ABSTRACT
Radiotherapy is one of the three main treatments for tumors. Almost 70% of tumor patients undergo radiotherapy at different periods. Although radiotherapy can enhance the local control rate of tumors and patients' quality of life, normal tissues often show radiation damage following radiotherapy. In recent years, several studies have shown that exosomes could be biomarkers for diseases and be involved in the treatment of radiation damage. Exosomes are nanoscale vesicles containing complex miRNAs and proteins. They can regulate the inflammatory response, enhance the regeneration effect of damaged tissue, and promote the repair of damaged tissues and cells, extending their survival time. In addition, their functions are achieved by paracrine signaling. In this review, we discuss the potential of exosomes as biomarkers and introduce the impact of exosomes on radiation damage in different organs and the hematopoietic system in detail.
Subject(s)
Exosomes/physiology , Exosomes/radiation effects , Radiation Injuries, Experimental/therapy , Radiation Injuries/therapy , Animals , Biomarkers , Humans , Quality of Life , Radiation Injuries/diagnosis , Radiation Injuries, Experimental/diagnosis , Radiotherapy/adverse effectsABSTRACT
Background Medium-dose (25 gray) x-ray radiation therapy has recently been performed on patients with refractory ventricular tachyarrhythmias. Unlike x-ray, carbon ion and proton beam radiation can deliver most of their energy to the target tissues. This study investigated the electrophysiological and pathological changes caused by medium-dose carbon ion and proton beam radiation in the left ventricle (LV). Methods and Results External beam radiation in the whole LV was performed in 32 rabbits. A total of 9 rabbits were not irradiated (control). At the 3-month or 6-month follow-up, the animals underwent an open-chest electrophysiological study and were euthanized for histological analyses. No acute death occurred. Significant LV dysfunction was not seen. The surface ECG revealed a significant reduction in the P and QRS wave voltages in the radiation groups. The electrophysiological study showed that the local conduction times in each LV site were significantly longer and that the local LV bipolar voltages were significantly lower in the radiation groups than in the control rabbits. Histologically, apoptosis, fibrotic changes, and a decrease in the expression of the connexin 43 protein were seen in the LV myocardium. These changes were obvious at 3 months, and the effects were sustained 6 months after radiation. No histological changes were seen in the coronary artery and esophagus, but partial radiation pneumonitis was observed. Conclusions Medium-dose carbon ion and proton beam radiation in the whole LV resulted in a significant electrophysiological disturbance and pathological changes in the myocardium. Radiation of the arrhythmogenic substrate would modify the electrical status and potentially induce the antiarrhythmic effect.
Subject(s)
Electrophysiologic Techniques, Cardiac , Heart Ventricles , Heavy Ion Radiotherapy , Myocardium , Radiation Injuries, Experimental , Tachycardia, Ventricular , Ventricular Function, Left , Animals , Rabbits , Dose-Response Relationship, Radiation , Electrophysiologic Techniques, Cardiac/methods , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Heart Ventricles/radiation effects , Heavy Ion Radiotherapy/methods , Myocardium/pathology , Proton Therapy/methods , Radiation Injuries, Experimental/diagnosis , Radiation Injuries, Experimental/physiopathology , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/radiotherapy , Tomography, X-Ray Computed , Ventricular Function, Left/radiation effectsABSTRACT
PURPOSE: Radiation-induced cardiotoxicity is a significant concern in thoracic oncology patients. However, the basis for this disease pathology is not well characterized. We developed a novel mouse model of radiation-induced cardiotoxicity to investigate pathophysiologic mechanisms and identify clinically targetable biomarkers of cardiac injury. EXPERIMENTAL DESIGN: Single radiation doses of 20, 40, or 60 Gy were delivered to the cardiac apex of female C57BL/6 mice ages 9-11 weeks, with or without adjacent lung tissue, using conformal radiotherapy. Cardiac tissue was harvested up to 24 weeks post-radiotherapy for histologic analysis. Echocardiography and Technetium-99m sestamibi single photon emission computed tomography (SPECT) at 8 and 16 weeks post-radiotherapy were implemented to evaluate myocardial function and perfusion. Mouse cardiac tissue and mouse and human plasma were harvested for biochemical studies. RESULTS: Histopathologically, radiotherapy resulted in perivascular fibrosis 8 and 24 (P < 0.05) weeks post-radiotherapy. Apical perfusion deficits on SPECT and systolic and diastolic dysfunction on echocardiography 8 and 16 weeks post-radiotherapy were also observed (P < 0.05). Irradiated cardiac tissue and plasma showed significant increases in placental growth factor (PlGF), IL6, and TNFα compared with nonradiated matched controls, with greater increases in cardiac cytokine levels when radiotherapy involved lung. Human plasma showed increased PlGF (P = 0.021) and TNFα (P = 0.036) levels after thoracic radiotherapy. PlGF levels demonstrated a strong correlation (r = 0.89, P = 0.0001) with mean heart dose. CONCLUSIONS: We developed and characterized a pathophysiologically relevant mouse model of radiation-induced cardiotoxicity involving in situ irradiation of the cardiac apex. The model can be used to integrate radiomic and biochemical markers of cardiotoxicity to inform early therapeutic intervention and human translational studies.
