METFORMIN AS A MODIFIER OF THE OXIDATIVE STATUS OF PERIPHERAL BLOOD AND THE VIABILITY OF HUMAN LYMPHOCYTES UNDER THE INFLUENCE OF IONIZING RADIATION

Glavin O.A., Domina E.A., Mikhailenko V.M., Makovetska L.I., Druzhyna M.O., Hrinchenko O.O.

• R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine

Aime: to determine the metformin (MF) effect on the transmembrane potential of mitochondria (TMP), the total production of free radical compounds (FRC) and formation of superoxide anion radical (О²_.-) in peripheral blood lymphocytes (PBL) of relatively healthy people, proliferative potential and apoptotic death of this cells, and also on the balance of pro- and antioxidant processes (PAP), the intensity of lipid peroxidation in the blood depending on the concentration of MF and irradiation dose. Object and methods: the study used peripheral blood samples from 37 relatively healthy individuals aged 22 to 58 years (18 women and 19 men). MF solution was added at final concentrations of 2 and 20 mM one hour before x-ray irradiation of blood in the dose range of 0,5 to 3,0 Gy. Using conventional methods ware determined the concentration of malondialdehyde (MDA), and PAP in the blood, as well as FRC, formation of superoxide anion radical (О²_.-), TMP, proliferative potential and apoptosis in PBL. Results: changes in the (О²_.-) production in the PBL and the content of MDA in blood plasma suggest the antioxidant effect of MF, which was more pronounced at its concentration of 2 mM and test irradiation of blood at doses of 1.0 and 2.0 Gy. Insignificant changes of PAP in the blood and the formation of FRC and TMP in the PBL were observed; also at MF concentration of 2 mM a tendency to decrease PAP and increase TMP was observed. MF increased the level of PBL apoptotic death and reduced their proliferative potential. This effect was observed both in the absence and after test irradiation of blood in the dose ranges of 0.5 to 3.0 Gy. Conclusions: the data obtained in the in vitro system indicate the possibility of using MF as a modifier of free radical processes, which causes a shift towards antioxidant reactions, including irradiation in the dose range of 0.5–3.0 Gy. MF in doses of 2 and 20 mM in vitro reduces proliferative potential of PBL and activates their apoptosis.