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



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BACKGROUND: Radiation exposure, an integral part of the treatment of malignant neoplasms, carries a risk of radiation nephropathy due to the high radiosensitivity of the kidneys. The study of renal tissue proliferation and apoptosis is one of the keys to understanding the mechanisms of radiation damage and developing treatment strategies.

AIM: Evaluation of intrarenal regulation, proliferation, and apoptosis during pre-radiation administration of ascorbic acid.

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; dose 50 mg/kg) (n=15); V - irradiation, 8 Gy dose + ascorbic acid (intraperitoneal injection; dose 50 mg/kg) (n=15); VI - ascorbic acid (intraperitoneal injection; dose 50 mg/kg) (n=15). Kidney slides were stained with hematoxylin and eosin. In addition, immunohistochemical evaluation of the expression level of Ki-67- and Cas-3-positive cells was performed.

RESULTS: The histological study showed that pre-radiation administration of ascorbic acid (intraperitoneal injection; dose 50 mg/kg) in the model of acute radiation nephropathy induced by local irradiation with electrons at doses 2 Gy and 8 Gy contributed to 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 activation of the terminal stage of cell death, which correlated with the dose of electron irradiation. At the same time, in the experimental groups with pre-irradiation administration of ascorbic acid a statistically significant decrease in the intensity of apoptosis was recorded.