Subject(s)
Heart/radiation effects , Myocardium/pathology , Radiation Injuries, Experimental/diagnosis , Animals , Biomarkers/analysis , Cardiotoxicity/diagnosis , Cardiotoxicity/etiology , Cardiotoxicity/pathology , Dose-Response Relationship, Radiation , Echocardiography , Female , Fibrosis , Heart/diagnostic imaging , Humans , Lung Neoplasms/radiotherapy , Mice , Radiation Injuries, Experimental/etiology , Radiation Injuries, Experimental/pathology , Tomography, Emission-Computed, Single-PhotonABSTRACT
Radiation damage of healthy tissues represents one of the complications of radiotherapy effectiveness. This study is focused on the screening of potentially effective drugs routinely used in medical practice and involved in the mechanism of radiation injury, namely for radiation-induced production of free radicals in the body. Experiments in rats revealed significant reduction of oxidative stress (malondialdehyde) and inflammatory marker (tumor necrosis factor α) in 10 Gy irradiated groups after administration of atorvastatin and a slight decrease after tadalafil administration, which indicates that one of the possible mechanisms for mitigation of radiation-induced cardiac damage could be the modulation of nitric oxide (NO) in endothelium and phosphodiesterase 5. In addition, miRNAs were analyzed as potential markers and therapeutically effective molecules. Expression of miRNA-21 and miRNA-15b showed the most significant changes after irradiation. Atorvastatin and tadalafil normalized changes of miRNA (miRNA-1, miRNA-15b, miRNA-21) expression levels in irradiated hearts. This screening study concludes that administration of specific drugs could mitigate the negative impact of radiation on the heart, but more detailed experiments oriented to other aspects of drug effectiveness and their exact mechanisms are still needed.
Subject(s)
Atorvastatin/administration & dosage , Cardiomyopathies/drug therapy , Heart/drug effects , Radiation Injuries, Experimental/drug therapy , Tadalafil/administration & dosage , Animals , Cardiomyopathies/blood , Cardiomyopathies/diagnosis , Cardiomyopathies/etiology , Free Radicals/blood , Free Radicals/metabolism , Gamma Rays/adverse effects , Heart/radiation effects , Male , Malondialdehyde/blood , Myocardium/metabolism , Myocardium/pathology , Oxidative Stress/drug effects , Oxidative Stress/radiation effects , Radiation Injuries, Experimental/blood , Radiation Injuries, Experimental/diagnosis , Radiation Injuries, Experimental/etiology , Rats , Treatment Outcome , Tumor Necrosis Factor-alpha/bloodABSTRACT
PURPOSE: Recent data have shown that single-fraction irradiation delivered to the whole brain in less than tenths of a second using FLASH radiotherapy (FLASH-RT), does not elicit neurocognitive deficits in mice. This observation has important clinical implications for the management of invasive and treatment-resistant brain tumors that involves relatively large irradiation volumes with high cytotoxic doses. EXPERIMENTAL DESIGN: Therefore, we aimed at simultaneously investigating the antitumor efficacy and neuroprotective benefits of FLASH-RT 1-month after exposure, using a well-characterized murine orthotopic glioblastoma model. As fractionated regimens of radiotherapy are the standard of care for glioblastoma treatment, we incorporated dose fractionation to simultaneously validate the neuroprotective effects and optimized tumor treatments with FLASH-RT. RESULTS: The capability of FLASH-RT to minimize the induction of radiation-induced brain toxicities has been attributed to the reduction of reactive oxygen species, casting some concern that this might translate to a possible loss of antitumor efficacy. Our study shows that FLASH and CONV-RT are isoefficient in delaying glioblastoma growth for all tested regimens. Furthermore, only FLASH-RT was found to significantly spare radiation-induced cognitive deficits in learning and memory in tumor-bearing animals after the delivery of large neurotoxic single dose or hypofractionated regimens. CONCLUSIONS: The present results show that FLASH-RT delivered with hypofractionated regimens is able to spare the normal brain from radiation-induced toxicities without compromising tumor cure. This exciting capability provides an initial framework for future clinical applications of FLASH-RT.See related commentary by Huang and Mendonca, p. 662.
