scholarly journals Sphingosine-1-phosphate and its mimetic FTY720 do not protect against radiation-induced ovarian fibrosis in the nonhuman primate

2021 ◽  
Author(s):  
Farners Amargant ◽  
Sharrón L Manuel ◽  
Megan J Larmore ◽  
Brian W Johnson ◽  
Maralee Lawson ◽  
...  
Keyword(s):  
Late Effects ◽  
Rhesus Macaques ◽  
Tunica Albuginea ◽  
Ovarian Follicle ◽  
Protein Assay ◽  
Ovarian Stroma ◽  
Sphingosine 1 Phosphate ◽  
Radiation Induced ◽  
Effects Of Radiation ◽  
Long Acting

Abstract Oocytes are highly radiosensitive, so agents that prevent radiation-induced ovarian follicle destruction are important fertility preservation strategies. A previous study in rhesus macaques demonstrated that ovarian treatment with anti-apoptotic agents, sphingosine-1-phosphate (S1P) and FTY720, its long-acting mimetic, preserved follicles following a single dose of 15 Gy X-ray radiation, and live offspring were obtained from FTY720-treated animals. However, it is unknown whether these anti-apoptotic agents also protected the ovarian stroma from late effects of radiation, including vascular damage and fibrosis. Using ovarian histological sections from this study, we evaluated the vasculature and extracellular matrix in the following cohorts: vehicle + sham irradiation, vehicle + irradiation (OXI), S1P + irradiation (S1P), and FTY720 + irradiation (FTY720). One ovary from each animal was harvested prior to radiation whereas the contralateral ovary was harvested 10 months post-treatment. We assessed vasculature by immunohistochemistry with a PECAM1 antibody, hyaluronan by a hyaluronan binding protein assay, and collagen by picrosirius red and Masson’s trichrome staining. Disorganized vessels were observed in the medulla in the OXI and S1P cohorts relative to the sham, but the vasculature in the FTY720 cohort appeared intact, which may partially explain fertoprotection. There were no differences in the hyaluronan matrix among the cohorts, but there was thickening of the tunica albuginea and fibrosis in the OXI cohort relative to the sham, which was not mitigated by either S1P or FTY720 treatment. Thus, the fertoprotective properties of S1P and FTY720 may be limited given their inability to protect the ovarian stroma against the late effects of radiation-induced fibrosis.

scholarly journals Radiation-Induced Dual Oxidase Upregulation in Rat Heart Tissues: Protective Effect of Melatonin

Medicina ◽  
2019 ◽  
Vol 55 (7) ◽  
pp. 317 ◽  
Author(s):  
Farhood ◽  
Aliasgharzadeh ◽  
Amini ◽  
Saffar ◽  
Motevaseli ◽  
...  
Keyword(s):  
Late Effects ◽  
Background Radiation ◽  
Inflammatory Cells ◽  
Chronic Oxidative Stress ◽  
Increased Risk ◽  
Male Wistar Rats ◽  
Radiation Induced ◽  
Heart Injury ◽  
Chest Irradiation ◽  
Effects Of Radiation

Background: Radiation-induced heart injury can lead to increased risk of heart failure, attack, and ischemia. Some studies proposed IL-4 and IL-13 as two important cytokines that are involved in late effects of ionizing radiation. On the other hand, these cytokines may, through upregulation of Duox1 and Duox2, induce chronic oxidative stress, inflammation, and fibrosis. In this study, we evaluated the upregulation of Duox1 and Duox2 pathways in hearts following chest irradiation in rats and then detected possible attenuation of them by melatonin. Materials and Methods: Twenty male Wistar rats were divided into four groups: (1) control; (2) melatonin treated (100 mg/kg); (3) radiation (15 Gy gamma rays); (4) melatonin treated before irradiation. All rats were sacrificed after 10 weeks and their heart tissues collected for real-time PCR (RT-PCR), ELISA detection of IL-4 and IL-13, as well as histopathological evaluation of macrophages and lymphocytes infiltration. Results: Results showed an upregulation of IL-4, IL4ra1, Duox1, and Duox2. The biggest changes were for IL4ra1 and Duox1. Treatment with melatonin before irradiation could attenuate the upregulation of all genes. Melatonin also caused a reduction in IL-4 as well as reverse infiltration of inflammatory cells. Conclusion: Duox1 and Duox2 may be involved in the late effects of radiation-induced heart injury. Also, via attenuation of these genes, melatonin can offer protection against the toxic effects of radiation on the heart.

scholarly journals Radiation-induced ovarian follicle loss occurs without overt stromal changes

Reproduction ◽  
2018 ◽  
Vol 155 (6) ◽  
pp. 553-562 ◽  
Author(s):  
Bruce F Kimler ◽  
Shawn M Briley ◽  
Brian W Johnson ◽  
Austin G Armstrong ◽  
Susmita Jasti ◽  
...  
Keyword(s):  
Low Dose ◽  
Ovarian Tissue ◽  
Ovarian Follicle ◽  
Ovarian Follicles ◽  
Specific Protein ◽  
Reproductive Aging ◽  
Ovarian Stroma ◽  
Cesium 137 ◽  
Radiation Induced ◽  
Total Body