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

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RATIONALE
Radiation exposure is one of the methods of diagnostics and treatment of malignant neoplasms (MN) and is associated with a certain risk of early or late post-radiation complications [1-3].
It is known that kidneys are radiosensitive organs [4]. Thus, exposure to ionizing radiation leads to morphological changes in the vascular component, primarily in the endothelium of the tubules up to its detachment from the basal membrane. Therefore, radiation nephropathy is referred to thrombotic microangiopathy. In addition, there is damage to podocytes, nephron tubule epithelium and interstitial tissue. Post-radiation renal damage is manifested by proteinuria, hypertension and other symptoms [5, 6].
 The study of disruption of the life cycle of these cells plays a key role in assessing their compensatory response and regenerative potential [7]. After irradiation, there is a decrease in the proliferative activity of cells and their ability to regenerate, as signaling pathways responsible for ion transport are induced, leading to double-stranded DNA breaks [8]. When interacting with cellular water, reactive oxygen species such as hydrogen peroxide, superoxide and hydroxyl radical are formed, which negatively affect the genetic apparatus, cell membrane, proteins, etc. [9, 10]. [9, 10]. Cell death (apoptosis, necrosis, etc.) releases many damage associated molecules (DAMP) such as heat shock proteins, HMGB1, initiating immune responses that enhance anti-tumor mechanisms [11]. The regulation of the life cycle of endotheliocytes of the vascular bed and nephrocytes is closely related to the activation of proliferation protein Ki-67 and apoptotic enzyme caspase-3 [12].
Studies devoted to structural and functional changes in intact parts of the kidney, both during its direct irradiation with electrons and during electron therapy of neighboring organs are practically absent.
However, despite some progress in understanding the biology of the cell cycle, the issue of the development of radiation nephropathy requires more in-depth study, as well as the creation of experimental models to assess the proliferative-apoptotic balance. It is especially relevant after electron exposure as a promising method of modern radiobiology and radiation therapy of renal (intraoperative irradiation) and retroperitoneal organs.
In the specialized literature there is little data on the role of key regulators of proliferation and apoptosis in kidney structures against the background of administration of drugs with a protective effect, for example, ascorbic acid.
AIM.
To evaluate intrarenal regulation of proliferation and apoptosis during pre-radiation administration of ascorbic acid.
Objective: to determine the level of expression of proliferation (Ki-67) and apoptosis termination factors (caspase-3) in kidney structures against the background of ascorbic acid administration before a single local irradiation with electrons at single focal doses (FD) of 2 Gy and 8 Gy.
MATERIALS AND METHODS
In vivo animals were used as part of the experiment.  Male Wistar rats (220.3±10.6 g; 9-10 weeks old; n=90) were kept in a vivarium under controlled temperature (22°C) and light period (12L:12D) with free access to water and standard food. The rats were divided into six experimental groups:
- I - control (n=15); 
- II - experimental (n=15), animals were subjected to a single local irradiation with electrons at a single focal dose of 2 Gy; 
- III - experimental (n=15), animals were subjected to a single local irradiation with electrons at a single focal dose of 8 Gy;
- IV - experimental (n=15), before a single local irradiation with electrons at  a single focal dose of 2 Gy, the animals were administered ascorbic acid (intraperitoneal injection; dose 50 mg/kg);
- V - experimental group (n=15), before a single local irradiation with electrons at a single focal dose of 8 Gy the animals were administered ascorbic acid (intraperitoneal injection; dose 50 mg/kg);
- Group VI (n=15), animals were administered ascorbic acid (intraperitoneal injection; dose 50 mg/kg). 
All manipulations were performed according to the "International Recommendations for Biomedical Research Using Animals" (EEC, Strasbourg, 1985), "European Convention for the Protection of Vertebrate Animals Used for Experiments or Other Scientific Purposes" (EEC, Strasbourg, 1986) and Guidelines for Biomedical Research on the Care and Use of Laboratory Animals (ILAR, DELS), Rules of Laboratory Practice and the order of the Ministry of Health of the Russian Federation № 199n from 01.04.2016 "On Approval of the Rules of Laboratory Practice". 
Animals were irradiated on a pulsed electron gas pedal "NOVAC-11" (S.I.T. Sordina IORT Technologies S.P.A., Italy) in the Department of Radiation Biophysics of the A.F. Tsyb MRSC. The setup generates an electron beam with adjustable energy and collimation. The following parameters were chosen in the experiment: energy of 10 MeV, frequency of 9 Hz with collimation Ø 100 mm, which allowed to provide point and safe irradiation of the target zone of rat kidneys. This irradiation configuration was confirmed by dosimetric studies indicating electron penetration depths up to 50 mm, thus providing ideal conditions to achieve the required dose in the organ with minimal risk to surrounding tissues. 
The doses and irradiation mode (ROD 2 Gy and ROD 8 Gy; once) were chosen after preliminary approbation [13, 14].
Before irradiation, rats of experimental groups were sedated by a single injection of ketamine (50 mg/kg, i.p.) and xylazine (5 mg/kg, i.p.). 
Anesthetized animals were placed on the study table one at a time. The position was on the abdomen with paws spread apart to allow access to the study area. It was important that the lungs and heart were outside the irradiation zone, in the so-called radiation shadow. For maximum accuracy of irradiation, the tube was directed to the studied area so that its end was at a distance of no more than two millimeters from the skin, strictly perpendicular.
To ensure immobility of the animals during the procedure, special fixation devices were used. Additionally, the rest of the body, including bone marrow, was securely shielded to prevent unwanted radiation exposure. 
Animals of all groups (I-VI) were removed from the experiment by administration of high doses of anesthetic on the 7th day. After scheduled euthanasia, kidneys were removed from rats according to the design of the experiment. 
Histologic study. Kidney fragments were fixed in a solution of buffered formalin, after wiring ("Leica Biosystems", Germany) were cast into paraffin blocks, from which serial sections (3 μm thick) were prepared, dewaxed, dehydrated and stained with Mayer's hematoxylin and eosin.    
Considering that radiation nephropathy is manifested by lesions of tubules (thrombotic microangiopathy, collapse), nephron tubules and interstitial component, which lead to glomerulosclerosis and tubulointerstitial fibrosis, vacuolization, dystrophy, atrophy of tubules and nephron tubules, as well as inflammation and necrosis were evaluated by light microscopy (in 10 random fields of view at x200 magnification). The magnitude of lesions was calculated in points (from the lesion area): 0, absent; 1, mild (<25%); 2, moderate (25-50%); 3, severe (>50). Kruskal-Wallis test was used to test the statistical significance of differences between groups, p <0.05.
Immunohistochemical study. Paraffin sections with a thickness of 3 μm were used for immunohistochemical analysis. First, the sections were deparaffinized and then treated with 0.3% hydrogen peroxide solution in methanol for 30 minutes. All preparations were then autoclaved in citrate buffer for 20 minutes at pH 6.0, after which they were incubated with primary antibodies for 12 hours. Monoclonal antibodies to Ki-67 (ThermoFisher, Clone MM1), Caspase 3 (ThermoFisher, Clone 74T2) were used as primary antibodies, and universal antibodies (HiDef Detection™ HRP Polymer system, "Cell Marque", USA) were used as secondary antibodies. Cell nuclei were stained with Mayer's hematoxylin. The number of immunopositive cells was counted in 10 randomly selected fields of view at ×400 magnification (in %). 
Microscopic analysis was performed using a video microscopy system (Leica DM2000 microscope, Germany; Leica ICC50 HD camera).
Statistical analysis. All statistical analyses were performed using the computer program SPSS 12.0 for Windows (IBM Analytics, USA). All data are presented in the format of mean ± standard deviation (M±SD). Kolmogorov-Smirnov test was used for each sample separately. In case of normal distribution, Student's t-test was used. Differences between samples were considered statistically significant at a significance level of p<0.05 established before analysis.
RESULTS.
Normal histoarchitectonics was observed in the control group kidney samples: renal tubules, proximal and distal tubules of the nephron were located in the cortical substance, and other sections were located in the brain substance (Figure 1). A similar histologic pattern was found in the micropreparations of Group VI when ascorbic acid was mono-injected (Fig. 1)
In groups II and III (ROD 2 Gy and ROD 8 Gy) the following changes were noted: Bowman's capsule dilation, vacuolization, partial atrophy of nephron tubules, dissociation of macula densa cells, perivascular and paraglomerular edema, dystrophic changes, inflammatory reactions of interstitial tissue (Fig. 1).

