RESUMO
Studies of gene-targeted mice identified the roles of the different pro-survival BCL-2 proteins during embryogenesis. However, little is known about the role(s) of these proteins in adults in response to cytotoxic stresses, such as treatment with anti-cancer agents. We investigated the role of BCL-XL in adult mice using a strategy where prior bone marrow transplantation allowed for loss of BCL-XL exclusively in non-hematopoietic tissues to prevent anemia caused by BCL-XL deficiency in erythroid cells. Unexpectedly, the combination of total body γ-irradiation (TBI) and genetic loss of Bcl-x caused secondary anemia resulting from chronic renal failure due to apoptosis of renal tubular epithelium with secondary obstructive nephropathy. These findings identify a critical protective role of BCL-XL in the adult kidney and inform on the use of BCL-XL inhibitors in combination with DNA damage-inducing drugs for cancer therapy. Encouragingly, the combination of DNA damage-inducing anti-cancer therapy plus a BCL-XL inhibitor could be tolerated in mice, at least when applied sequentially.
Assuntos
Anemia/prevenção & controle , Rim/efeitos da radiação , Proteína bcl-X/metabolismo , Proteína bcl-X/farmacologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteína 11 Semelhante a Bcl-2/genética , Dano ao DNA , Feminino , Raios gama , Neoplasias Hematológicas/patologia , Inflamação , Rim/metabolismo , Rim/patologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transcriptoma , Proteínas Supressoras de Tumor/genética , Proteína bcl-X/deficiência , Proteína bcl-X/genéticaRESUMO
PURPOSE: Enzymolysis clearance strategy, characterized by releasing the non-reabsorbable radioactive fragment under the specific cleavage of enzymes, is confirmed to be a safe and effective way to reduce the renal radioactivity accumulation in mice. However, the effectiveness of this strategy in humans remains unknown. Human epidermal growth factor receptor 2 (HER2) is overexpressed in various types of tumors, and radiolabeled HER2 Affibody is believed to be an attractive tool for HER2-targeted theranostics. However, its wide application is limited by the high and persistent renal uptake. In this study, we intend to validate the effectiveness of enzymolysis clearance strategy in reducing renal accumulation by using a modified HER2 Affibody. MATERIALS AND METHODS: A new HER2 Affibody ligand, NOTA-MVK-ZHER2:2891, containing a cleavable Met-Val-Lys (MVK) linker was synthesized and labeled with 68Ga. The microPET imaging study was performed in SKOV-3 tumor mice to assess the uptakes of the control ligand and the MVK one in tumors and kidneys. Seven healthy volunteers were included for biodistribution and dosimetric studies with both the control and MVK ligands performed 1 week apart. Urine and blood samples from healthy volunteers were collected for in vivo metabolism study of the two ligands. Four HER2-positive and two HER2-negative patients were recruited for [68Ga]Ga-NOTA-MVK-ZHER2:2891 PET/CT imaging at 2 and 4 h post-injection (p.i.). RESULTS: [68Ga]Ga-NOTA-MVK-ZHER2:2891 was stable both in PBS and in mouse serum. MicroPET images showed that the tumor uptake of [68Ga]Ga-NOTA-MVK-ZHER2:2891 was comparable to that of [68Ga]Ga-NOTA-ZHER2:2891 at all the time points, while the kidney uptake was significantly reduced 40 min p.i. (P < 0.05). The biodistribution study in healthy volunteers showed that the kidney uptake of MVK ligand was significantly lower than that of the control ligand at 1 h p.i. (P < 0.05), with the SUVmean of 34.3 and 45.8, respectively, while the uptakes of the two ligands in the other organs showed negligible difference. The effective doses of the MVK ligand and the control one were 26.1 and 28.7 µSv/MBq, respectively. The enzymolysis fragment of [68Ga]Ga-NOTA-Met-OH was observed in the urine samples of healthy volunteers injected with the MVK ligand, indicating that the enzymolysis clearance strategy worked in humans. The PET/CT study of patients showed that the range of SUVmax of HER2-positive lesions was 9.4-21, while that of HER2-negative lesions was 2.7-6.2, which suggested that the MVK modification did not affect the ability of ZHER2:2891 structure to bind with HER2. CONCLUSION: We for the first time demonstrated that enzymolysis clearance strategy can effectively reduce renal radioactivity accumulation in humans. This strategy is expected to decrease renal radiation dose of peptide and small protein-based radiotracers, especially in the field of radionuclide therapy.
