scholarly journals Metformin Protects against Radiation-Induced Pneumonitis and Fibrosis and Attenuates Upregulation of Dual Oxidase Genes Expression

2018 ◽  
Vol 8 (4) ◽  
pp. 697-704 ◽  
Author(s):  
Rasoul Azmoonfar ◽  
Peyman Amini ◽  
Hana Saffar ◽  
Saeed Rezapoor ◽  
Elahe Motevaseli ◽  
...  

Purpose: Lung tissue is one of the most sensitive organs to ionizing radiation (IR). Early and late side effects of exposure to IR can limit the radiation doses delivered to tumors that are within or adjacent to this organ. Pneumonitis and fibrosis are the main side effects of radiotherapy for this organ. IL-4 and IL-13 have a key role in the development of pneumonitis and fibrosis. Metformin is a potent anti-fibrosis and redox modulatory agent that has shown radioprotective effects. In this study, we aimed to evaluate possible upregulation of these cytokines and subsequent cascades such as IL4-R1, IL-13R1, Dual oxidase 1 (DUOX1) and DUOX2. In addition, we examined the potential protective effect of metformin in these cytokines and genes, as well as histopathological changes in rat’s lung tissues. Methods: 20 rats were divided into 4 groups: control; metformin treated; radiation + metformin; and radiation. Irradiation was performed with a 60Co source delivering 15 Gray (Gy) to the chest area. After 10 weeks, rats were sacrificed and their lung tissues were removed for histopathological, real-time PCR and ELISA assays. Results: Irradiation of lung was associated with an increase in IL-4 cytokine level, as well as the expression of IL-4 receptor-a1 (IL4ra1) and DUOX2 genes. However, there was no change in the level of IL-13 and its downstream gene including IL-13 receptor-a2 (IL13ra2). Moreover, histopathological evaluations showed significant infiltration of lymphocytes and macrophages, fibrosis, as well as vascular and alveolar damages. Treatment with metformin caused suppression of upregulated genes and IL-4 cytokine level, associated with amelioration of pathological changes. Conclusion: Results of this study showed remarkable pathological damages, an increase in the levels of IL-4, IL4Ra1 and Duox2, while that of IL-13 decreased. Treatment with metformin showed ability to attenuate upregulation of IL-4–DUOX2 pathway and other pathological damages to the lung after exposure to a high dose of IR.

Nukleonika ◽  
2014 ◽  
Vol 59 (1) ◽  
pp. 9-13
Author(s):  
Ahmed M. Maghraby ◽  
A. Mansour ◽  
A. A. Abdel-Fattah

Abstract Taurine/EPR rods (3 × 10 mm) have been prepared by a simple technique in the laboratory where taurine powder was mixed with a molten mixture of paraffin wax and an ethylene vinyl acetate (EVA) copolymer. The binding mixture EVA/Paraffin does not present interference or noise in the EPR signal before or after irradiation. The rods show good mechanical properties for safe and multi-use handling. An EPR investigation of radiation induced radicals in taurine rods revealed that there are two types of radicals produced after exposure to gamma radiation (60Co). EPR spectra were recorded and analyzed - also the microwave power saturation and modulation amplitude were studied and optimized. Response of taurine to different radiation doses (1.5-100 kGy) was studied and found to follow a linear relationship up to 100 kGy. Radiation induced radicals in taurine persists and showed a noticeable stability over 94 days following irradiation. Uncertainities associated with the evaluation of radiation doses using taurine dosimeters were discussed and tabulated. It was found that taurine possesses good dosimetric properties using EPR spectroscopy in high doses in addition to its simple spectrum.


2019 ◽  
Vol 12 (1) ◽  
pp. 23-28 ◽  
Author(s):  
Sedighe Kolivand ◽  
Peyman Amini ◽  
Hana Saffar ◽  
Saeed Rezapoor ◽  
Elahe Motevaseli ◽  
...  

Background: Heart injury is one of the most important concerns after exposure to a high dose of radiation in chest cancer radiotherapy or whole body exposure to a radiation disaster. Studies have proposed that increased level of inflammatory and pro-fibrotic cytokines following radiotherapy or radiation events play a key role in the development of several side effects such as cardiovascular disorders. In the current study, we aimed to evaluate the expression of IL-4 and IL-13 cytokines as well as signaling pathways such as IL4Ra1, IL13Ra2, Duox1 and Duox2. In addition, we detected the possible protective effect of curcumin on the expression of these factors and infiltration of inflammatory cells. Materials and Methods: Twenty rats were divided into 4 groups including control; curcumin treated; radiation; and radiation plus curcumin. After 10 weeks, rats were sacrificed for evaluation of mentioned parameters. Results: Results showed an increase in the level of IL-4 and all evaluated genes, as well as increased infiltration of lymphocytes and macrophages. Treatment with curcumin could attenuate these changes. Conclusion: Curcumin could reduce radiation-induced heart injury markers in rats.


2019 ◽  
Vol 12 (11) ◽  
pp. e230700 ◽  
Author(s):  
Bassel Hallak ◽  
Miranda Morrison ◽  
Romain Kohler ◽  
Salim Bouayed

Nasopharyngeal carcinoma (NPC), an uncommon malignancy in Western Countries and Radiotherapy, remains an effective treatment. Its side effects are classified as either immediate or late; postradiation necrosis is as an important late side effect with a strong impact on the prognosis in patients with NPC. We report the case of 65-year-old Caucasian man presenting with a deep necrotic ulcer of the nasopharynx and osteoradionecrosis of the skull base that appeared 3 months after radiotherapy for nasopharyngeal carcinoma. Conservative treatment was applied with surgical management of the ulcer. Clinical and radiological outcomes are presented. Radiotherapy remains a good treatment option with varying degrees of side effects, in particular, postradiation necrosis and ulcer. Multiple options of treatment have been described. However, the surgical management could be indicated in cases of deep ulcer with life-threatening prognosis.