At pre-radiation administration of ascorbic acid in groups IV and V, a decrease in the degree of pathomorphologic changes was observed (Fig. 1).
The magnitude of the lesions of the tubules (thrombotic microangiopathy, collapse), nephron tubules and interstitial component are presented in Table 1.
Immunohistochemical study. In the context of studying the mechanisms of life cycle regulation, the key factor of which is DNA synthesis, we evaluated proliferative activity - Ki-67, in the form of specific nuclear staining in endothelial cells of tubules, podocytes and nephrocytes, as well as epitheliocytes of proximal and distal nephrons (Fig. 2 A, B).
In kidney micropreparations of groups II and III we found differences in Ki-67 expression levels compared to the control group: insignificant decreases in positive cells, predominantly in the tubules (p<0.05) (Fig. 2 A, B). 
In the groups of pre-radiation administration of ascorbic acid, a slight increase in the number (in percent) of Ki-67-positive cells was observed relative to the mono-irradiation groups (ROD 2 Gy and ROD 8 Gy) (p<0.05) (Fig. 2 A, B).

There were no statistical differences in the distribution of Ki-67 positive cells (p<0.05) between the ascorbic acid mono-injection and control groups (Fig. 2 A, B) (Fig. 2 A, B).
  Immunohistochemical evaluation of the terminal stage of apoptosis revealed caspase-3-positive cells in the tubules and in the tubules of the nephron, the distribution of which varied between groups. The characteristic feature of these cells is the presence of partially brown cytoplasm and brown-yellow coloration of the nuclei (Fig. 3 A, B).
In groups II (ROD 2 Gy) and III (ROD 8 Gy), we found a significant increase in the number of cells stained with antibodies to caspase-3 relative to the groups, predominantly epitheliocytes, dilated or atrophied tubules of the nephron, with higher statistical significance in the distal nephron compared to the proximal nephron (p<0.05). When caspase-3 immunolabeled cells were distributed in renal tubules, the mean cell counts were 47±6 (ROD 2 Gy) and 72±6 (8 Gy) per 40 tubules (p<0.05) (Figure 3 A, B). 
In the groups receiving ascorbic acid before electron irradiation, a decrease in the level of nuclear staining in nephron tubule cells and renal tubules was recorded: the average number of cells was 34±5 (ROD 2 Gy + AK) and 45±3 (ROD 8 Gy + AK) per 40 tubules, which as a percentage was statistically lower than in groups II and III, respectively (p<0.01; p<0.001) (Fig. 3 A, B) (Fig. 3 A, B).  `