Assuntos
Radioisótopos de Gálio , Rim , Neoplasias , Receptor ErbB-2 , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Rim/metabolismo , Rim/efeitos da radiação , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/química , Receptor ErbB-2/metabolismo , Proteínas Recombinantes de Fusão/farmacocinética , Distribuição Tecidual , Neoplasias/diagnóstico por imagem , Neoplasias/genéticaRESUMO
Photosensitivity to ultraviolet (UV) light affects up to â¼80% of lupus patients. Sunlight exposure can exacerbate local as well as systemic manifestations of lupus, including nephritis, by mechanisms that are poorly understood. Here, we report that acute skin exposure to UV light triggers a neutrophil-dependent injury response in the kidney characterized by upregulated expression of endothelial adhesion molecules as well as inflammatory and injury markers associated with transient proteinuria. We showed that UV light stimulates neutrophil migration not only to the skin but also to the kidney in an IL-17A-dependent manner. Using a photoactivatable lineage tracing approach, we observed that a subset of neutrophils found in the kidney had transited through UV light-exposed skin, suggesting reverse transmigration. Besides being required for the renal induction of genes encoding mediators of inflammation (vcam-1, s100A9, and Il-1b) and injury (lipocalin-2 and kim-1), neutrophils significantly contributed to the kidney type I interferon signature triggered by UV light. Together, these findings demonstrate that neutrophils mediate subclinical renal inflammation and injury following skin exposure to UV light. Of interest, patients with lupus have subpopulations of blood neutrophils and low-density granulocytes with similar phenotypes to reverse transmigrating neutrophils observed in the mice post-UV exposure, suggesting that these cells could have transmigrated from inflamed tissue, such as the skin.
Assuntos
Inflamação/sangue , Rim/metabolismo , Neutrófilos/efeitos da radiação , Pele/efeitos da radiação , Animais , Calgranulina B/genética , Movimento Celular/efeitos da radiação , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Inflamação/etiologia , Inflamação/patologia , Interleucina-17/genética , Rim/lesões , Rim/patologia , Rim/efeitos da radiação , Lipocalina-2/genética , Camundongos , Neutrófilos/metabolismo , Neutrófilos/patologia , Pele/lesões , Raios Ultravioleta/efeitos adversos , Molécula 1 de Adesão de Célula Vascular/genéticaRESUMO
Excessive exposure to light is a global issue. Artificial light pollution has been shown to disrupt the body's natural circadian rhythm. To investigate the impacts of light on metabolism, we studied Sprague-Dawley rats chronically exposed to red or blue light during daytime or nighttime. Rats in the experimental group were exposed to extended light for 4â¯hours during daytime or nighttime to simulate the effects of excessive light usage. Strikingly, we found systemic metabolic alterations only induced by blue light during daytime. Furthermore, we conducted metabolomic analyses of the cerebrospinal fluid, serum, heart, liver, spleen, adrenal, cerebellum, pituitary, prostate, spermatophore, hypothalamus and kidney from rats in the control and blue light exposure during daytime. Signiï¬cant changes in metabolites have been observed in cerebrospinal fluid, serum, hypothalamus and kidney of rats exposed to blue light during daytime. Metabolic alterations observed in rats encompassing pyruvate metabolism, glutathione metabolism homocysteine degradation, phosphatidylethanolamine biosynthesis, and phospholipid biosynthesis, exhibit analogous patterns to those inherent in specific physiological processes, notably neurodevelopment, cellular injury, oxidative stress, and autophagic pathways. Our study provides insights into tissue-specific metabolic changes in rats exposed to blue light during the daytime and may help explain potential mechanisms of photopathogenesis.
Assuntos
Ritmo Circadiano , Luz , Ratos Sprague-Dawley , Animais , Masculino , Ratos , Metabolômica , Estresse Oxidativo/efeitos da radiação , Rim/metabolismo , Rim/efeitos da radiação , Luz AzulRESUMO
Through an ex vivo experimental study, we aimed to compare the effects of the Ho: YAG laser Virtual Basket (VB™) modulation and a Thulium fiber laser (TFL) on kidney tissue in different environments and using laser configurations. The 100 W Ho: YAG (Cyber Ho, Quanta System, Italy) and 60 W TFL (Fiber Dust, Quanta System, Italy) laser devices were used. The following laser settings were selected: power in the range of 10-60 W, frequency of 20-40 Hz, and energy of 0.5-1-1.5 J. A medium pulse duration of 600 µsec was used for VB™, while short (spdTFL; 50 µsec) and long (lpdTFL; 15,000 µsec) were used for TFL. The tissue's incision depth (ID), vaporization area (VA), coagulation area (CA), total laser area (TLA = VA + CA), surface section (SS), and lateral effect (LE) were measured. In total, 108 experiments were conducted. No statistically significant difference in mean VA, TLA, ID, LE, or SS was observed between VB™, spdTFL, and lpdTFL in the low-power output group in saline (p > 0.05). However, the mean CA was statistically significantly higher for VB™ (p = 0.005). In saline and high-power output group, the mean VA, CA, TLA, LE, and ID were higher when using lpdTFL than other pulse durations (p = 0.001, p = 0.001, p = 0.001, p = 0.006, and p = 0.001, respectively). Similar to lpdTFL, VB™ may provide controlled dissection and incision as well as haemostasis. At different laser settings, the individual effects of laser properties (such as pulse length, energy and frequency) on tissue may be more significant.