Subject(s)
Brain Neoplasms/radiotherapy , Cognitive Dysfunction/prevention & control , Electrons/therapeutic use , Glioblastoma/radiotherapy , Radiation Injuries, Experimental/prevention & control , Animals , Brain/physiopathology , Brain/radiation effects , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Cognitive Dysfunction/physiopathology , Female , Humans , Mice , Organs at Risk/physiopathology , Organs at Risk/radiation effects , Radiation Dose Hypofractionation , Radiation Injuries, Experimental/diagnosis , Radiation Injuries, Experimental/etiology , Radiation Injuries, Experimental/physiopathology , Radiotherapy Dosage , Reactive Oxygen SpeciesABSTRACT
PURPOSE: We have evaluated the potential radioprotective, antioxidant and anti-apoptotic effects of resveratrol (RSV) against high-dose radioactive iodine (RAI) therapy associated damage of the lacrimal glands by biochemical, histopathological and immunohistochemical methods. MATERIALS AND METHODS: Thirty Wistar-albino rats were randomly divided into three groups; the control group received no treatment or medication, the RAI group received RAI but no medication and the RSV group received oral RAI and intraperitoneal RSV. RSV was started at day one, before RAI administration, and continued for 8 days. Bilateral intraorbital (IG), extraorbital (EG), and Harderian (HG) lacrimal glands were evaluated in all rats for histopathological, immunohistochemical, tissue cytokine and oxidant and antioxidant level assessment. RESULTS: RSV group restored inflammation, fibrosis, vacuolization, change in nucleus characteristics, lipofuscin-like accumulation and cellular morphologic patterns were statistically significant in all lacrimal gland types, compared to the RAI group (p < .05 for all variables). Similarly, elevated Caspase-3 and TUNEL levels in the RAI group were significantly alleviated in the RSV group in all lacrimal gland types (p < .05 for all variables). RAI administration significantly elevated TNF-α, IL-6, NF-кb levels, and decreased IL-10 levels (p < .05 for all parameters) whereas TOS levels significantly increased and TAS levels were significantly decreased. However, RSV significantly diminished TNF-α, IL-6, IL-4, and NF-кb levels. Furthermore, RSV significantly decreased TOS and increased TAS levels (p < .05 for all variables). CONCLUSIONS: We conclude that with its anti-cancer effect as well as its antioxidant effect RSV has protected the histopathological pattern of the lacrimal glands from the damage, decreased inflammation in histopathologic assessments, and decreased tissue cytokine levels, apoptosis and DNA fragmentation on the lacrimal glands after RAI.
Subject(s)
Iodine Radioisotopes/adverse effects , Lacrimal Apparatus Diseases/drug therapy , Lacrimal Apparatus/pathology , Radiation Injuries, Experimental/drug therapy , Resveratrol/pharmacology , Animals , Antioxidants/pharmacology , Disease Models, Animal , Female , Iodine Radioisotopes/therapeutic use , Lacrimal Apparatus/metabolism , Lacrimal Apparatus/radiation effects , Lacrimal Apparatus Diseases/diagnosis , Lacrimal Apparatus Diseases/etiology , Oxidative Stress , Radiation Injuries, Experimental/complications , Radiation Injuries, Experimental/diagnosis , Rats , Rats, WistarABSTRACT
Exposure to total- and partial-body irradiation following a nuclear or radiological incident result in the potentially lethal acute radiation syndromes of the gastrointestinal and hematopoietic systems in a dose- and time-dependent manner. Radiation-induced damage to the gastrointestinal tract is observed within days to weeks post-irradiation. Our objective in this study was to evaluate plasma biomarker utility for the gastrointestinal acute radiation syndrome in non-human primates after partial body irradiation with minimal bone marrow sparing through correlation with tissue and histological analyses. Plasma and jejunum samples from non-human primates exposed to partial body irradiation of 12 Gy with bone marrow sparing of 2.5% were evaluated at various time points from day 0 to day 21 as part of a natural history study. Additionally, longitudinal plasma samples from non-human primates exposed to 10 Gy partial body irradiation with 2.5% bone marrow sparing were evaluated at timepoints out to 180 d post-irradiation. Plasma and jejunum metabolites were quantified via liquid chromatography-tandem mass spectrometry and histological analysis consisted of corrected crypt number, an established metric to assess radiation-induced gastrointestinal damage. A positive correlation of metabolite levels in jejunum and plasma was observed for citrulline, serotonin, acylcarnitine, and multiple species of phosphatidylcholines. Citrulline levels also correlated with injury and regeneration of crypts in the small intestine. These results expand the characterization of the natural history of gastrointestinal acute radiation syndrome in non-human primates exposed to partial body irradiation with minimal bone marrow sparing and also provide additional data toward the correlation of citrulline with histological endpoints.