In group VI (ascorbic acid monotherapy) changes in caspase-3 expression were not statistically significant compared to the control group (p<0.05) (Fig. 3 A, B).
Thus, according to the results of immunohistochemical analysis of proliferation and apoptosis assessment - distribution of Ki-67- and Cas-3-positive cells in tubules, epitheliocytes of proximal and distal tubules of nephrons, revealed activation of terminal stage of cell death. This phenomenon demonstrates a direct dependence on the dose of electron irradiation - ROD 8 Gy. On the contrary, pre-radiation administration of ascorbic acid statistically significantly reduces the intensity of apoptosis.

DISCUSSION
This study is devoted to immunohistochemical investigation of proliferation and apoptosis of vascular tubules, epitheliocytes of proximal and distal tubules of nephrons against the background of ascorbic acid administration in the model of radiation nephropathy induced by exposure to electrons at 2 Gy ROD and 8 Gy ROD.
It is known that radiotherapy is one of the effective methods of treatment of TNF [15, 16]. However, ionizing radiation can cause damage to healthy tissues falling into the irradiation zone [17]. In modern radiobiology, the following types of radiation therapy of the kidney are most often used: X-rays, alpha-rays, photons, electrons, etc.  The main objective is to increase its safety and reduce the associated side effects on the surrounding tissues. 
Exposure to electrons induces the release of reactive oxygen species (ROS), excessive accumulation of which leads to inhibition of oxidative stress affecting the cell membrane, cell organelles, etc. [18]. [18]. Such damage can alter intracellular signaling cascades by activating genes associated with apoptosis signaling. Also, RFKs can affect DNA, causing mutations of genetic material, reducing cell proliferation and increasing apoptosis [19].

Thanks to recent studies, it is known that radiation-induced cellular aging plays a significant role in the progression of diseases of various organs [20]. In particular, radiation effects on cerebral microvascular endothelial cells demonstrate a link between a single exposure to radiation and the development of neurodegenerative changes in neural tissue [21].
The pathogenetic mechanisms of radiation-induced nephritis are due to the involvement of all components of the kidney, including glomerular, tubular and stromal-vascular components [22].
Ki-67 protein is a marker of cell proliferation and serves as the most important prognostic factor [23].

It should be noted that Ki-67 protein is not expressed in the G0 phase, which is characteristic of most atypical cells under hypoxic conditions. Interestingly, it is this phase of the cell cycle that is associated with increased resistance to radiation exposure. Consequently, low expression of Ki-67 in neoplastic cells may indicate not only their hypoxic state but also potential radioresistance, which is important in assessing the efficacy of radiation therapy [24, 25]. In our study, exposure to electrons at 2 Gy and 8 Gy ROD caused a slight decrease in Ki-67 protein level (in percentage) compared to the control group, which may be due to the time factor. However, this hypothesis is the subject of further studies.

Apoptosis is one of the responses to cytotoxic stress and plays a key role in the pathogenesis of renal dysfunction [26]. Apoptosis is regulated by both external (via "death receptors") and internal (mitochondrial) mechanisms. The extrinsic pathway is triggered by specific ligands (Fas ligand and tumor necrosis factor α) [22]. The intrinsic pathway is activated in response to various forms of cellular stress: hypoxia, ischemia, oxidative stress, etc. [27]. [27]. Thus, under the influence of stress, a biochemical cascade leading to apoptosis is triggered. This process is characterized by chromatin condensation and DNA fragmentation. Apoptosis is confirmed by an increase in the number of cells positive for caspase-3, a marker of the terminal stage of apoptosis. The increase in the number of caspase-3-positive cells in kidney structures detected in the present study against the background of a decrease in Ki-67 protein after a single electron irradiation indicates a shift in the balance between cell proliferation and apoptosis towards the latter. The obtained results partially coincide with the data of other authors who used other types of radiation. Cell pool reduction occurs due to modulation of GSK3-, ERK-, and Ras/Raf/MEK-1 signaling pathways and deactivation of Bcl-2 and induction of p53 protein [28, 29].