Assuntos
Rim , Lasers de Estado Sólido , Túlio , Lasers de Estado Sólido/uso terapêutico , Rim/cirurgia , Rim/efeitos da radiação , Animais , Suínos , Terapia a Laser/métodos , Terapia a Laser/instrumentaçãoRESUMO
Despite the therapeutic advances in treating malignancies, the efficient radiotherapeutic approaches with deprived adverse reactions still represent a potential clinical inquiry. The current study aims to elucidate the role of gallic acid (GA) in modifying the hazardous renal cytotoxicity induced by acute exposure to radiation. The MTT test was used to evaluate the viability of Vero cells exposed to 2 Gy gamma radiation with or without incubation of GA. In an in vivo model, male Wistar rats were divided into four experimental groups (n = 6): Control, Irradiated (IRR, 5 Gy), GA (100 mg/kg, i.p.) + IRR, and Glycogen synthase kinase inhibitor (GSKI, 3 mg/kg, i.p.) + IRR. Based on the MTT toxicity assay, from 0 and up to 5 µM dosages of GA did not demonstrate any cytotoxicity to Vero cells. The optimal GA dose that could protect the cells from radiation was 5 µM. Furthermore, GA exerted a protective effect from gamma radiation on renal tissue as indicated by corrected renal functions, decreased LDH level in serum, and balanced oxidative status, which is indicated by decreased tissue contents of NOx and TBARS with a significant increase of reduced GSH. These outcomes were inferred by the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) expression. The overall molecular impact of radiation in damaging the renal tissue may be explained by modifying the upstream AKT activity and its downstream targets GSK-3ß/Notch-1. Here, we concluded that the anticipated adverse reaction in the course of radiation exposure could be protected by daily administration of GA.
Assuntos
Ácido Gálico , Raios gama , Glicogênio Sintase Quinase 3 beta , Rim , Ratos Wistar , Receptor Notch1 , Animais , Ácido Gálico/farmacologia , Masculino , Glicogênio Sintase Quinase 3 beta/metabolismo , Rim/efeitos dos fármacos , Rim/efeitos da radiação , Células Vero , Raios gama/efeitos adversos , Receptor Notch1/metabolismo , Chlorocebus aethiops , Ratos , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Protetores contra Radiação/farmacologiaRESUMO
Recombinant α1-microglobulin (A1M) is proposed as a protector during 177Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of 177Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but the radioprotective action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after 177Lu-octreotate and/or A1M administration. Mice were injected with 177Lu-octreotate and/or A1M, while control mice received saline or A1M vehicle solution. Bone marrow, kidney medulla, and kidney cortex were sampled after 24 h or 7 d. The differential protein expression was analyzed with tandem mass spectrometry. The dosimetric estimation was based on 177Lu activity in the kidney. PHLDA3 was the most prominent radiation-responsive protein in kidney tissue. In general, no statistically significant difference in the expression of radiation-related proteins was observed between the irradiated groups. Most canonical pathways were identified in bone marrow from the 177Lu-octreotate+A1M group. Altogether, a tissue-dependent proteomic response followed exposure to 177Lu-octreotate alone or together with A1M. Combining 177Lu-octreotate with A1M did not inhibit the radiation-induced protein expression early after exposure, and late effects should be further studied.