Subject(s)
Acute Radiation Syndrome/diagnosis , Biomarkers/blood , Bone Marrow/radiation effects , Gastrointestinal Tract/metabolism , Organ Sparing Treatments/methods , Radiation Exposure/adverse effects , Radiation Injuries, Experimental/diagnosis , Acute Radiation Syndrome/blood , Acute Radiation Syndrome/etiology , Animals , Citrulline/blood , Gastrointestinal Tract/radiation effects , Macaca mulatta , Male , Radiation Dosage , Radiation Injuries, Experimental/blood , Radiation Injuries, Experimental/etiologyABSTRACT
High-dose radiation exposure results in organ-specific sequelae that occurs in a time- and dose-dependent manner. The partial body irradiation with minimal bone marrow sparing model was developed to mimic intentional or accidental radiation exposures in humans where bone marrow sparing is likely and permits the concurrent analysis of coincident short- and long-term damage to organ systems. To help inform on the natural history of the radiation-induced injury of the partial body irradiation model, we quantitatively profiled the plasma proteome of non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing with 6 MV LINAC-derived photons at 0.80 Gy min over a time period of 3 wk. The plasma proteome was analyzed by liquid chromatography-tandem mass spectrometry. A number of trends were identified in the proteomic data including pronounced protein changes as well as protein changes that were consistently upregulated or downregulated at all time points and dose levels interrogated. Pathway and gene ontology analysis were performed; bioinformatic analysis revealed significant pathway and biological process perturbations post high-dose irradiation and shed light on underlying mechanisms of radiation damage. Additionally, proteins were identified that had the greatest potential to serve as biomarkers for radiation exposure.
Subject(s)
Acute Radiation Syndrome/diagnosis , Biomarkers/blood , Bone Marrow/radiation effects , Organ Sparing Treatments/methods , Proteome/analysis , Radiation Exposure/adverse effects , Radiation Injuries, Experimental/diagnosis , Acute Radiation Syndrome/blood , Acute Radiation Syndrome/etiology , Animals , Macaca mulatta , Male , Radiation Dosage , Radiation Injuries, Experimental/blood , Radiation Injuries, Experimental/etiologyABSTRACT
Exposure to ionizing radiation results in injuries of the hematopoietic, gastrointestinal, and respiratory systems, which are the leading causes responsible for morbidity and mortality. Gastrointestinal injury occurs as an acute radiation syndrome. To help inform on the natural history of the radiation-induced injury of the partial body irradiation model, we quantitatively profiled the proteome of jejunum from non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing over a time period of 3 wk. Jejunum was analyzed by liquid chromatography-tandem mass spectrometry, and pathway and gene ontology analysis were performed. A total of 3,245 unique proteins were quantified out of more than 3,700 proteins identified in this study. Also a total of 289 proteins of the quantified proteins showed significant and consistent responses across at least three time points post-irradiation, of which 263 proteins showed strong upregulations while 26 proteins showed downregulations. Bioinformatic analysis suggests significant pathway and upstream regulator perturbations post-high dose irradiation and shed light on underlying mechanisms of radiation damage. Canonical pathways altered by radiation included GP6 signaling pathway, acute phase response signaling, LXR/RXR activation, and intrinsic prothrombin activation pathway. Additionally, we observed dysregulation of proteins of the retinoid pathway and retinoic acid, an active metabolite of vitamin A, as quantified by liquid chromatography-tandem mass spectrometry. Correlation of changes in protein abundance with a well-characterized histological endpoint, corrected crypt number, was used to evaluate biomarker potential. These data further define the natural history of the gastrointestinal acute radiation syndrome in a non-human primate model of partial body irradiation with minimal bone marrow sparing.
