Metformin prolongs survival rate in mice and causes increased excretion of cell-free DNA in the urine of X-irradiated rats

Abstract

An antidiabetic drug metformin has anticarcinogenic and geroprotective effects and has been used in combination with radiation cancer therapy. The present work is devoted to the study of the effect of metformin on survival in mice, the frequency of micronuclei in mouse bone marrow cells and excretion of cell-free nuclear and mitochondrial DNA in the urine of X-ray-exposed rats. The survival rate and the frequency of micronuclei in mice and excretion of DNA into rat urine were determined after administration of the drug before and after irradiation of animals. The DNA content was measured by qRT-PCR. Metformin shows a radioprotective effect only when administered to mice after the radiation exposure. On the 11th day after irradiation, we observed 100% mortality in the control group; 78% of mice remained alive if metformin was given. Twenty percent of the mice in this group survived for 30 days after irradiation. Metformin has the same effect on the frequency of micronuclei; its reduction is observed, when the drug is administered to the mice after irradiation. Metformin promotes the excretion of nuclear and mitochondrial DNA with the urine of irradiated rats. The results show that metformin acts as a radiomitigation effector. Metformin promotes the active excretion of DNA of dying cells from the tissues of irradiated animals.

Keywords: Cell-free DNA in the urine; Metformin; Micronuclei; Survival rate; X-irradiation.