In a number of studies, it has been demonstrated that ascorbic acid has protective properties, which contributes to the repair of damaged DNA, as well as to the reduction of radiation-induced injury [30-32]. Pre-radiation administration of ascorbic acid resulted in statistically significant improvement in pathomorphologic changes of renal structures compared to mono-irradiated groups (ROD 2 Gy and ROD 8 Gy). Similar results were obtained by other authors when studying the protective properties of natural antioxidants, in particular, Amphora algae extract, which led to a decrease in inflammatory reactions and improved the functional state of the kidneys in rats [33]. However, it should be noted that the researchers used gamma rather than β-particles; also doses different from ours.
Thus, the obtained results reveal the molecular mechanisms of regulation of proliferation and apoptosis of glomerular, tubular and stromal-vascular component cells of kidneys in the model of radiation nephropathy caused by electron irradiation at 2 Gy and 8 Gy ROD. Pre-radiation administration of ascorbic acid, according to morphological and immunohistochemical data, confirms its protective properties.

CONCLUSION
Local irradiation with electrons at ROD 2 Gy and ROD 8 Gy leads to a shift of the proliferative-apoptotic balance of renal epithelium toward apoptosis. At the same time, ascorbic acid administration reduces the intensity of radiation-induced renal damage and also enhances the efficiency of antioxidant defense.
 
TABLES
Table 1: Evaluation of pathomorphologic changes in control and experimental groups (in points)
Data are presented as mean ± standard deviation (M±SD). *Median [minimum-maximum]: 0 (none), 1 (mild), 2 (moderate), 3 (severe). Statistically significant differences compared to the control group are labeled in the table as Irradiation (a) and Irradiation + AA (b); p < 0.05

FIGURES

 
Figure 1: Kidneys of control and experimental groups. Hematoxylin and eosin staining, magnification. × 200.

 

Figure 2. Kidneys of control and experimental groups. A - immunohistochemical study with antibodies to Ki-67, mag.× 400. B - histogram. Experimental groups (Figure 2B) are numbered according to the study design. Statistically significant differences are indicated by symbols: * - comparison with control group (p<0.05), ** - comparison of group IV with group II (Single Local Dose 2 Gy + AA and  Single Local Dose 2 Gy ) (p<0.01), *** - comparison of group V with group III (Single Local Dose 8 Gy + AA and Single Local Dose 8 Gy) (p<0.001).
Figure 3. Kidneys of control and experimental groups. A - immunohistochemical study with antibodies to caspase-3, mag.× 400. B - histogram. Experimental groups (Figure 3B) are numbered according to the study design. Statistically significant differences are indicated by symbols: * - comparison with control group (p<0.05), ** - comparison of group IV with group II (Single Local Dose 2 Gy + AA and  Single Local Dose 2 Gy ) (p<0.01), *** - comparison of group V with group III (Single Local Dose 8 Gy + AA and Single Local Dose 8 Gy) (p<0.001).
 
 
 
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作者简介

Grigory Demyashkin

I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;

National Medical Research Center of Radiology, Moscow, Russia.

编辑信件的主要联系方式.
Email: dr.dga@mail.ru
ORCID iD: 0000-0001-8447-2600
SPIN 代码: 5157-0177

Doc. Med. Sci., Head of the Department of Pathomorphology, National Medical Research Center of Radiology, Moscow, Russia; Leading Researcher, Scientific and Educational Resource Center "Innovative Technologies of Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis" RUDN University named after Patrice Lumumba; Head of the Laboratory of Histology and Immunohistochemistry, ITMB Sechenov University
俄罗斯联邦, Bolshaya Pirogovskaya str., 2, p.4, Moscow, 119435; 2nd Botkinskiy pr-d, 3, Moscow, 125284.