Subject(s)
Acute Radiation Syndrome/diagnosis , Gastrointestinal Tract/metabolism , Organ Sparing Treatments/methods , Proteome/metabolism , Radiation Exposure/adverse effects , Radiation Injuries, Experimental/diagnosis , Retinoids/metabolism , Acute Radiation Syndrome/etiology , Acute Radiation Syndrome/metabolism , Animals , Biomarkers/metabolism , Bone Marrow/radiation effects , Disease Models, Animal , Gastrointestinal Tract/radiation effects , Macaca mulatta , Male , Proteome/analysis , Radiation Dosage , Radiation Injuries, Experimental/etiology , Radiation Injuries, Experimental/metabolismABSTRACT
Proton minibeams (MBs) comprised of parallel planar beamlets were evaluated for their ability to spare healthy brain compared to proton broad beams (BBs). Juvenile mice were given partial brain irradiation of 10 or 30 Gy integral dose using 100 MeV protons configured either as BBs or arrays of 0.3-mm planar MBs spaced 1.0 mm apart on center. Neurologic toxicity was evaluated during an 8-month surveillance: no overt constitutional or neurologic dysfunction was noted for any study animals. Less acute epilation was observed in MB than BB mice. Persistent chronic inflammation was noted along the entire BB path in BB mice whereas inflammation was confined to just within the MB peak regions in MB mice. The potential neurologic sparing, possibly via reduced volume of chronic inflammation, offers a compelling rationale for clinical advancement of this proton technique.
Subject(s)
Brain Neoplasms/radiotherapy , Brain/radiation effects , Organ Sparing Treatments/adverse effects , Proton Therapy/adverse effects , Radiation Injuries, Experimental/diagnosis , Animals , Behavior Observation Techniques , Behavior, Animal/radiation effects , Brain/pathology , Brain/physiopathology , Cognition/physiology , Cognition/radiation effects , Humans , Male , Mice , Neuropsychological Tests , Organ Sparing Treatments/instrumentation , Organ Sparing Treatments/methods , Pilot Projects , Proton Therapy/instrumentation , Proton Therapy/methods , Radiation Injuries, Experimental/etiology , Radiation Injuries, Experimental/pathology , Radiation Injuries, Experimental/physiopathology , Radiotherapy DosageSubject(s)
Neoplasms, Radiation-Induced/diagnosis , Neoplasms/radiotherapy , Radiation Injuries, Experimental/diagnosis , Radiation Injuries/diagnosis , Radiotherapy/methods , Animals , Humans , Neoplasms, Radiation-Induced/etiology , Neoplasms, Radiation-Induced/therapy , Nuclear Warfare/prevention & control , Radiation Effects , Radiation Injuries/prevention & control , Radiation Injuries/therapy , Radiation Injuries, Experimental/prevention & control , Radiotherapy/adverse effects , Research Personnel/statistics & numerical data , Risk Assessment , Risk FactorsABSTRACT
In a radiation exposure event, a likely scenario may include either total-body irradiation (TBI) or different partial-body irradiation (PBI) patterns. Knowledge of the exposure pattern is expected to improve prediction of clinical outcome. We examined miRNA species in 17 irradiated baboons receiving an upper-body, left hemibody or total-body irradiation of 2.5 or 5 Gy. Blood samples were taken before irradiation and at 1, 2, 7, 28 and 75-106 days after irradiation. Using a qRT-PCR platform for simultaneous detection of 667 miRNAs, we identified 55 miRNAs over all time points. Candidate miRNAs, such as miR-17, miR-128 or miR-15b, significantly discriminated TBI from different PBI exposure patterns, and 5-to-10-fold changes in gene expression were observed among the groups. A total of 22 miRNAs (including miR-17) revealed significant linear associations of gene expression changes with the percentage of the exposed body area (P < 0.0001). All these changes were primarily observed at day 7 postirradiation and almost no miRNAs were detected either before or after 7 days. A significant association in the reduction of lymphocyte counts in TBI compared to PBI animals corresponded with the number of miRNA candidates. This finding suggests that our target miRNAs predominantly originated from irradiated lymphocytes. In summary, gene expression changes in the peripheral blood provided indications of the exposure pattern and a suggestion of the percentage of the exposed body area.