Assuntos
alfa-Globulinas , Octreotida , Proteômica , Animais , alfa-Globulinas/metabolismo , Camundongos , Octreotida/farmacologia , Octreotida/análogos & derivados , Proteômica/métodos , Proteínas Recombinantes/farmacologia , Rim/metabolismo , Rim/efeitos da radiação , Rim/efeitos dos fármacos , Masculino , Medula Óssea/efeitos da radiação , Medula Óssea/metabolismo , Medula Óssea/efeitos dos fármacos , Órgãos em Risco/efeitos da radiação , Proteoma/metabolismo , Protetores contra Radiação/farmacologiaRESUMO
Understanding the hazards of space radiation is imperative as astronauts begin voyaging on missions with increasing distances from Earth's protective shield. Previous studies investigating the acute or long-term effects of specific ions comprising space radiation have revealed threats to organs generally considered radioresistant, like the brain, and have shown males to be more vulnerable than their female counterparts. However, astronauts will be exposed to a combination of ions that may result in additive effects differing from those of any one particle species. To better understand this nuance, we irradiated 4-month-old male and female, wild-type and Alzheimer's-like mice with 0, 0.5, or 0.75 Gy galactic cosmic ray simulation (GCRsim) or 0, 0.75, or 2 Gy gamma radiation (wild-type only). At 11 months, mice underwent brain and heart MRIs or behavioral tests, after which they were euthanized to assess amyloid-beta pathology, heart and kidney gene expression and fibrosis, and plasma cytokines. Although there were no changes in amyloid-beta pathology, we observed many differences in brain MRIs and behavior, including opposite effects of GCRsim on motor coordination in male and female transgenic mice. Additionally, several genes demonstrated persistent changes in the heart and kidney. Overall, we found sex- and genotype-specific, long-term effects of GCRsim and gamma radiation on the brain, heart, and kidney.
Assuntos
Doença de Alzheimer , Encéfalo , Radiação Cósmica , Raios gama , Coração , Rim , Camundongos Transgênicos , Animais , Doença de Alzheimer/genética , Doença de Alzheimer/etiologia , Doença de Alzheimer/patologia , Feminino , Masculino , Raios gama/efeitos adversos , Encéfalo/efeitos da radiação , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , Camundongos , Rim/efeitos da radiação , Rim/metabolismo , Rim/patologia , Coração/efeitos da radiação , Radiação Cósmica/efeitos adversos , Mutação , Caracteres Sexuais , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/genética , Modelos Animais de Doenças , Fatores SexuaisRESUMO
BACKGROUND: Radiotherapy can cause kidney injury in patients with cervical cancer. This study aims to investigate the possible molecular mechanisms by which CpG-ODNs (Cytosine phosphate guanine-oligodeoxynucleotides) regulate the PARP1 (poly (ADP-ribose) polymerase 1)/XRCC1 (X-ray repair cross-complementing 1) signaling axis and its impact on radiation kidney injury (RKI) in cervical cancer radiotherapy. METHODS: The GSE90627 dataset related to cervical cancer RKI was obtained from the Gene Expression Omnibus (GEO) database. Bioinformatics databases and R software packages were used to analyze the target genes regulated by CpG-ODNs. A mouse model of RKI was established by subjecting C57BL/6JNifdc mice to X-ray irradiation. Serum blood urea nitrogen (BUN) and creatinine levels were measured using an automated biochemical analyzer. Renal tissue morphology was observed through HE staining, while TUNEL staining was performed to detect apoptosis in renal tubular cells. ELISA was conducted to measure levels of oxidative stress-related factors in mouse serum and cell supernatant. An in vitro cell model of RKI was established using X-ray irradiation on HK-2 cells for mechanism validation. RT-qPCR was performed to determine the relative expression of PARP1 mRNA. Cell proliferation activity was assessed using the CCK-8 assay, and Caspase 3 activity was measured in HK-2 cells. Immunofluorescence was used to determine γH2AX expression. RESULTS: Bioinformatics analysis revealed that the downstream targets regulated by CpG-ODNs in cervical cancer RKI were primarily PARP1 and XRCC1. CpG-ODNs may alleviate RKI by inhibiting DNA damage and oxidative stress levels. This resulted in significantly decreased levels of BUN and creatinine in RKI mice, as well as reduced renal tubular and glomerular damage, lower apoptosis rate, decreased DNA damage index (8-OHdG), and increased levels of antioxidant factors associated with oxidative stress (SOD, CAT, GSH, GPx). Among the CpG-ODNs, CpG-ODN2006 had a more pronounced effect. CpG-ODNs mediated the inhibition of PARP1, thereby suppressing DNA damage and oxidative stress response in vitro in HK-2 cells. Additionally, PARP1 promoted the formation of the PARP1 and XRCC1 complex by recruiting XRCC1, which in turn facilitated DNA damage and oxidative stress response in renal tubular cells. Overexpression of either PARP1 or XRCC1 reversed the inhibitory effects of CpG-ODN2006 on DNA damage and oxidative stress in the HK-2 cell model and RKI mouse model. CONCLUSION: CpG-ODNs may mitigate cervical cancer RKI by blocking the activation of the PARP1/XRCC1 signaling axis, inhibiting DNA damage and oxidative stress response in renal tubule epithelial cells.