Zhanna Uruskhanova

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

Email: jey.149@yandex.ru
ORCID iD: 0009-0009-2291-3680

Сo-researcher of First Moscow State University named after I. M. Sechenov. I.M. Sechenov First Moscow State University of the Ministry of Health of Russia (Sechenov University), Moscow, Russia

俄罗斯联邦, Bolshaya Pirogovskaya str., 2, p.4, Moscow, 119435

Sergey Koryakin

National Medical Research Center of Radiology, Moscow, Russia

Email: korsernic@mail.ru
ORCID iD: 0000-0003-0128-4538

PhD, Head of the Department of Radiation Biophysics «NMRC of Radiology»;

 
俄罗斯联邦, 2nd Botkinskiy pr-d, 3, Moscow, 125284

Mikhail Parshenkov

The Institute of Pharmacy of the Sechenov University

Email: misjakj@gmail.com
ORCID iD: 0009-0004-7170-8783

student

俄罗斯联邦, Bolshaya Pirogovskaya str., 2, p.4, Moscow, 119435

Tatyana Dubovaya

N.I. Pirogov Russian National Research Medical University, Moscow, Russia

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

Dr. Sci. (Medicine), Professor
俄罗斯联邦, ul. Ostrovityanova, 1, Moscow, 117997

Galina Rodionova

The Institute of Pharmacy of the Sechenov University

Email: rodionovagalinam@mail.ru
ORCID iD: 0000-0002-0536-9590

Candidate of Pharmaceutical Sciences, Associate Professor of the Department of Pharmaceutical and Toxicological Chemistry. A.P. Arzamastsev Sechenov University
俄罗斯联邦, Bolshaya Pirogovskaya str., 2, p.4, Moscow, 119435

