Abstract
Introduction. Radiotherapy carries a risk of liver damage: radiation-induced liver disease develops in 5 – 10% of cases after gamma-irradiation at 30 Gy, driven by oxidative stress and depletion of endogenous antioxidant defense. Existing radioprotectors, such as amifostine, are limited by a narrow therapeutic range; N-acetylcysteine, which replenishes the intracellular reduced glutathione pool, is therefore considered a promising protective substrate.
Aim: comparative analysis of structural and functional changes and proliferative-apoptotic ratio in hepatocytes after local electron irradiation and pre-irradiation administration of N-acetylcysteine.
Material and methods. Radiation-induced liver injury was modeled in 60 male Wistar rats (four experimental groups). During the first month, blood biochemistry parameters (transaminase, alkaline phosphatase, and bilirubin levels) and superoxide dismutase and malondialdehyde levels in liver tissue homogenate were assessed. Histological and immunohistochemical analyses (including hepatocyte proliferation and apoptosis indices) were also performed, and the data were processed statistically.
Results. Irradiation caused a significant increase in transaminases, bilirubin and malondialdehyde and a decrease in superoxide dismutase, dystrophic and necrotic hepatocyte changes, sinusoidal dilation, Kupffer cell hyperplasia, decreased Ki-67 expression, and an increased proportion of Caspase 3-positive cells. Pre-irradiation N-acetylcysteine partially prevented these changes and promoted recovery of the studied parameters by day 30.
Conclusion. Pre-irradiation administration of N-acetylcysteine as a radioprotector reduces the degree of structural and functional changes and the level of cell death in the liver, inducing antiapoptotic and proregenerative mechanisms in the long-term period after local electron exposure.
Authors and affiliations
https://elibrary.ru/rgauga G.A. Demyashkin, M.A. Vadyukhin, V.I. Shchekin, D.V. Belokopytov
Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University
of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya str., 8, build. 2, Moscow, 119991, Russian Federation
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