Assuntos
Citosina , Rim , Neoplasias do Colo do Útero , Animais , Feminino , Humanos , Camundongos , Creatinina , Dano ao DNA , Guanina/farmacologia , Rim/lesões , Rim/efeitos da radiação , Camundongos Endogâmicos C57BL , Oligodesoxirribonucleotídeos/farmacologia , Estresse Oxidativo , Fosfatos/farmacologia , Poli(ADP-Ribose) Polimerase-1/farmacologia , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
This work was designed to estimate the protective effect of Saraca indica L. leaves ethanolic exract against γ-irradiation induced renal damage in rats. Phytochemical examinations of S. indica L. leaves extract resulted in the separation of three flavanone glycosides: Astilibin (1), Neoastilbin (2), and Eriodictyol-7-O-α-l-rhamnopyranoside (3); two flavonols: Quercetin (4) and Quercetin-3-O-α-l-arabinopyranosyl-(1'''-6'')-O-ß-D-galactopyranoside (5) in addition of Gallic acid (6) and methyl gallate (7). Their structures elucidated by chemical evidences and spectroscopic analysis (1 and 2D-NMR, -ESI-MS, UV). Female rats were used and classified into: control, Ext (200 mg/kg body wt/day orally for 7 days), IRR (8Gy), Ext + IRR, and Sily+IRR groups (received silymarin 50 mg/kg b.wt orally as reference drug). Results showed that S. indica L. leaves extract ameliorated the kidney function tests, hs-CRP, IL-1ß, ACE, TNF-α, GSH, and MDA as well as, decreased the histopathological changes of kidney. In conclusion, S. indica L. leaves extract had a renoprotective activity against irradiation induced renal injury due to its flavononid contents.
Assuntos
Fabaceae/química , Flavonoides/farmacologia , Raios gama/efeitos adversos , Rim/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Lesões Experimentais por Radiação/prevenção & controle , Animais , Antioxidantes/metabolismo , Feminino , Flavonoides/isolamento & purificação , Rim/metabolismo , Rim/patologia , Rim/efeitos da radiação , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Substâncias Protetoras/isolamento & purificação , Ratos , Irradiação Corporal TotalRESUMO
d-Galactosamine (d-GalN) is a well-known toxin that causes many metabolic and morphological abnormalities resulting in advanced renal failure and liver damage. Occupational exposure to low-level ionizing radiation (<1 Gy) was shown to enhance cell protection via attenuating an established inflammatory process. The present study was therefore aimed to investigate the protective impact of Amphora coffaeiformis extract and low dose gamma radiation against d-GalN induced renal damage in rats. Forty-eight adult male Swiss albino rats were distributed equally into eight groups. The measurements included antioxidants activities (superoxide dismutase, catalase and glutathione peroxidase) as well as lipid peroxidation level in kidney tissue. Also, kidney function tests and inflammatory markers (tumor necrosis factor alpha and nuclear factor kappa-light-chain-enhancer of activated B cells) were measured. Additionally, relative quantification of kidney nuclear factor erythroid 2-related factor 2 (Nrf-2) gene was estimated. Histopathological examination was also performed in kidney tissue. The results revealed decreases in antioxidant activities and downregulation of Nrf-2 expression accompanied by increases in lipid peroxidation level, kidney function tests and inflammatory markers in d-GaIN group. The treatment with Amphora algal extract and low dose gamma radiation ameliorated the previous measurements which were harmony with histopathological findings. In conclusion, A coffaeiformis extract and low dose gamma radiation provided marked functional and histological effects in the treating acute renal damage induced by d-GalN in rats.
Assuntos
Antioxidantes/farmacologia , Diatomáceas/química , Galactosamina/toxicidade , Rim/efeitos dos fármacos , Rim/imunologia , Radiação Ionizante , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/toxicidade , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Inflamação , Rim/patologia , Rim/efeitos da radiação , Testes de Função Renal , Dose Letal Mediana , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Masculino , Fator 2 Relacionado a NF-E2/genética , Doses de Radiação , Ratos , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Irradiação Corporal TotalRESUMO
The development of dosimetry and studies in peptide receptor radionuclide therapy (PRRT) over the past two decades are reviewed. Differences in kidney and bone marrow toxicity reported between 90Y, 177Lu and external beam radiotherapy (EBRT) are discussed with regard to the physical properties of these beta emitter radionuclides. The impact of these properties on the response to small and large tumors is also considered. Capacities of the imaging modalities to assess the dosimetry to target tissues are evaluated. Studies published in the past two years that confirm a red marrow uptake in 177Lu-DOTATATE therapy, as already observed 20 years ago in 86Y-DOTATOC PET studies, are analyzed in light of the recent developments in the transferrin transport mechanism. The review enlightens the importance (i) of using state-of-the-art imaging modalities, (ii) of individualizing the activity to be injected with regard to the huge tissue uptake variability observed between patients, (iii) of challenging the currently used but inappropriate blood-based red marrow dosimetry and (iv) of considering individual tandem therapy. Last, a smart individually optimized tandem therapy taking benefit of the bi-orthogonal toxicity-response pattern of 177Lu-DOTATATE and of 90Y-DOTATOC is proposed.
