Features of proliferation and apoptosis of pancreatic cells after administration of n-acetylcysteine in a model of acute post-radiation pancreatitis

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Abstract

Studies of post-radiation lesions of the pancreas after irradiation with charged particles (electrons, protons) are few, however, electron therapy is one of the promising methods in radiobiology and can be used to model post-radiation pancreatitis. The mechanisms of radiation-induced damage to the pancreas have not been fully elucidated, and studies of the life cycle of pancreatic cells after electron irradiation are rare. In addition, it is interesting to study changes in the proliferative-apoptotic balance of pancreatic structures protected from the effects of ionizing radiation by the introduction of N-acetylcysteine (NAC).

Material and methods. Wistar rats (n=50) were divided into four experimental groups: I – control (n=10); II (n=20) – fractional local irradiation with electrons; III (n=20) – administration of NAC before electron irradiation; IV (n=10) – administration of NAC. Animals of all groups (I – IV) were removed from the experiment a week after the last fraction. Fragments of pancreatic cancer were prepared for morphological and immunohistochemical tests (with antibodies to Ki-67 and caspase-8). Data are expressed as mean ± standard deviation. In the case of a normal distribution, the Student’s t-test was used, in the case of a non-normal distribution, the Mann–Whitney U-test was used.

Results. In group II, a week after fractional irradiation with electrons at a total dose of 25 Gy, an increase in the proportion of Ki-67-immunopositive cells and a decrease in the number of caspase-8-stained cells of pancreatic islets were found. Pre-irradiation administration of NAC reduced the degree of radiation damage to the pancreas, and staining parameters with antibodies to Ki-67 and caspase-8 were almost close to control values.

Conclusion. An immunohistochemical study of the pancreas revealed that local irradiation with electrons in summary dose 25 Gy after a week leads to a shift in the proliferative-apoptotic balance towards the death of pancreatic cells, which is partially restored with pre-irradiation administration of NAC, which indicates its protective effect.

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About the authors

Grigory A. Demyashkin

First Moscow State Medical University named after I.M. Sechenov (Sechenov University) Ministry of Health of the Russian Federation; Peoples’ Friendship University of Russia named after Patrice Lumumba

Author for correspondence.
Email: dr.dga@mail.ru
ORCID iD: 0000-0001-8447-2600

Doctor of Medical Sciences, Professor, Director of the Scientific and Educational Resource Center “Innovative Technologies of Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis”

Russian Federation, st. Trubetskaya, 8/2, Moscow, 119991; st. Miklouho-Maklaya, 6, Moscow, 117198

Dmitry A. Atyakshin

Peoples’ Friendship University of Russia named after Patrice Lumumba

Email: atyakshin-da@rudn.ru
ORCID iD: 0000-0002-8347-4556

Doctor of Medical Sciences, Head of the Laboratory of Histology and Immunohistochemistry of the Institute of Translational Medicine and Biotechnology, leading researcher at the Scientific and Educational Resource Center «Innovative technologies of immunophenotyping, digital spatial profiling and ultrastructural analysis»

Russian Federation, st. Miklouho-Maklaya, 6, Moscow, 117198

Dali I. Ugurchieva

Peoples’ Friendship University of Russia named after Patrice Lumumba

Email: daliyagurchieva@gmail.com
ORCID iD: 0009-0004-7308-8450

graduate student of the Scientific and Educational Resource Center “Innovative Technologies of Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis”

Russian Federation, st. Miklouho-Maklaya, 6, Moscow, 117198

Vladislav A. Yakimenko

First Moscow State Medical University named after I.M. Sechenov (Sechenov University) Ministry of Health of the Russian Federation

Email: Yavladislav87@gmail.com
ORCID iD: 0000-0003-2308-6313

graduate student at the Institute of Translational Medicine and Biotechnology

Russian Federation, st. Trubetskaya, 8/2, Moscow, 119991

Matvey A. Vadyukhin

First Moscow State Medical University named after I.M. Sechenov (Sechenov University) Ministry of Health of the Russian Federation

Email: vma20@mail.ru
ORCID iD: 0000-0002-6235-1020

student of the Institute of Clinical Medicine named after N.V. Sklifosovsky

Russian Federation, st. Trubetskaya, 8/2, Moscow, 119991

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Supplementary files

Supplementary Files
Action
1. JATS XML
2. Pancreas of control and experimental groups. Top row – hematoxylin and eosin staining; ×200. Middle row – immunohistochemical picture with antibodies to Ki-67; ×400. Bottom row – immunohistochemical picture with antibodies to caspase-8 (Cas 8); ×400

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