Radiation Nephropathy Research Articles

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

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.

A Case of Radiation Nephropathy Complicated by Tubulointerstitial Nephritis with Predominantly Lymphocyte and Plasma Cell Infiltration.

A 64-year-old Japanese woman presented with gross hematuria and was diagnosed with stage IVB cervical cancer. Renal dysfunction was observed following chemoradiation therapy, and a renal biopsy revealed renal thrombotic microangiopathy (TMA) and tubulointerstitial nephritis (TIN), which are atypical features of radiation nephropathy. Contrast-enhanced computed tomography revealed wedge-shaped areas of high contrast, consistent with areas of high radiation dose in the kidneys, thus leading to the diagnosis of radiation nephropathy. This case underscores the importance of integrating clinical, pathological, and radiological findings for the diagnosis of radiation nephropathy, atypical renal biopsy findings, and a combination of TIN and renal TMA.

Radiation nephropathy: Mechanisms of injury and recovery in a murine model

BackgroundRadiation nephropathy (RN) can be a severe late complication for patients treated with radiotherapy (RT) targeting abdominal and paraspinal tumors. Recent studies investigating the mechanisms of RT-mediated injury in the kidney have demonstrated that RT disrupts the cellular integrity of renal podocytes leading to cell death and loss of renal function. AimTo determine if RT-induced renal dysfunction is associated with alterations in podocyte and glomerular function, and whether RT-induced podocyte alterations were associated with changes in the glomerular basement membrane (GBM). MethodsC57BL/6 mice were treated with focal bilateral X-irradiation using a single dose (SD) of 4 Gy, 10 Gy, or 14 Gy or fractionated dosing (FD) of 5x6Gy or 24x2Gy. Then, 10–40 weeks after RT parameters of renal function were measured, along with glomerular filtration rate (GFR) and glomerular histology, as well as ultrastructural changes in GBM by transmission electron microscopy. ResultsRT treatment resulted in persistent changes in renal function beginning at 10 weeks with little recovery up to 40 weeks post RT. Dose dependent changes were seen with increasing SD but no functional sparing was evident after FD. RT-induced loss of renal function was associated with expansion of the GBM and significant increases in foot process width, and associated with significant reduction in GFR, podocyte loss, and renal fibrosis. ConclusionFor the first time, these data show that expansion of the GBM is one consequence of radiation injury, and disarrangement of the GBM might be associated with the death of podocytes. These data shed new light on the role podocyte injury and GBM in RT-induced renal dysfunction.

Combining network pharmacology and in vitro and in vivo experiments to study the mechanism of Keluoxin in the treatment of radiation nephropathy†.

Radiation nephropathy refers to kidney damage caused by radiation therapy for malignant tumours. Currently, the pathogenesis is unclear and there is a lack of effective treatment methods. With the development of traditional Chinese medicine, the role of traditional Chinese medicine in the protection of radiation nephropathy is receiving increasing attention. Therefore, in this study, we used X-ray intraperitoneal irradiation to construct a mouse model of radiation nephropathy and studied the protective effect of traditional Chinese medicine Keluoxin on radiation nephropathy. We first analysed the potential targets and pathways of Keluoxin in the treatment of radiation nephropathy using network pharmacology methods, combined with in vitro and in vivo experimental verification, to study its potential mechanism. By searching the database, 136 components of Keluoxin were identified. A total of 333 intersectional targets related to radiation nephropathy were obtained. Among them, key targets include IL-6, TNF-α, HIF-1α, STAT1, STAT3, JAK1, JAK2, etc. In in vivo and in vitro experiments, we found that as the irradiation dose increased and time prolonged, kidney damage in mice gradually worsened in a time-dependent and dose-dependent manner. As the irradiation dose increases, the expression of pro-inflammatory factors Il-6, TNF-α, TGF-β increased. Compared with the irradiation group, the intervention of Keluoxin can reduce kidney damage caused by X-ray irradiation and reduce the expression of IL-6, TNF-α, TGF-β, STAT1, STAT3, JAK1, JAK2, etc. These results indicated that Keluoxin can alleviate kidney damage caused by X-ray irradiation, possibly by regulating the JAK/STAT signalling pathway, reducing inflammation levels and oxidative stress damage.