Vladimir Shchekin

The Institute of Clinical Medicine of Sechenov University

Email: dr.shchekin@mail.ru
ORCID iD: 0000-0003-3763-7454

student

俄罗斯联邦, Bolshaya Pirogovskaya str., 2, p.4, Moscow, 119435

Yuliya Ivchenko

The Institute of Clinical Medicine of Sechenov University

Email: ivchenko_yu_v@student.sechenov.ru
ORCID iD: 0000-0003-1336-7277

student

俄罗斯联邦, Bolshaya Pirogovskaya str., 2, p.4, Moscow, 119435

Olga Ionova

The Institute of Clinical Medicine of Sechenov University

Email: olgaionova99@mail.ru
ORCID iD: 0009-0007-9137-6597

student

俄罗斯联邦, Bolshaya Pirogovskaya str., 2, p.4, Moscow, 119435

参考

  1. R. Pinto et al. In Vivo Studies on Radiofrequency (100 kHz–300 GHz) Electromagnetic Field Exposure and Cancer: A Systematic Review. International Journal of Environmental Research and Public Health. 2023. https://doi.org/10.3390/ijerph20032071
  2. Wild CP, Espina C, Bauld L, Bonanni B, Brenner H, Brown K, Dillner J, Forman D, Kampman E, Nilbert M, Steindorf K, Storm H, Vineis P, Baumann M, Schüz J. Cancer Prevention Europe. Molecular Oncology. 2019;13(3):528-534. doi: 10.1002/1878-0261.12455
  3. Wei J, Wang B, Wang H, Meng L, Zhao Q, Li X, et al. Radiation-induced normal tissue damage: oxidative stress and epigenetic mechanisms. Oxidative Medicine and Cellular Longevity. 2019;2019:3010342. doi: 10.1155/2019/3010342
  4. O'Donoghue J. Relevance of external beam dose-response relationships to kidney toxicity associated with radionuclide therapy. Cancer Biotherapy and Radiopharmaceuticals. 2004;19(3):378-87. doi: 10.1089/1084978041425025
  5. Dawson, L., Kavanagh, B., Paulino, A., Das, S., Miften, M., Li, X., Pan, C., Haken, R., & Schultheiss, T. Radiation-associated kidney injury. International journal of radiation oncology, biology, physics. 2010;76(3);108-15. https://doi.org/10.1016/j.ijrobp.2009.02.089
  6. Aratani S, Tagawa M, Nagasaka S, Sakai Y, Shimizu A, Tsuruoka S. Radiation-induced premature cellular senescence involved in glomerular diseases in rats. Scientific Reports. 2018;14;8(1):16812. doi: 10.1038/s41598-018-34893-8
  7. Scholz M, Kraft-Weyrather W, Ritter S, Kraft G. Cell cycle delays induced by heavy ion irradiation of synchronous mammalian cells. International Journal of Radiation Biology. 1994;66(1):59-75. doi: 10.1080/09553009414550951
  8. Mavragani IV, Nikitaki Z, Kalospyros SA, Georgakilas AG. Ionizing Radiation and Complex DNA Damage: From Prediction to Detection Challenges and Biological Significance. Cancers (Basel). 2019;11(11):1789. doi: 10.3390/cancers11111789
  9. Carante MP, Ballarini F. Radiation Damage in Biomolecules and Cells. International Journal of Molecular Sciences. 2020;21(21):8188. doi: 10.3390/ijms21218188
  10. Sia J, Szmyd R, Hau E, Gee HE. Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer. Frontiers in Cell and Developmental Biology. 2020;8:41. doi: 10.3389/fcell.2020.00041
  11. Ashrafizadeh M, Farhood B, Eleojo Musa A, Taeb S, Najafi M. Damage-associated molecular patterns in tumor radiotherapy. International Immunopharmacology. 2020;86:106761. doi: 10.1016/j.intimp.2020.10676
  12. Chen J. The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression. Cold Spring Harbor Perspectives in Medicine. 2016;6(3):a026104. doi: 10.1101/cshperspect.a026104
  13. Demyashkin G.A., Koryakin S.N., Stepanova Y.Y., Shchekin V.I., Shegai P.V. Morphological characterization of kidneys in rats after targeted irradiation with electrons at doses of 2, 4 and 6 G. Veterinary Physician. 2021;9-16. doi: 10.33632/1998-698Х.2021-5-9-16
  14. Demyashkin G.A., Koryakin S.N., Stepanova Y.Y., Shchekin V.I., Shegai P.V. Implication of priceless electronic exposure on historarchitectonics of the robbins of Wistar Rats at Dose of 8 Gr. Veterinary Doctor. 2021;20-26. doi: 10.33632/1998-698Х.2021-4-20-26
  15. Buglione M, Spiazzi L, Urpis M, Baushi L, Avitabile R, Pasinetti N, Borghetti P, Triggiani L, Pedretti S, Saiani F, Fiume A, Greco D, Ciccarelli S, Polonini A, Moretti R, Magrini SM. Light and shadows of a new technique: is photon total-skin irradiation using helical IMRT feasible, less complex and as toxic as the electrons one? Radiation Oncology. 2018; 29;13(1):158. doi: 10.1186/s13014-018-1100-4