Radiation damage due to total body irradiation (TBI) or targeted abdominal radiation can deplete ovarian follicles and accelerate reproductive aging. We characterized a mouse model of low-dose TBI to investigate how radiation affects the follicular and stromal compartments of the ovary. A single TBI dose of either 0.1 Gy or 1 Gy (Cesium-137 γ) was delivered to reproductively adult CD1 female mice, and sham-treated mice served as controls. Mice were euthanized either 2 weeks or 5 weeks post exposure, and ovarian tissue was harvested. To assess the ovarian reserve, we classified and counted the number of morphologically normal follicles in ovarian histologic sections for all experimental cohorts using an objective method based on immunohistochemistry for an oocyte-specific protein (MSY2). 0.1 Gy did not affect that total number of ovarian follicles, whereas 1 Gy resulted in a dramatic loss. At two weeks, there was a significant reduction in all preantral follicles, but early antral and antral follicles were still present. By five weeks, there was complete depletion of all follicle classes. We examined stromal quality using histologic stains to visualize ovarian architecture and fibrosis and by immunohistochemistry and quantitative microscopy to assess cell proliferation, cell death and vasculature. There were no differences in the ovarian stroma across cohorts with respect to these markers, indicating that this compartment is more radio-resistant relative to the germ cells. These findings have implications for reproductive health and the field of fertility preservation because the radiation doses we examined mimic scatter doses experienced in typical therapeutic regimens.

scholarly journals Plasma Derived Exosomal Biomarkers of Exposure to Ionizing Radiation in Nonhuman Primates

2018 ◽  
Vol 19 (11) ◽  
pp. 3427 ◽  
Author(s):  
Amrita Cheema ◽  
Charles Hinzman ◽  
Khyati Mehta ◽  
Briana Hanlon ◽  
Melissa Garcia ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Nonhuman Primates ◽  
Rhesus Macaques ◽  
Ultra Performance Liquid Chromatography ◽  
Molecular Signature ◽  
Detection And Identification ◽  
Molecular Events ◽  
Plasma Metabolome ◽  
Radiation Induced ◽  
Hydroxyl Fatty Acids

Exposure to ionizing radiation induces a cascade of molecular events that ultimately impact endogenous metabolism. Qualitative and quantitative characterization of metabolomic profiles is a pragmatic approach to studying the risks of radiation exposure since it provides a phenotypic readout. Studies were conducted in irradiated nonhuman primates (NHP) to investigate metabolic changes in plasma and plasma-derived exosomes. Specifically, rhesus macaques (Macaca mulatta) were exposed to cobalt-60 gamma-radiation and plasma samples were collected prior to and after exposure to 5.8 Gy or 6.5 Gy radiation. Exosomes were isolated using ultracentrifugation and analyzed by untargeted profiling via ultra-performance liquid chromatography mass spectrometry (UPLC-MS) based metabolomic and lipidomic analyses, with the goal of identifying a molecular signature of irradiation. The enrichment of an exosomal fraction was confirmed using quantitative ELISA. Plasma profiling showed markers of dyslipidemia, inflammation and oxidative stress post-irradiation. Exosomal profiling, on the other hand, enabled detection and identification of low abundance metabolites that comprise exosomal cargo which would otherwise get obscured with plasma profiling. We discovered enrichment of different classes of metabolites including N-acyl-amino acids, Fatty Acid ester of Hydroxyl Fatty Acids (FAHFA’s), glycolipids and triglycerides as compared to the plasma metabolome composition with implications in mediation of systemic response to radiation induced stress signaling.

Oral Sequelae of Head and Neck Radiotherapy

2003 ◽  
Vol 14 (3) ◽  
pp. 199-212 ◽  
Author(s):  
A. Vissink ◽  
J. Jansma ◽  
F.K.L. Spijkervet ◽  
F.R. Burlage ◽  
R.P. Coppes
Keyword(s):  
Head And Neck ◽  
Neck Region ◽  
Normal Tissues ◽  
Radiation Caries ◽  
Temporomandibular Joints ◽  
Clinical Consequences ◽  
Radiation Induced ◽  
Heavy Burden ◽  
Effects Of Radiation ◽  
Induced Changes

In addition to anti-tumor effects, ionizing radiation causes damage in normal tissues located in the radiation portals. Oral complications of radiotherapy in the head and neck region are the result of the deleterious effects of radiation on, e.g., salivary glands, oral mucosa, bone, dentition, masticatory musculature, and temporomandibular joints. The clinical consequences of radiotherapy include mucositis, hyposalivation, taste loss, osteoradionecrosis, radiation caries, and trismus. Mucositis and taste loss are reversible consequences that usually subside early post-irradiation, while hyposalivation is normally irreversible. Furthermore, the risk of developing radiation caries and osteoradionecrosis is a life-long threat. All these consequences form a heavy burden for the patients and have a tremendous impact on their quality of life during and after radiotherapy. In this review, the radiation-induced changes in healthy oral tissues and the resulting clinical consequences are discussed.

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