Diagnostic Yield of CT Pulmonary Angiogram in the Diagnosis of Pulmonary Embolism and Its Predictive Factors.

Introduction Computed tomography pulmonary angiography (CTPA) is the reference investigation of choice to diagnose pulmonary embolism (PE). Nevertheless, the use of CTPA should be weighed against its risks, such as radiation and contrast-induced nephropathy. We aim to assess the yield of CTPA in diagnosing PE at a tertiary centre in Malaysia. We also identify predictive factors associated with the yield of CTPA in this cohort. Methods This was a cross-sectional study involving all patients who had had CTPA done at Hospital Tengku Ampuan Afzan, Kuantan, Malaysia, from January 1, 2021, to November 30, 2021. All patients' records were retrieved and reviewed. CTPA images were retrieved from the Radiology Information System (RIS) and Picture Archiving and Communication System (PACS). They were double-reviewed by the authors, with the initial reports redacted from reporting radiologists to prevent reporting bias. The predictive factors were determined using simple logistic regression and multiple logistic regression. Results A total of 351 CTPAs were reviewed, of which 93 were found to be positive for PE, giving rise to an overall CTPA yield of 26.5%. Upon simple logistic regression, factors such as gender, discipline, history of trauma, presence of COVID-19 infection, and pneumonia were found to be associated with positive CTPA. Upon multiple logistic regression, male patients were found to have a higher chance of positive CTPA results. On the other hand, patients with COVID-19 infection and pneumonia have a lower chance of positive results in CTPA. Conclusion The yield of CTPA in diagnosing PE at our institution was acceptable at 26.5%. Upon multiple logistic regression, patients with COVID-19 infection and pneumonia were more likely to have a negative CTPA result, highlighting the need for clinicians to be more prudent in requesting CTPAs in these patients.

Measurement of renal cortical fibrosis by CT scan.

The accurate, non-invasive, and rapid measurement of renal cortical fibrosis is needed for well-defined benchmarks of permanent injury and for use of anti-fibrotic agents. It is also needed for non-invasive and rapid assessment of the chronicity of human renal diseases. We have used a non-human primate model of radiation nephropathy to develop a novel method of size-corrected CT imaging to quantify renal cortical fibrosis. Our method has an area under the receiver operating curve of 0.96, which is superior to any other non-invasive method of measuring renal fibrosis. Our method is suitable for immediate translation to human clinical renal diseases.

Radiation-Induced Nephropathy in the Murine Model Is Ameliorated by Targeting Heparanase.

Agents used to reduce adverse effects common in cancer treatment modalities do not typically possess tumor-suppressing properties. We report that heparanase, an extracellular matrix-degrading enzyme, is a promising candidate for preventing radiation nephropathy. Heparanase promotes tumor development and progression and is upregulated in tumors found in the abdominal/pelvic cavity, whose radiation treatment may result in radiation nephropathy. Additionally, heparan sulfate degradation by heparanase has been linked to glomerular and tubular/interstitial injury in several kidney disorders. In this study, heparanase mRNA levels were measured in HK-2- and HEK-293-irradiated kidney cells and in a murine radiation nephropathy model by qRT-PCR. Roneparstat (specific heparanase inhibitor) was administered to irradiated mice, and 24 h urinary albumin was measured. Kidneys were harvested and weighed 30 weeks post-irradiation. Clinically relevant doses of ionizing radiation upregulated heparanase expression in both renal cells and mice kidneys. A murine model of abdominal radiation therapy revealed that Roneparstat abolished radiation-induced albuminuria-the hallmark of radiation nephropathy. Given the well-documented anti-cancer effects of heparanase inhibition, our findings attest this enzyme to be a unique target in cancer therapy due to its dual action. Targeting heparanase exerts not only direct anti-tumor effects but protects against radiation-induced kidney damage-the backbone of cancer therapy across a range of malignancies.

