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2020 год. Совместная работа с НИЦ «Курчатовский институт» , г. Москва

Radioprotective effect of human lactoferrin against gamma-irradiation with sublethal dose

Marina Kopaeva1, Irina Alchinova3, Mikhail Nesterenko2, Anton Cherepov1, Mikhail Karganov3
1National Research Center Kurchatov Institute, Moscow, Russia;
2"Lactobio" LLC, Moscow, Russia;
3 Institute of General Pathology and Pathophysiolgy, Moscow, Russia;

E-mail: m.kopaeva@mail.ru

The pathogenic processes induced by ionizing radiation are currently being extensively researched. Radiation damage is basically due to DNA injury caused by the ionization effect of radiation. This process involves hyperoxidation by the free radicals produced. Lactoferrin (Lf) is a multifunctional protein of the transferrin family that is widely represented in various secretory fluids of mammals. Previously, it was shown the therapeutic effect of Lf purified from cow’s milk after single whole-body X-ray irradiation [Nishimura et al, 2014; Feng et al, 2018].

The aim of research was to investigate the effects of Lf in mice after acute gamma irradiation at a sublethal dose. Human Lf (hLf) was isolated from colostrum by preparative ion-exchange chromatography followed by purification with affinity heparin-sepharose sorbent. C57Вl/6 2-2,5 months old male mice were used for the experiments. Animals were randomly divided to experimental and control groups (three and four, respectively). Mice from experimental groups were treated with whole-body γ-radiation from a cobalt-60 (60Co) source at 7,5 Gy (at a dose rate of 0,6 Gy/min) followed by the intraperitoneal administration of hLf (4 mg/animal; «exp Lf» and «exp Lfx2» groups) or saline («exp» group). The control mice were sham irradiated. Mice from «exp Lfx2» and «cont Lfx2» groups were injected with hLf second time after 24 h. The assessment of the effect of Lf on the behavioral functions of irradiated animals (locomotor and research activity) was carried out using the "Open field" test on the 10th, 20th and 30th days. The survival rate at 30 d after irradiation was investigated. The body weights of the mice were measured every three days following irradiation.

Analyses of the data obtained from the "Open field" test revealed that 20 days after irradiation, the animals of the «exp Lf» and «exp Lfx2» groups did not differ from the control ones in the number of rearings. By day 30th, they were no different in terms of time spent in the central zone. While for the «exp» group, these parameters were significantly changed. The survival rate in Lf-treated mice 30 d after irradiation was 76% («exp Lfx2» group) and 71% («exp Lf» group), significantly higher than in mice treated with saline 29% («exp» group). Lf administration had a compensatory effect, which was manifested in an increase in the 30-day survival rate of irradiated animals and life expectancy, in a faster normalization of the dynamics of body weight changes. These findings suggest that Lf may inhibit radiation damage. Further studies are required to determine to clarify the value of Lf within the field of radiation protection.