Subject(s)
Lymphocytes/radiation effects , MicroRNAs/genetics , Radiation Exposure/adverse effects , Radiation Injuries, Experimental/blood , Whole-Body Irradiation/adverse effects , Animals , Gene Expression Profiling , Gene Expression Regulation , Male , Papio/genetics , Radiation Dosage , Radiation Injuries, Experimental/diagnosis , Radiation ProtectionSubject(s)
Acute Radiation Syndrome/etiology , Medical Countermeasures , Multiple Organ Failure/etiology , Radiation Injuries, Experimental/etiology , Acute Radiation Syndrome/diagnosis , Acute Radiation Syndrome/pathology , Acute Radiation Syndrome/therapy , Animals , Biomarkers , Macaca mulatta , Mice , Multiple Organ Failure/diagnosis , Multiple Organ Failure/pathology , Multiple Organ Failure/therapy , Radiation Injuries, Experimental/diagnosis , Radiation Injuries, Experimental/pathology , Radiation Injuries, Experimental/therapy , RatsSubject(s)
Acute Radiation Syndrome/therapy , Medical Countermeasures , Multiple Organ Failure/etiology , Radiation Injuries, Experimental/prevention & control , Radiation Injuries, Experimental/therapy , Acute Radiation Syndrome/diagnosis , Acute Radiation Syndrome/prevention & control , Animals , Biomarkers , Disease Models, Animal , Dose-Response Relationship, Radiation , Humans , Mice , Multiple Organ Failure/prevention & control , Multiple Organ Failure/therapy , Primates , Radiation Injuries, Experimental/diagnosis , Rats , Species SpecificityABSTRACT
Lesion and inactivation methods have played important roles in neuroscience studies. However, traditional techniques for creating a brain lesion are highly invasive, and control of lesion size and shape using these techniques is not easy. Here, we developed a novel method for creating a lesion on the cortical surface via 365 nm ultraviolet (UV) irradiation without breaking the dura mater. We demonstrated that 2.0 mWh UV irradiation, but not the same amount of non-UV light irradiation, induced an inverted bell-shaped lesion with neuronal loss and accumulation of glial cells. Moreover, the volume of the UV irradiation-induced lesion depended on the UV light exposure amount. We further succeeded in visualizing the lesioned site in a living animal using magnetic resonance imaging (MRI). Importantly, we also observed using an optical imaging technique that the spread of neural activation evoked by adjacent cortical stimulation disappeared only at the UV-irradiated site. In summary, UV irradiation can induce a focal brain lesion with a stable shape and size in a less invasive manner than traditional lesioning methods. This method is applicable to not only neuroscientific lesion experiments but also studies of the focal brain injury recovery process.
Subject(s)
Brain Injuries/etiology , Brain Injuries/pathology , Brain/pathology , Brain/radiation effects , Ultraviolet Rays/adverse effects , Animals , Brain/diagnostic imaging , Brain Injuries/diagnosis , Cell Count , Magnetic Resonance Imaging , Male , Nerve Degeneration/etiology , Nerve Degeneration/pathology , Neuroglia/pathology , Neuroglia/radiation effects , Organ Size , Radiation Injuries, Experimental/diagnosis , Radiation Injuries, Experimental/etiology , Radiation Injuries, Experimental/pathology , Rats , Rats, WistarABSTRACT
Light causes damage to the retina (phototoxicity) and decreases photoreceptor responses to light. The most harmful component of visible light is the blue wavelength (400-500 nm). Different filters have been tested, but so far all of them allow passing a lot of this wavelength (70%). The aim of this work has been to prove that a filter that removes 94% of the blue component may protect the function and morphology of the retina significantly. Three experimental groups were designed. The first group was unexposed to light, the second one was exposed and the third one was exposed and protected by a blue-blocking filter. Light damage was induced in young albino mice (p30) by exposing them to white light of high intensity (5,000 lux) continuously for 7 days. Short wavelength light filters were used for light protection. The blue component was removed (94%) from the light source by our filter. Electroretinographical recordings were performed before and after light damage. Changes in retinal structure were studied using immunohistochemistry, and TUNEL labeling. Also, cells in the outer nuclear layer were counted and compared among the three different groups. Functional visual responses were significantly more conserved in protected animals (with the blue-blocking filter) than in unprotected animals. Also, retinal structure was better kept and photoreceptor survival was greater in protected animals, these differences were significant in central areas of the retina. Still, functional and morphological responses were significantly lower in protected than in unexposed groups. In conclusion, this blue-blocking filter decreases significantly photoreceptor damage after exposure to high intensity light. Actually, our eyes are exposed for a very long time to high levels of blue light (screens, artificial light LED, neons ). The potential damage caused by blue light can be palliated.