T Cells Contribute to Pathological Responses in the Non-Targeted Rat Heart following Irradiation of the Kidneys

Heart disease is a significant adverse event caused by radiotherapy for some cancers. Identifying the origins of radiogenic heart disease will allow therapies to be developed. Previous studies showed non-targeted effects manifest as fibrosis in the non-irradiated heart after 120 days following targeted X-irradiation of the kidneys with 10 Gy in WAG/RijCmcr rats. To demonstrate the involvement of T cells in driving pathophysiological responses in the out-of-field heart, and to characterize the timing of immune cell engagement, we created and validated a T cell knock downrat on the WAG genetic backgrou nd. Irradiation of the kidneys with 10 Gy of X-rays in wild-type rats resulted in infiltration of T cells, natural killer cells, and macrophages after 120 days, and none of these after 40 days, suggesting immune cell engagement is a late response. The radiation nephropathy and cardiac fibrosis that resulted in these animals after 120 days was significantly decreased in irradiated T cell depleted rats. We conclude that T cells function as an effector cell in communicating signals from the irradiated kidneys which cause pathologic remodeling of non-targeted heart.

Targeting of Heparanase in the Murine Model Protects against Radiation-Induced Nephropathy

<h3>Purpose/Objective(s)</h3> Adverse effects are common in virtually all types of treatment modalities in cancer including that of radiation therapy. Several agents are clinically used to aid in the reduction of side effects of anti-cancer therapy, however these agents <i>per se</i> are typically not endowed with tumor-suppressing properties. Herein we report that the extracellular matrix (ECM)-degrading enzyme heparanase (a valid target for anti-cancer drug development) is also a promising candidate for interventions aimed at preventing development of radiation nephropathy - a significant side effect of radiation therapy in the treatment of abdominal/pelvic malignancies. Heparanase is the sole mammalian endoglucuronidase that cleaves heparan sulfate in the ECM. The enzymatic action of heparanase has not only been found to promote tumor development and progression at various anatomic sites but is upregulated in essentially all tumor types found in the abdominal/pelvic cavity, whose radiation treatment may result in the development of radiation nephropathy. <h3>Materials/Methods</h3> Eleven-week-old female C3H/HeNHsd mice were administered 10 Gy of radiation using brachytherapy to induce radiation nephropathy. Subcutaneous injections of Roneparstat, a specific heparanase inhibitor, were administered to the mice and urine samples were collected over 24h. Urinary albumin was measured using an ELISA kit. Prior to and following irradiation, heparanase and early growth response (Egr1) transcription factor mRNA levels were determined by qRT-PCR in both HK-2 human proximal tubule epithelial cells and HEK-293 human embryonic kidney cells. <h3>Results</h3> In this study, we evaluated the potential of targeting heparanase to diminish radiation therapy-induced kidney damage. We demonstrated that clinically relevant doses of ionizing radiation upregulate heparanase expression in renal cells (most likely through a transcription factor Egr 1 –dependent mechanism). Moreover, utilizing a murine model of abdominal radiation therapy, we found that the specific heparanase inhibitor, Roneparstat, abolished radiation-induced albuminurea –the hallmark of radiation nephropathy. <h3>Conclusion</h3> Given the well-documented anti-cancer effects of heparanase inhibition, our present findings attest this enzyme as a unique target in the landscape of cancer therapy due to its dual action. Indeed, targeting of heparanase exerts not only direct anti-tumor effects but also protects from kidney damage induced by radiation - the backbone of cancer therapy across a broad range of abdominal/pelvic malignancies.

SMPDL3b modulates radiation-induced DNA damage response in renal podocytes.

The kidneys are radiosensitive and dose-limiting organs for radiotherapy (RT) targeting abdominal and paraspinal tumors. Excessive radiation doses to the kidneys ultimately lead to radiation nephropathy. Our prior work unmasked a novel role for the lipid-modifying enzyme, sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b), in regulating the response of renal podocytes to radiation injury. In this study, we investigated the role of SMPDL3b in DNA double-strand breaks (DSBs) repair in vitro and in vivo. We assessed the kinetics of DSBs recognition and repair along with the ATM pathway and nuclear sphingolipid metabolism in wild-type (WT) and SMPDL3b overexpressing (OE) human podocytes. We also assessed the extent of DNA damage repair in SMPDL3b knock-down (KD) human podocytes, and C57BL6 WT and podocyte-specific SMPDL3b-knock out (KO) mice after radiation injury. We found that SMPDL3b overexpression enhanced DSBs recognition and repair through modulating ATM nuclear shuttling. OE podocytes were protected against radiation-induced apoptosis by increasing the phosphorylation of p53 at serine 15 and attenuating subsequent caspase-3 cleavage. SMPDL3b overexpression prevented radiation-induced alterations in nuclear ceramide-1-phosphate (C1P) and ceramide levels. Interestingly, exogenous C1P pretreatment radiosensitized OE podocytes by delaying ATM nuclear foci formation and DSBs repair. On the other hand, SMPDL3b knock-down, in vitro and in vivo, induced a significant delay in DSBs repair. Additionally, increased activation of apoptosis was induced in podocytes of SMPDL3b-KO mice compared to WT mice at 24 h post-irradiation. Together, our results unravel a novel role for SMPDL3b in radiation-induced DNA damage response. The current work suggests that SMPDL3b modulates nuclear sphingolipid metabolism, ATM nuclear shuttling, and DSBs repair.

