Characteristics of proliferation and apoptosis of hepatocytes after administration of ascorbic acid in a model of radiation hepatitis

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Abstract

BACKGROUND: Radiation hepatitis with the development of radiation-induced acute liver failure is considered one of the most serious complications of radiotherapy for malignant neoplasms of the liver, abdominal organs, or whole body irradiation. However, the exact mechanisms of radiation-induced liver cell death have not been fully elucidated, and therefore the study of changes in the proliferative-apoptotic ratio in liver structures remains relevant, and pre-irradiation administration of ascorbic acid can potentially protect them from the effects of electron irradiation.

AIM: Assessment of proliferation and apoptosis of hepatocytes after administration of ascorbic acid in a model of radiation hepatitis.

MATERIALS AND METHODS: Wistar rats (Rattus Wistar; n=40) were divided into four experimental groups: I — control (n=10); II (n=10) — fractional irradiation with electrons in a total irradiation dose of 30 Gy; III (n=10) — administration of ascorbic acid before electron irradiation; IV (n=10) — administration of ascorbic acid. Animals of all groups were removed from the experiment a week after the last fraction. Morphological and immunohistochemical (with antibodies to Ki-67 and caspase-3) studies were carried out.

RESULTS: A week after electron irradiation, a sharp decrease in the proportion of Ki-67-positive hepatocytes in combination with an increase in immunolabeling with antibodies to caspase-3 was observed in group II. During the administration of ascorbic acid in group III, less pronounced depth and range of liver damage was noted, confirmed by morphological and immunohistochemical methods (less pronounced decrease in the level of Ki-67 expression and an increase in the proportion of caspase-positive hepatocytes compared to the control) methods.

CONCLUSIONS: An immunohistochemical study of proliferation and apoptosis of hepatocytes revealed that a week after fractional electron irradiation in total irradiation dose 30 Gy, there is a decrease in mitotic activity and an increase in cell death, and pre-irradiation administration of ascorbic acid helped level out the detected changes, which indicates its protective effect.

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About the authors

Grigory A. Demyashkin

National Medical Research Radiological Centre; Peoples' Friendship University of Russia named after Patrice Lumumba; I.M. Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: dr.dga@mail.ru
ORCID iD: 0000-0001-8447-2600
SPIN-code: 5157-0177

MD, Dr. Sci. (Medicine)

Russian Federation, Moscow; Moscow; Moscow

Dmitry A. Atyakshin

Peoples' Friendship University of Russia named after Patrice Lumumba

Email: atyakshin-da@rudn.ru
ORCID iD: 0000-0002-8347-4556
SPIN-code: 3830-8152
Russian Federation, Moscow

Vladislav A. Yakimenko

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: Yavladislav87@gmail.com
ORCID iD: 0000-0003-2308-6313
SPIN-code: 3572-7563
Russian Federation, Moscow

Dali I. Ugurchieva

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: daliyagurchieva@gmail.com
ORCID iD: 0009-0004-7308-8450
Russian Federation, Moscow

Matvey A. Vadyukhin

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: vma20@mail.ru
ORCID iD: 0000-0002-6235-1020
SPIN-code: 9485-7722
Russian Federation, Moscow

Alikhan A. Abuev

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: abuevv_06@mail.ru
ORCID iD: 0009-0001-9557-4909
Russian Federation, Moscow

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2. Fig. 1. Liver of control and experimental groups: top row — hematoxylin and eosin (H&E) staining, ×400; middle row — immunohistochemical picture with antibodies to Ki-67, ×400; bottom row — immunohistochemical picture with antibodies to caspase-3 (Cas-3), ×400. AA — ascorbic acid. Line — 50 µm. Asterisk indicates central vein, arrow indicates immunostained hepatocytes

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3. Fig. 2. Proliferation and apoptosis of hepatocytes in the control and experimental groups according to the results of immunohistochemistry with antibodies to Ki-67 and caspase-3. Data are presented as means (range); * statistically significant differences compared to the control in the “Irradiation” and “Irradiation + AA” groups; p <0.05. АА — ascorbic acid

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