The Role of Immunomodulator Betaleukin in Recovery of Hepatocytic Ploidy Profile in Delayed Terms after Irradiation
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Bulletin of Experimental Biology and Medicine, Vol. 169, No. 4, August, 2020
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MICROBIOLOGY AND IMMUNOLOGY The Role of Immunomodulator Betaleukin in Recovery of Hepatocytic Ploidy Profile in Delayed Terms after Irradiation L. P. Sycheva and L. M. Rozhdestvenskii
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 4, pp. 444-448, April, 2020 Original article submitted October 17, 2019 We studied the radioprotective effect of betaleukin administered to (CBA×C57Bl/6)F1 mice in single doses of 50 and 3 µg/kg 2 and 22 h, respectively, prior to long-term (21 h) wholebody low-intensity (10 mGy/min) γ-radiation (137Сs; total dose 12.65 Gy). Hepatocyte ploidy, a biomarker of metabolic disorders of the liver, was evaluated, and nuclearity and ploidy indices were calculated. In 10 months after irradiation, a significant decrease in the ploidy index was revealed in the group of irradiated mice, while in animal receiving 3 or 50 µg/kg betaleukin, this parameter did not differ and even surpassed the control level, respectively. Thus, in vivo assessment of hepatocytic ploidy profile in mice revealed negative delayed effects of γ-irradiation in a dose of 12.65 Gy and a protective effect a single injection of immunomodulator betaleukin. Key Words: γ-radiation; betaleukin; hepatocytes; ploidy index
Betaleukin, a human recombinant IL-1β, is a unique drug identical to the natural prototype by its physical, chemical, and biological properties [6]. This proinflammatory cytokine plays a key role in reactions of innate immunity where it regulates more than 50 molecular processes during acute phase of inflammation [7]. Betaleukin was approved for clinical use as an immunostimulator in secondary immunodeficiency states; now it is widely used in the treatment of various diseases [7] and recommended as a radiomodifier and radiotherapeutic agent [3]. Remembering that lowpower prolonged radiation exposures as well as the fractional local irradiation of tumors are harmful not due to their immediate effects (acute radiation sickness), but delayed consequences (cancer and fibrosis), A. I. Burnazyan State Research Centre Federal Medical Biophysical Center, Federal Medical Biological Agency, Moscow, Russia. Address for correspondence: [email protected]. L. P. Sycheva
of particular importance is the use of long-term radiomodifiers [4]. One of few preparations with this kind is betaleukin. However, the delayed effects of this drug as a radiomodifier remain little studied. At present, there is a growing interest to changes in hepatocytic ploidy related probably to high incidence of non-alcoholic fatty liver disease tending to develop into steatohepatitis viewed as a risk factor of hepatocellular carcinomas where ploidy is an important parameter [8]. No less important is the fact that intensive development of molecular biology revealed signaling pathways that control the cell cycle processes including the balance between mitosis, endomitosis, and endoreplication [12]. Now, the indices of hepatocyte ploidy are viewed a