Pharmacological Interventions for the Prevention and Treatment of Kidney Injury Induced by Radiotherapy: Molecular Mechanisms and Clinical Perspectives.

More than half of cancer patients need radiotherapy during the course of their treatment. Despite the beneficial aspects, the destructive effects of radiation beams on normal tissues lead to oxidative stress, inflammation, and cell injury. Kidneys are affected during radiotherapy of abdominal malignancies. Radiation nephropathy eventually leads to the release of factors triggering systemic inflammation. Currently, there is no proven prophylactic or therapeutic intervention for the management of radiation-induced nephropathy. This article reviews the biomarkers involved in the pathophysiology of radiation-induced nephropathy and its underlying molecular mechanisms. The efficacy of compounds with potential radioprotective properties on amelioration of inflammation and oxidative stress is also discussed. By outlining the approaches for preventing and treating this critical side effect, we evaluate the potential treatment of radiation-induced nephropathy. Available preclinical and clinical studies on these compounds are also scrutinized.

Contrast-enhanced ultrasound of the kidneys: principles and potential applications.

Contrast-enhanced ultrasound (CEUS) is an extension and an enhanced form of ultrasound that allows real-time evaluation of the various structures in different vascular phases. The last decade has witnessed a widespread expansion of CEUS applications beyond the liver. It has shown fair potential in kidneys and its diagnostic efficacy is comparable to CT and MRI.Ultrasound is the well-accepted screening modality for renal pathologies, however, it underperforms in the characterization of the renal masses. CEUS can be beneficial in such cases as it can help in the characterization of such incidental masses in the same sitting. It has an excellent safety profile with no risk of radiation or contract-related nephropathy. It can aid in the correct categorization of renal cysts into one of the Bosniak classes and has proven its worth especially in complex cysts or indeterminate renal masses (especially Bosniak Category IIF and III). Few studies also describe its potential role in solid masses and in differentiating benign from malignant masses. Other areas of interest include infections, infarctions, trauma, follow-up of local ablative procedures, and VUR. Through this review, the readers shall get an insight into the various applications of CEUS in kidneys, with imaging examples.

The effect of melatonin and carnitine on radiation nephropathy

The effect of melatonin and carnitine on radiation nephropathy

Radiation exposure to the kidney with interstitial iridium-192 high-dose-rate brachytherapy: Extent and rare morphologic changes of radiation nephropathy.

We sought to investigate functional parameters and morphologic changes of the renal parenchyma after treatment with image-guided brachytherapy using single-fraction irradiation (high-dose-rate brachytherapy - HDR-BT) of primary kidney lesions, and primary and secondary lesions of the liver, lymph node, and adrenal gland close to renal structures. Patients ineligible for surgery were included. We prospectively investigated renal function loss within one year via renal scintigraphy and laboratory parameters (KDOQI stage). Radiation exposure to the kidney was measured by volume receiving 5 Gy (V5). We observed morphologic changes on CT or MRI, with follow-up every three months. In total, 35 patients were included (21 males, 14 females). Eight patients were treated for extra-renal malignancies. The mean V5 of the ipsilateral kidney was 70.0 ±42.4 ml equaling to 44.9% parenchymal volume. After renal treatment, V5 renal volume was 77.8 ±42.2 ml (48.7%) compared with 44.0 ±33.0 ml (32.0%) after extra-renal treatment. No significant reduction in KDOQI stage after 12 months of follow-up were found. Three patients developed morphologic changes in the renal parenchyma, with only one showing a decrease in renal function after 12 months. CT-guided HDR-BT is a viable treatment modality for local ablative treatment of renal and adjacent masses, with no significant reduction of the KDOQI stage as a predictor for complications of chronic kidney disease. However, larger cohorts need to be analyzed to identify vulnerable patients, as in rare cases, plain dosimetry seems insufficient to predict renal function loss after HDR-BT.