Subject(s)
Eye Injuries/prevention & control , Light/adverse effects , Radiation Injuries, Experimental/prevention & control , Retina/radiation effects , Retinal Degeneration/prevention & control , Animals , Color , Electroretinography , Eye Injuries/diagnosis , Eye Injuries/etiology , In Situ Nick-End Labeling , Mice , Photoreceptor Cells, Vertebrate/radiation effects , Radiation Injuries, Experimental/diagnosis , Radiation Injuries, Experimental/etiology , Retina/cytology , Retina/injuries , Retinal Degeneration/etiologyABSTRACT
Skin tissue consists of collagen and elastic fibres, which are highly susceptible to damage when exposed to ultraviolet radiation (UVR), leading to skin aging and cancer. However, a lack of non-invasive detection methods makes determining the degree of UVR damage to skin in real time difficult. As one of the fundamental features of light, polarization can be used to develop imaging techniques capable of providing structural information about tissues. In particular, Mueller matrix polarimetry is suitable for detecting changes in collagen and elastic fibres. Here, we demonstrate a novel, quantitative, non-contact and in situ technique based on Mueller matrix polarimetry for monitoring the microstructural changes of skin tissues during UVR-induced photo-damaging. We measured the Mueller matrices of nude mouse skin samples, then analysed the transformed parameters to characterise microstructural changes during the skin photo-damaging and self-repairing processes. Comparisons between samples with and without the application of a sunscreen showed that the Mueller matrix-derived parameters are potential indicators for fibrous microstructure in skin tissues. Histological examination and Monte Carlo simulations confirmed the relationship between the Mueller matrix parameters and changes to fibrous structures. This technique paves the way for non-contact evaluation of skin structure in cosmetics and dermatological health.
Subject(s)
Diagnostic Imaging/methods , Models, Theoretical , Radiation Injuries, Experimental/diagnosis , Skin/metabolism , Animals , Collagen/metabolism , Elastic Tissue/metabolism , Humans , Mice , Mice, Nude , Microscopy, Polarization , Monte Carlo Method , Skin/pathology , Sunscreening Agents/administration & dosage , Ultraviolet Rays/adverse effects , Wound HealingABSTRACT
BACKGROUND: Although expander-based breast reconstruction is the most commonly used method of reconstruction worldwide, it continues to be plagued with complication rates as high as 60% when radiotherapy is implemented. We hypothesized that quantitative measures of radiotherapy-induced vascular injury can be mitigated by utilizing amifostine in a murine model of expander-based breast reconstruction. METHODS: 30 rats were divided into three groups: expander placement (Control), expander placement followed by radiotherapy (XRT), and expander placement followed by radiotherapy with amifostine (AMF/XRT). All groups underwent placement of a sub-latissimus tissue expander. After a 45 day recovery period, all groups underwent vascular perfusion and micro-CT analysis. RESULTS: Micro-CT analysis was used to calculate vessel volume fraction (VVF), vessel number (VN), and vessel separation (VSp). A significant increase in VN was seen in the XRT group as compared to the Control (p = 0.021) and the AMF/XRT (p = 0.027). There was no difference between Control and AMF/XRT (p = 0.862). VVF was significantly higher in XRT than either Control (p = 0.043) and AMF/XRT (p = 0.040), however no difference was seen between Control and AMF/XRT (p = 0.980). VSp of XRT was smaller when compared to both Control and AMF/XRT specimens (p = 0.05 and p = 0.048, respectively), and no difference was seen between Control and AMF/XRT (p = 0.339). CONCLUSIONS: Amifostine administered prior to radiotherapy preserved vascular metrics similar to those of non-radiated specimens. Elevated vascularity demonstrated within the XRT group was not seen in either the Control or AMF/XRT groups. These results indicate that amifostine protects soft tissue in our model from a radiotherapy-induced pathologic vascular response.