  16. Lee MJ, Son HJ. Electron beam radiotherapy for Kaposi's sarcoma of the toe and web. Journal of Cancer Research & Therapy. 2020;16(1):161-163. doi: 10.4103/jcrt.JCRT_115_18
  17. Zanoni M, Cortesi M, Zamagni A, Tesei A. The Role of Mesenchymal Stem Cells in Radiation-Induced Lung Fibrosis. International Journal of Molecular Sciences. 2019;20(16):3876. doi: 10.3390/ijms20163876
  18. Yumusak N, Sadic M, Yucel G, Atilgan HI, Koca G, Korkmaz M. Apoptosis, and cell proliferation in short-term and long-term effects of radioiodine-131-induced kidney damage: an experimental and immunohistochemical study. Nuclear Medicine Communications 2018;39(2):131-139. doi: 10.1097/MNM.0000000000000788
  19. Sheikh BY, Sarker MMR, Kamarudin MNA, Mohan G. Antiproliferative and apoptosis inducing effects of citral via p53 and ROS-induced mitochondrial-mediated apoptosis in human colorectal HCT116 and HT29 cell lines. Biomed Pharmacother. 2017;96:834-846. doi: 10.1016/j.biopha.2017.10.038
  20. Aratani S, Tagawa M, Nagasaka S, Sakai Y, Shimizu A, Tsuruoka S. Radiation-induced premature cellular senescence involved in glomerular diseases in rats. Scientific Reports. 2018;8(1):16812. doi: 10.1038/s41598-018-34893-8
  21. McRobb LS, McKay MJ, Gamble JR, Grace M, Moutrie V, Santos ED, Lee VS, Zhao Z, Molloy MP, Stoodley MA. Ionizing radiation reduces ADAM10 expression in brain microvascular endothelial cells undergoing stress-induced senescence. Aging (Albany NY). 2017;9(4):1248-1268. doi: 10.18632/aging.101225
  22. Ahmad A, Mitrofanova A, Bielawski J, et al. Sphingomyelinase-like phosphodiesterase 3b mediates radiation-induced damage of renal podocytes. FASEB J. 2017;31(2):771-780. doi: 10.1096/fj.201600618R
  23. Freudlsperger C, Freier K, Hoffmann J, Engel M. Ki-67 expression predicts radiosensitivity in oral squamous cell carcinoma. International Journal of Oral & Maxillofacial Surgery. 2012;41(8):965-9. doi: 10.1016/j.ijom.2012.04.014
  24. Fu DR, Kato D, Endo Y, Kadosawa T. Apoptosis and Ki-67 as predictive factors for response to radiation therapy in feline nasal lymphomas. Journal of Veterinary Medical Science. 2016;78(7):1161-6. doi: 10.1292/jvms.15-0693
  25. Couture C, Raybaud-Diogène H, Têtu B, Bairati I, Murry D, Allard J, Fortin A. p53 and Ki-67 as markers of radioresistance in head and neck carcinoma. Cancer. 2002;94(3):713-22. doi: 10.1002/cncr.10232
  26. Kim DH, Park JS, Choi HI, Kim CS, Bae EH, Ma SK, Kim SW. The critical role of FXR is associated with the regulation of autophagy and apoptosis in the progression of AKI to CKD. Cell Death and Disease. 2021;12(4):320. doi: 10.1038/s41419-021-03620-z
  27. Li G, Wang S, Fan Z. Oxidative Stress in Intestinal Ischemia-Reperfusion. Front Med (Lausanne). 2022 Jan 14;8:750731. doi: 10.3389/fmed.2021.750731
  28. Wang Q, Zhou Y, Wang X, Evers BM. Glycogen synthase kinase-3 is a negative regulator of extracellular signal-regulated kinase. Oncogene. 2006;25(1):43-50. doi: 10.1038/sj.onc.1209004
  29. Morel C, Carlson SM, White FM, Davis RJ. Mcl-1 integrates the opposing actions of signaling pathways that mediate survival and apoptosis. Molecular and Cellular Biology. 2009;29(14):3845-3852. doi: 10.1128/MCB.00279-09
  30. J., Allum AJ, Mussallem JT, Froning CE, Haskins AH, Buckner MA, Miller CD, Kato TA. Ascorbic Acid 2-Glucoside Pretreatment Protects Cells from Ionizing Radiation, UVC, and Short Wavelength of UVB. Genes (Basel). 2020;11(3):238. doi: 10.3390/genes11030238
  31. Petruk G, Del Giudice R, Rigano MM, Monti DM. Antioxidants from Plants Protect against Skin Photoaging. Oxidative Medicine and Cellular Longevity. 2018;2018:1454936. doi: 10.1155/2018/1454936
  32. El-Sonbaty SM, Moawed FSM, Elbakry MMM. Amphora algae with low-level ionizing radiation exposure ameliorate D-galactosamine-induced inflammatory impairment in rat kidney. Environmental Toxicology. 2021;36(4):451-459. doi: 10.1002/tox.23050

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