Radiation nephropathy: Dose, management, and population risk

Radiation nephropathy is renal injury caused by a sufficient dose of irradiation. It can result from external beam irradiation or internal irradiation as might occur from therapeutic radioisotopes. Its usual clinical presentation is as chronic kidney disease occurring some months after irradiation, and it can evolve to end-stage-renal-disease. While the immediate cellular injury from irradiation depends on radiolysis of water and oxidative DNA damage, there is no conclusive evidence for chronic persistent oxidative stress or inflammation as the cause of the multi-tissue scarring that ensues. Antagonists of the renin-angiotensin system are effective treatments for experimental radiation nephropathy but their preferential value in human clinical medicine is unproven.

Renal protection during 177lutetium DOTATATE molecular radiotherapy in children: a proposal for safe amino acid infusional volume during peptide receptor radionuclide therapy.

Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues such as 177-lutetium DOTATATE is an effective treatment modality for neuroendocrine tumours, paragangliomas, and neuroblastomas. However, renal and haematopoietic toxicities are the major limitations of this therapeutic approach. The renal toxicity of PRRT is mediated by renal proximal tubular reabsorption and interstitial retention of the radiolabelled peptides resulting in excessive renal irradiation that can be dose-limiting. To protect the kidneys from PRRT-induced radiation nephropathy, basic amino acids are infused during PRRT as they competitively bind to the proximal tubular cells and prevent uptake of the radionuclide. In adults, 1 L of a basic amino acid solution consisting of arginine and lysine is infused over 4 h commencing 30 min prior to PRRT. However, this volume of amino acids infused over 4 h is excessive in small children and can result in hemodynamic overload. This is all the more relevant in paediatric oncology, as many of the children may have been heavily pretreated and so may have treatment-related renal and or cardiac impairment. We have therefore developed the following guidelines for safe paediatric dosing of renal protective amino acid infusions during PRRT. Our recommendations have been made taking into consideration the renal physiology in small children and the principles of safe fluid management in children.

Acute Proteomic Changes in Non-human Primate Kidney after Partial-body Radiation with Minimal Bone Marrow Sparing.

Near total body exposure to high-dose ionizing radiation results in organ-specific sequelae, including acute radiation syndromes and delayed effects of acute radiation exposure. Among these sequelae are acute kidney injury and chronic kidney injury. Reports that neither oxidative stress nor inflammation are dominant mechanisms defining radiation nephropathy inspired an unbiased, discovery-based proteomic interrogation in order to identify mechanistic pathways of injury. We quantitatively profiled the proteome of kidney from non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing over a time period of 3 wk. Kidney was analyzed by liquid chromatography-tandem mass spectrometry. Out of the 3,432 unique proteins that were identified, we found that 265 proteins showed significant and consistent responses across at least three time points post-irradiation, of which 230 proteins showed strong upregulation while 35 proteins showed downregulation. Bioinformatics analysis revealed significant pathway and upstream regulator perturbations post-high dose irradiation and shed light on underlying mechanisms of radiation damage. These data will be useful for a greater understanding of the molecular mechanisms of injury in well-characterized animal models of partial body irradiation with minimal bone marrow sparing. These data may be potentially useful in the future development of medical countermeasures.

