Renal proliferation and apoptosis against ascorbic acid administration in a model of acute radiation nephropathy

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Abstract

BACKGROUND: Radiation exposure, an integral part of the treatment of malignant neoplasms, is associated with a risk of radiation nephropathy because of the high radiosensitivity of the kidneys. The analysis of renal tissue proliferation and apoptosis is important to understand the mechanisms of radiation damage and develop treatment strategies.

AIM: To evaluate endothelial proliferation and apoptosis of vascular tubules and nephrocytes during preradiation administration of ascorbic acid in a model of radiation nephropathy.

MATERIALS AND METHODS: Wistar rats (n=90) were divided into groups: I, control (n=15); II, irradiation, 2 Gy dose (n=15); III, irradiation, 8 Gy dose (n=15); IV, irradiation, 2 Gy dose + ascorbic acid, intraperitoneal injection at 50 mg/kg (n=15); V, irradiation, 8 Gy dose + ascorbic acid, intraperitoneal injection at 50 mg/kg (n=15); VI, ascorbic acid, intraperitoneal injection at 50 mg/kg (n=15). Kidney slides were stained with hematoxylin and eosin. In addition, immunohistochemical evaluation of the expression levels of Ki-67- and Cas-3-positive cells was performed.

RESULTS: The histological study showed that preradiation administration of ascorbic acid (intraperitoneal injection of 50 mg/kg) in the acute radiation nephropathy model induced by local irradiation with electrons at 2 and 8 Gy contributed to the statistical reduction of pathomorphologic changes. According to the results of immunohistochemical evaluation of proliferation and apoptosis, distribution of Ki-67- and Cas-3-positive cells in the tubules, epitheliocytes of proximal and distal tubules of nephrons in mono-irradiation groups revealed the activation of the terminal stage of cell death, which correlated with the electron irradiation dose. Moreover, in the experimental groups with preirradiation administration of ascorbic acid, a significant decrease in the intensity of apoptosis was recorded.

CONCLUSION: Preradiation administration of ascorbic acid reduces the strength of radiation-induced kidney damage and the effect of electron irradiation on the life cycle of tubular cells and epitheliocytes of nephron tubules while increasing the effectiveness of the antioxidant defense.

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About the authors

Grigory A. Demyashkin

The First Sechenov Moscow State Medical University (Sechenov University); National Medical Research Radiological Center

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

Zhanna E. Uruskhanova

The First Sechenov Moscow State Medical University (Sechenov University)

Email: jey.149@yandex.ru
ORCID iD: 0009-0009-2291-3680
Russian Federation, Moscow

Sergey N. Koryakin

National Medical Research Radiological Center

Email: korsernic@mail.ru
ORCID iD: 0000-0003-0128-4538
SPIN-code: 8153-5789

Cand. Sci. (Biology)

 
Russian Federation, Moscow

Mikhail A. Parshenkov

The First Sechenov Moscow State Medical University (Sechenov University)

Email: misjakj@gmail.com
ORCID iD: 0009-0004-7170-8783
Russian Federation, Moscow

Tatiana K. Dubovaya

The Russian National Research Medical University named after N.I. Pirogov

Email: gusvbr@mail.ru
ORCID iD: 0000-0001-7936-180X
SPIN-code: 4254-6082

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow

Galina M. Rodionova

The First Sechenov Moscow State Medical University (Sechenov University)

Email: rodionovagalinam@mail.ru
ORCID iD: 0000-0002-0536-9590
SPIN-code: 5657-9984

Cand. Sci. (Pharmacy), Assistant Professor

Russian Federation, Moscow

Vladimir I. Shchekin

The First Sechenov Moscow State Medical University (Sechenov University)

Email: dr.shchekin@mail.ru
ORCID iD: 0000-0003-3763-7454
SPIN-code: 3664-8044
Russian Federation, Moscow

Yuliya V. Ivchenko

The First Sechenov Moscow State Medical University (Sechenov University)

Email: ivchenko_yu_v@student.sechenov.ru
ORCID iD: 0000-0003-1336-7277
Russian Federation, Moscow

Olga V. Ionova

The First Sechenov Moscow State Medical University (Sechenov University)

Email: olgaionova99@mail.ru
ORCID iD: 0009-0007-9137-6597
Russian Federation, Moscow

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2. Fig. 1. Kidneys Wistar lab rats of control and experimental groups. Hematoxylin and eosin staining, ×200.

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3. Fig. 2. Kidneys Wistar lab rats of control and experimental groups. Immunohistochemical study with antibodies to Ki-67, staining with haematoxylin; ×400.

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4. Fig. 3. Kidneys Wistar lab rats of control and experimental groups. Groups are numbered according to the study design. * Comparison with control group (p <0.05). ** Comparison of group IV with group II (Single local dose 2 Gy + ascorbic acid and Single local dose 2 Gy; p <0.01). *** Comparison of group V with group III (Single local dose 8 Gy + ascorbic acid and Single local dose 8 Gy; p <0.01). Proportion of Ki-67-positive cells: a ― in the renal calf; b ― in proximal and distal tubules of nephrons; c ― in the tubules of the loop of Henle and collecting tubules.

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5. Fig. 4. Kidneys Wistar lab rats of control and experimental groups. Immunohistochemical study with antibodies to caspase-3, staining with haematoxylin; ×400.

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6. Fig. 5. Kidneys Wistar lab rats of control and experimental groups. Groups are numbered according to the study design. * Comparison with control group (p <0.05). ** Comparison of group IV with group II (Single local dose 2 Gy + ascorbic acid and Single local dose 2 Gy; p <0.01). *** Comparison of group V with group III (Single local dose 8 Gy + ascorbic acid and Single local dose 8 Gy; p <0.01). Proportion of caspase-3-positive cells: a ― in the renal calf; b ― in proximal and distal tubules of nephrons; c ― in the tubules of the loop of Henle and collecting tubules (p <0.001).

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