Assuntos
Medula Óssea/efeitos da radiação , Rim/efeitos da radiação , Neoplasias/radioterapia , Órgãos em Risco/efeitos da radiação , Compostos Radiofarmacêuticos/administração & dosagem , Planejamento da Radioterapia Assistida por Computador/métodos , Receptores de Peptídeos/metabolismo , Animais , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Dosagem RadioterapêuticaRESUMO
The biological effects of extremely low-frequency electromagnetic fields (ELF-EMF) exposure are not fully clarified. We conducted this investigation to explore the effects of ELF-EMF on hematologic and biochemical indexes in adult rats. Thirty adult male Sprague-Dawley rats were exposed to ELF-EMF at 1 mT for 24 weeks, while another 30 SD rats were sham exposed. During the exposure, peripheral blood was collected every 4 weeks to analyze the hematologic parameters and biochemical indexes. The morphology of liver and kidney was detected by hematoxylin-eosin staining at the end of the experiment. Exposed to ELF-EMF at 1 mT did not exert any statistic difference on hematologic parameters including total white blood cell count, neutrophil ratio, lymphocyte ratio, red blood cells, hemoglobin concentration and platelets count, compared to the control group. Similarly, biochemical indexes, such as glucose, lipid profile, liver function and renal function, were not affected by ELF-EMF exposure. In addition, no morphological change was observed in the liver and kidney from the exposure group. The exposure to ELF-EMF at the intensity of 1 mT for 24 weeks did not affect hematologic and biochemical indexes in adult rats.
Assuntos
Análise Química do Sangue , Campos Eletromagnéticos/efeitos adversos , Animais , Rim/metabolismo , Rim/efeitos da radiação , Fígado/metabolismo , Fígado/efeitos da radiação , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
We studied the effect of long-term light deprivation which began at different stages of ontogeny on the content of α-tocopherol in rats during the first 3 months of postnatal development. In the offspring postnatally exposed to constant darkness, the level of α-tocopherol in the liver, kidneys, heart, skeletal muscles, and lungs was significantly decreased at the early stages of postnatal ontogeny (2 weeks and 1 month). In rats kept under constant darkness after birth, the content of α-tocopherol in the lungs was also reduced at the age of 1 month. The modulating effect of light deprivation on the level of α-tocopherol can be associated both with the impact of disturbed circadian rhythms and with increased content of melatonin in the body.
Assuntos
Rim/metabolismo , Luz , Fígado/metabolismo , Pulmão/metabolismo , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , alfa-Tocoferol/metabolismo , Animais , Feminino , Rim/efeitos da radiação , Fígado/efeitos da radiação , Pulmão/efeitos da radiação , Masculino , Músculo Esquelético/efeitos da radiação , Ratos , Ratos Wistar , alfa-Tocoferol/efeitos da radiaçãoRESUMO
Effective therapeutic strategies are needed to preserve renal function in patients with atherosclerotic renal artery stenosis (ARAS). Low-energy shockwave therapy (SW) and adipose tissue-derived mesenchymal stem/stromal cells (MSCs) both stimulate angiogenesis repair of stenotic kidney injury. This study tested the hypothesis that intrarenal delivery of adipose tissue-derived MSCs would enhance the capability of SW to preserve stenotic kidney function and structure. Twenty-two pigs were studied after 16 weeks of ARAS, ARAS treated with a SW regimen (bi-weekly for 3 weeks) with or without subsequent intrarenal delivery of adipose tissue-derived MSCs and controls. Four weeks after treatment, single-kidney renal blood flow (RBF) before and after infusion of acetylcholine, glomerular filtration rate (GFR), and oxygenation were assessed in vivo and the renal microcirculation, fibrosis, and oxidative stress ex vivo. Mean arterial pressure remained higher in ARAS, ARAS + SW, and ARAS + SW + MSC compared with normal. Both SW and SW + MSC similarly elevated the decreased stenotic kidney GFR and RBF observed in ARAS to normal levels. Yet, SW + MSC significantly improved RBF response to acetylcholine in ARAS, and attenuated capillary loss and oxidative stress more than SW alone. Density of larger microvessels was similarly increased by both interventions. Therefore, although significant changes in functional outcomes were not observed in a short period of time, adjunct MSCs enhanced pro-angiogenic effect of SW to improve renal microvascular outcomes, suggesting this as an effective stratege for long-term management of renovascular disease.
