MN, at a dose of 2 Gy. Rats were X-irradiated at a dose of 5 Gy. AICAR was administered to animals intraperitoneally at a dose of 400 mg/kg. The drug was administered 30 min before and 20 min after irradiation of the animals. The DNA content was measured by real-time PCR. Results: The results of the study showed that the introduction of AICAR causes a statistically significant increase in the survival rate of irradiated animals. The greatest effect was shown in the group of mice treated with AICAR 20 min after their irradiation at a lethal dose. The introduction of AICAR before irradiation reduces the proportion of PCE with MN by 30 %, and after irradiation ‒ by 70 %, in comparison to the control. AICAR promoted enhanced urinary excretion of cf-nDNA and cf-mtDNA fragments in rats after irradiation. Conclusion: The results show that AICAR acts as a radiomitigation effector and promotes active DNA excretion of damaged cell from animal tissues in the post-radiation period.