Subject(s)
Amifostine/administration & dosage , Breast Neoplasms/radiotherapy , Mammaplasty/methods , Mammary Arteries/pathology , Neoplasms, Experimental , Radiation Injuries, Experimental/prevention & control , Tissue Expansion Devices , Angiography , Animals , Breast Neoplasms/blood supply , Breast Neoplasms/surgery , Disease Models, Animal , Dose-Response Relationship, Drug , Imaging, Three-Dimensional , Male , Mammary Arteries/drug effects , Mammary Arteries/radiation effects , Radiation Injuries, Experimental/diagnosis , Radiation-Protective Agents/administration & dosage , Rats , Rats, Sprague-DawleyABSTRACT
In case of a mass casualty radiation event, there is a need to distinguish total-body irradiation (TBI) and partial-body irradiation (PBI) to concentrate overwhelmed medical resources to the individuals that would develop an acute radiation syndrome (ARS) and need hematologic support (i.e., mostly TBI victims). To improve the identification and medical care of TBI versus PBI individuals, reliable biomarkers of exposure could be very useful. To investigate this issue, pairs of baboons (n = 18) were exposed to different situations of TBI and PBI corresponding to an equivalent of either 5 Gy 60Co gamma irradiation (5 Gy TBI; 7.5 Gy left hemibody/2.5 right hemibody TBI; 5.55 Gy 90% PBI; 6.25 Gy 80% PBI; 10 Gy 50% PBI, 15 Gy 30% PBI) or 2.5 Gy (2.5 Gy TBI; 5 Gy 50% PBI). More than fifty parameters were evaluated before and after irradiation at several time points up to 200 days. A partial least square discriminant analysis showed a good distinction of TBI from PBI situations that were equivalent to 5 Gy. Furthermore, all the animals were pooled in two groups, TBI (n = 6) and PBI (n = 12), for comparison using a logistic regression and a non parametric statistical test. Nine plasmatic biochemical markers and most of hematological parameters turned out to discriminate between TBI and PBI animals during the prodromal phase and the manifest illness phase. The most significant biomarkers were aspartate aminotransferase, creatine kinase, lactico dehydrogenase, urea, Flt3-ligand, iron, C-reactive protein, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the early period, and Flt3-ligand, iron, platelet count, hemoglobin, monocyte count, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the ARS phase. These results suggest that heterogeneity could be distinguished within a range of 2.5 to 5 Gy TBI.
Subject(s)
Biomarkers/blood , Models, Animal , Radiation Injuries, Experimental/blood , Whole-Body Irradiation/methods , Animals , Aspartate Aminotransferases/blood , C-Reactive Protein/metabolism , Creatine Kinase/blood , Gamma Rays , Humans , Iron/blood , Leukocyte Count , Male , Membrane Proteins/blood , Papio , Radiation Dosage , Radiation Injuries, Experimental/diagnosis , Radiation Injuries, Experimental/etiology , Radiation Monitoring/instrumentation , Radiation Monitoring/methods , Reproducibility of Results , Sensitivity and Specificity , Urea/blood , Whole-Body Irradiation/adverse effectsABSTRACT
PURPOSE: This study is an investigation of the relationship between several characteristic parameters and acute thermal damage in porcine skeletal muscle. MATERIAL AND METHODS: Fourteen pigs under injection anaesthesia were placed into a magnetic resonance body coil and exposed for different time durations to different specific energy absorption rate (SAR) levels at 123 MHz. Local temperatures were measured using four temperature sensors. Sensors 1-3 were placed in skeletal muscle and one sensor was placed in the rectum. Sensors 1 and 2 were placed in hot-spot areas and sensor 3 was placed at the periphery of the animals. The pigs were exposed to whole-body SAR (SAR-wb) between 2.5 W/kg and 5.2 W/kg for 30 or 60 min. Three animals received no SAR. After each experiment, muscle samples adjacent to the positions of sensors 1-3 were taken for frozen section analysis. Three characteristic parameters were chosen for investigation: SAR-wb, maximum sensor temperature (T-max), and cumulative equivalent minutes at 43 °C (CEM43 °C). RESULTS: Histopathological criteria were established to detect acute thermal tissue damage in frozen sections such as widening of intercellular space between the muscle fibres and loss of glycogen. Clear tissue damage thresholds were found for T-max and CEM43 °C, though not for SAR-wb. For all animals with high thermal exposure, damage was also found for muscle samples adjacent to the peripheral sensor 3. CONCLUSIONS: Both T-max and CEM43, are able to predict thermal damage in porcine muscle. However, CEM43 is the less ambiguous parameter. The reasons for the occurrence of the aforementioned damage at low local temperatures at the animals' periphery remain unclear and further investigations are needed.