Assuntos
Aterosclerose/terapia , Tratamento por Ondas de Choque Extracorpóreas , Rim/efeitos da radiação , Obstrução da Artéria Renal/terapia , Animais , Aterosclerose/etiologia , Aterosclerose/patologia , Fibrose/patologia , Fibrose/terapia , Taxa de Filtração Glomerular/efeitos da radiação , Humanos , Rim/patologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos da radiação , Microcirculação/efeitos da radiação , Microvasos/patologia , Microvasos/efeitos da radiação , Estresse Oxidativo/efeitos da radiação , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/patologia , Circulação Renal/efeitos da radiação , SuínosRESUMO
Previous studies have shown that alterations in the mechanical properties of cells may be associated with the onset and progression of some forms of pathology. In this paper, an experimental study of two types of cells, renal (cancer) and bladder (cancer) cells, is described which used acoustic radiation force (ARF) generated by a high-frequency ultrasound focusing transducer and performed on the operating platform of an inverted light microscope. Comparing images of cancer cells with those of normal cells of the same kind, we find that the cancer cells are more prone to deform than normal cells of the same kind under the same ARF. In addition, cancer cells with higher malignancy are more deformable than those with lower malignancy. This means that the deformability of cells may be used to distinguish diseased cells from normal ones, and more aggressive cells from less aggressive ones, which may provide a more rapid and accurate method for clinical diagnosis of urological disease in the future.
Assuntos
Acústica , Neoplasias Renais/diagnóstico por imagem , Rim/citologia , Ultrassom , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/citologia , Algoritmos , Linhagem Celular Tumoral , Progressão da Doença , Humanos , Rim/efeitos da radiação , Neoplasias Renais/fisiopatologia , Fenômenos Mecânicos , Transdutores , Bexiga Urinária/efeitos da radiação , Neoplasias da Bexiga Urinária/fisiopatologiaRESUMO
BACKGROUND: An elevated thyroid stimulating hormone (TSH) level is essential for the uptake of radioiodine into thyroid remnants and residual thyroid cancer in patients undergoing high-dose radioiodine therapy (HD-RIT). Recently, the use of recombinant human thyroid stimulating hormone (rh-TSH) has increased in preference over the conventional method of thyroid hormone withdrawal (THW). However, the clinical influences of the two methods, aside from the therapeutic effects, have not been widely evaluated. The aim of this work was to investigate the influences of the two methods, particularly on the renal function and external radiation dose rate (EDR) from patients undergoing HD-RIT. METHODS: From February 2012 to November 2016, 667 patients (M:F=138:529, mean age: 47.7±11.8 years), who underwent first HD-RIT (120, 150, or 180 mCi, 1 mCi=37 MBq) for ablation of remnant thyroid tissue or residual thyroid cancer, were enrolled. Patients who were proven to have distant metastasis to lung or bone were excluded. Low- to high-risk patients based on 2015 American thyroid association management guidelines who underwent first HD-RIT in our department were included. The period from total thyroidectomy to HD-RIT was limited within 12 months. The following parameters were collected and evaluated: age, gender, histology type and TNM stage of thyroid cancer, glomerular filtration rate on the admission day for total thyroidectomy (baseline GFR), GFR on the day of HD-RIT (follow-up GFR), thyroglobulin (Tg) and TSH levels on the day of HD-RIT, and EDR on the discharge day after HD-RIT. RESULTS: There were 386 patients using the THW method and 281 patients choosing the rh-TSH method. The baseline GFR of the THW group (106±16 mL/min/1.73 m2) and that of the rh-TSH group (104±17 mL/min/1.73 m2) were within normal limits and there was no significant difference. However, follow-up GFR of the THW group (84±17 mL/min/1.73 m2) was much lower than that of the rh-TSH group (104±16 mL/min/1.73 m2) (P=0.000). In the THW group, the follow-up GFR decreased significantly (P=0.000), yet the follow-up GFR of the rh-TSH group was not statistically different when compared with its baseline GFR (P=0.142). EDRs were lower in all rh-TSH subgroups compared to those of THW subgroups with statistical significance. Tg and TSH levels were not different between the two groups, excluding a few small-sized subgroups analyses. CONCLUSIONS: In this retrospective analysis of renal function and EDR, the use of rh-TSH appears to help maintain renal function and finally decrease EDR in contrast to the THW method when undergoing HD-RIT.