Noninvasive assessment of radiation-induced renal injury in mice

Purpose The kidney is a radiosensitive late-responding normal tissue. Injury is characterized by radiation nephropathy and decline of glomerular filtration rate (GFR). The current study aimed to compare two rapid and cost-effective methodologies of assessing GFR against more conventional biomarker measurements. Methods C57BL/6 mice were treated with bilateral focal X-irradiation (1x14Gy or 5x6Gy). Functional measurements of kidney injury were assessed 20 weeks post-treatment. GFR was estimated using a transcutaneous measurement of fluorescein-isothiocyanate conjugated (FITC)-sinistrin renal excretion and also dynamic contrast-enhanced CT imaging with a contrast agent (ISOVUE-300 Iopamidol). Results Hematoxylin and eosin (H&E) and Periodic acid-Schiff staining identified comparable radiation-induced glomerular atrophy and mesangial matrix accumulation after both radiation schedules, respectively, although the fractionated regimen resulted in less diffuse tubulointerstitial fibrosis. Albumin-to-creatinine ratios (ACR) increased after irradiation (1x14Gy: 100.4 ± 12.2 µg/mg; 6x5Gy: 80.4 ± 3.02 µg/mg) and were double that of nontreated controls (44.9 ± 3.64 µg/mg). GFR defined by both techniques was negatively correlated with BUN, mesangial expansion score, and serum creatinine. The FITC-sinistrin transcutaneous method was more rapid and can be used to assess GFR in conscious animals, dynamic contrast-enhanced CT imaging technique was equally safe and effective. Conclusion This study demonstrated that GFR measured by dynamic contrast-enhanced CT imaging is safe and effective compared to transcutaneous methodology to estimate kidney function.

Involvement of Klotho, TNF‑&alpha; and ADAMs in radiation‑induced senescence of renal epithelial cells.

While radiation nephropathy is a major problem associated with radiotherapy, the exact mechanisms underlying its pathogenesis and the mediators involved in kidney deterioration remain to be elucidated. In view of the finding that senescence is typically increased post-irradiation, the present study examined whether ionizing radiation may cause kidney injury by enhancing premature senescence. The present study explored the relevance of the aging suppressor, Klotho, which has anti-aging activity and is highly expressed in murine renal cells/kidney tissues, under irradiation conditions. Firstly, the effects of radiation on mouse inner medullary collecting duct-3 (mIMCD-3) cells and kidney tissues of mice were assessed. Subsequently, the mRNA expression levels of Klotho, TNF-α and ADAM metallopeptidase domain (ADAM)9/10/17 were analyzed by reverse transcription-quantitative PCR following exposure to radiation. In addition, the levels of these proteins were measured by western blotting or ELISA. The results revealed that irradiation of mIMCD-3 cells clearly triggered cellular senescence. Notably, Klotho gene expression was considerably decreased in radiation-exposed mIMCD-3 cells and in the kidney tissues of irradiated BALB/c mice, and the corresponding translated protein was consistently expressed following radiation exposure. Moreover, expression of TNF-α, a negative regulator of Klotho, was significantly increased, whereas ADAM9/10/17, an ectodomain shedding enzyme of Klotho, was decreased in irradiated mIMCD-3 cells and in the kidney tissues of BALB/c mice. Collectively, these data suggested that TNF-α-mediated inhibition of Klotho expression and blockage of soluble Klotho formation via decreased ADAM expression following irradiation may contribute to the development of renal dysfunction through acceleration of radiation-induced cellular senescence.

RADIOPROTECTIVE PROPERTIES OF POLYPHENOLIC COMPOUNDS OF EDIBLE AND AROMATIC PLANTS

The proliferation of nuclear technologies threatens by the negative impact of ionizing radiation on the human body and requires the search of new effective means for prevention from radiation damage. Informational search in scientific editions and search databases on radioprotective effects of food and aromatic plants, radiation nephropathy and promising herbal drugs for its prevention has been carried out. Methods of analysis, systematization, comparison, generalization of information data have been applied. An overview of the results of experimental phytochemical and clinical studies of domestic and foreign scientists on radioprotective effects of biologically active substances of food and aromatic herbs has been carried out. It is revealed that plant polyphenolic compounds, due to their antioxidant properties, are able to neutralize free radicals and thus leading to a stop of radio-induced chain oxidation reactions in cells, to scavenge and neutralize of lipoperoxyl radicals, chelate ions of metals, as well as to exhibit antimutagenic activity. Radiotherapy might cause several radiation-induced kidney injuries, including radiation nephropathy. Search of promising herbal substances for prevention and alleviation of radiation nephropathy is under active investigation in recent years. Preventive inclusion of radioprotective agents, containing polyphenolic compounds, before irradiation seems to be an obvious renoprotective strategy. The prospect for further phytochemical, pharmacodynamic and toxicological studies of properties of polyphenolic compounds in food and aromatic plants with an objective to create new effective remedies for the prevention and treatment of radiation damage is shown.