Assuntos
Técnicas de Ablação , Radioisótopos do Iodo/uso terapêutico , Rim/fisiopatologia , Alta do Paciente , Doses de Radiação , Neoplasias da Glândula Tireoide/fisiopatologia , Neoplasias da Glândula Tireoide/radioterapia , Feminino , Humanos , Rim/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estudos RetrospectivosRESUMO
Ultraviolet radiation is an ecological factor that directly affects terrestrial organisms through suppression of immunity or damage to internal organs. The present study assessed the effects of ultraviolet A (UVA) radiation on the kidneys of both wild-type (WT) and p53-deficient medaka (Oryzias latipes) and evaluated which strain was more resistant to the effects of UVA. Fish were divided into four groups: control group 1 (Cwt and Cp53), kept for 3 days without UVA exposure; group 2 (1wt and 1p53), fish exposed daily to UVA for 1 h day-1 for 3 days; group 3 (2wt and 2p53), fish exposed daily to UVA for 2 h day-1 for 3 days; and group 4 (3wt and 3p53), fish exposed daily to UVA for 3 h day-1 for 3 days. Samples of tissues were obtained 24 h after UVA exposure. The most obvious histopathological changes induced by UVA radiation in kidney tissues of both strains of medaka (WT and p53-deficient) were high levels of vacuolation of tubular cells followed by necrosis. The tubular segments lost their normal shape which appeared like a network structure and their cells with clear cytoplasm. Necrosis of lymphoid tissues and spots of brown pigmentation (possibly melanomacrophages) were sporadically seen in interstitial lymphoid tissues, while shrinkage of glomeruli, diminution of periodic acid-Schiff staining, and increased amount of collagenous fibers were observed. Our results confirmed the harmful effects of UVA radiation on kidney tissues of both WT and p53-deficient medaka. However, WT medaka was affected more than p53-deficient medaka.
Assuntos
Rim/efeitos da radiação , Oryzias/metabolismo , Proteína Supressora de Tumor p53/genética , Raios Ultravioleta , Animais , Feminino , Rim/patologia , Necrose , Proteína Supressora de Tumor p53/deficiênciaRESUMO
Power-frequency electromagnetic fields (PF-EMFs) at 50 Hz are potential health risk factors. This study aimed to explore the effects of long-term exposure to 50-Hz PF-EMFs on general physiological conditions in Sprague-Dawley (SD) rats. During a 24-week exposure period, the body mass and water and food intake of the animals were recorded regularly. The hematologic parameters were detected every 12 weeks, and blood chemistry analyses were performed every 4 weeks. After sacrifice, morphology was identified by hematoxylin-eosin, Masson, and immunohistochemical staining. Fibrosis-related gene expression and oxidative stress status were also detected. Compared with the control group, exposure to 30, 100, or 500 µT PF-EMF did not exert any effect on body mass, food intake, or water intake. Similarly, no significant differences were found in hematologic parameters or blood chemistry analyses among these groups. Furthermore, morphological assays showed that exposure to PF-EMFs had no influence on the structure of the liver or kidney. Finally, fibrosis-related gene expression and oxidative stress status were unaltered by PF-EMF exposure. The present study indicates that 24 weeks of exposure to PF-EMFs at intensities of 30, 100, or 500 µT might not affect hemograms, blood chemistry, fibrosis, or oxidative stress in the liver or kidney in SD rats. © 2020 Bioelectromagnetics Society.
Assuntos
Análise Química do Sangue , Campos Eletromagnéticos/efeitos adversos , Rim/patologia , Rim/efeitos da radiação , Cirrose Hepática/etiologia , Estresse Oxidativo/efeitos da radiação , Animais , Regulação da Expressão Gênica/efeitos da radiação , Testes Hematológicos , Rim/metabolismo , Cirrose Hepática/sangue , Cirrose Hepática/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Radon therapy has been traditionally performed globally for oxidative stress-related diseases. Many researchers have studied the beneficial effects of radon exposure in living organisms. However, the effects of thoron, a radioisotope of radon, have not been fully examined. In this study, we aimed to compare the biological effects of radon and thoron inhalation on mouse organs with a focus on oxidative stress. Male BALB/c mice were randomly divided into 15 groups: sham inhalation, radon inhalation at a dose of 500 Bq/m3 or 2000 Bq/m3, and thoron inhalation at a dose of 500 Bq/m3 or 2000 Bq/m3 were carried out. Immediately after inhalation, mouse tissues were excised for biochemical assays. The results showed a significant increase in superoxide dismutase and total glutathione, and a significant decrease in lipid peroxide following thoron inhalation under several conditions. Additionally, similar effects were observed for different doses and inhalation times between radon and thoron. Our results suggest that thoron inhalation also exerts antioxidative effects against oxidative stress in organs. However, the inhalation conditions should be carefully analyzed because of the differences in physical characteristics between radon and thoron.