1988 ◽  
Vol 27 (06) ◽  
pp. 266-271
Author(s):  
J. Ruhlmann ◽  
B. Ammari ◽  
R. Knopp ◽  
A. Hotze ◽  
H.-J. Biersack ◽  
...  

Three patients with pulmonary metastases from differentiated thyroid carcinoma were treated with radioiodine. As a first treatment either 1.85 GBq (50 mCi) or 3.7 GBq (100 mCi) were given followed by doses of 11.1 GBq (300 mCi)131I. In one patient the pulmonary metastases disappeared completely, the two other patients showed a significant regression. In one patient possibly radiation-induced pancytopenic changes appeared after the third and fourth radioiodine treatment, in the other two patients side-effects were not seen.


2019 ◽  
Vol 195 (11) ◽  
pp. 972-981 ◽  
Author(s):  
Radovan Vojtíšek ◽  
Emília Sukovská ◽  
Jan Baxa ◽  
Marie Budíková ◽  
Petra Kovářová ◽  
...  

2004 ◽  
Vol 60 (3) ◽  
pp. 871-878 ◽  
Author(s):  
Quoc-Chuong Bui ◽  
Michael Lieber ◽  
H.Rodney Withers ◽  
Kevan Corson ◽  
Marius van Rijnsoever ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1671 ◽  
Author(s):  
Yasaman Alaghband ◽  
Samantha N. Cheeks ◽  
Barrett D. Allen ◽  
Pierre Montay-Gruel ◽  
Ngoc-Lien Doan ◽  
...  

Major advances in high precision treatment delivery and imaging have greatly improved the tolerance of radiotherapy (RT); however, the selective sparing of normal tissue and the reduction of neurocognitive side effects from radiation-induced toxicities remain significant problems for pediatric patients with brain tumors. While the overall survival of pediatric patients afflicted with medulloblastoma (MB), the most common type primary brain cancer in children, remains high (≥80%), lifelong neurotoxic side-effects are commonplace and adversely impact patients’ quality of life. To circumvent these clinical complications, we have investigated the capability of ultra-high dose rate FLASH-radiotherapy (FLASH-RT) to protect the radiosensitive juvenile mouse brain from normal tissue toxicities. Compared to conventional dose rate (CONV) irradiation, FLASH-RT was found to ameliorate radiation-induced cognitive dysfunction in multiple independent behavioral paradigms, preserve developing and mature neurons, minimize microgliosis and limit the reduction of the plasmatic level of growth hormone. The protective “FLASH effect” was pronounced, especially since a similar whole brain dose of 8 Gy delivered with CONV-RT caused marked reductions in multiple indices of behavioral performance (objects in updated location, novel object recognition, fear extinction, light-dark box, social interaction), reductions in the number of immature (doublecortin+) and mature (NeuN+) neurons and increased neuroinflammation, adverse effects that were not found with FLASH-RT. Our data point to a potentially innovative treatment modality that is able to spare, if not prevent, many of the side effects associated with long-term treatment that disrupt the long-term cognitive and emotional well-being of medulloblastoma survivors.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18576-18576
Author(s):  
M. Inbar ◽  
D. Grisaru ◽  
G. Fishlev ◽  
J. Lessing ◽  
R. Almog ◽  
...  

18576 Background: The treatment of pelvic malignancies (uterine, cervix, rectum, etc) often include radiation. Radiation-induced late side effects (longer than 3 months) are developed in 5–10% of those patients. We wanted to investigate the efficacy of hyperbaric oxygen therapy (HBOT) in the management of those patients. Methods: Thirteen women were evaluated. The primary cancer sources were: cervix (7), vagina (2), uterus (2), rectum (1) and bladder (1). All patients were treated with a full pelvic dose of radiotherapy. Eight patients also underwent post-radiation surgery (4 post-hysterectomy, 1 post-colectomy, 1 post-vaginectomy, 1 post-cystectomy and 1 post-exanteration). Eleven patients suffered from pelvic pain, 7 from chronic cystitis (including 2 with vesico-vaginal fistulas), 7 had chronic proctitis (including 2 with recto-vaginal fistulas), 3 had long-standing vaginal ulcers, and one presented with a long-standing open skin wound following surgery. All patients underwent imaging studies and biopsies to rule out active malignant disease, and all received HBOT 100% oxygen, at 2 absolute atmospheres, for 90 minutes (2ATA 90 min). Results: The mean patient age was 61 years (range 32–88). The mean time between completion of radiation therapy and onset of symptoms was 32 months (range 4–60). The patients received an average of 27 HBOTs (range 16–40). Twelve patients reported improvement in pelvic pain, bladder and bowel symptoms and decrease in vaginal discharge. One patient developed lung metastasis and another developed pelvic recurrence. No patient reported side effects associated with HBOT. Conclusion: HBOT appears to be safe and effective in the management of pelvic radiation-induced late side effects, such as soft tissue necrosis (skin and vagina), cystitis, proctitis and fistulas. No significant financial relationships to disclose.


2019 ◽  
Vol 7 (2A) ◽  
Author(s):  
Leticia Bonfim ◽  
Luma Ramirez de Carvalho ◽  
Daniel Perez Vieira

Micronucleus assay is a test used to evaluate genotoxic damage in cells, which can be caused by various factors, like ionizing radiation. Interactions between radiation energies and DNA can cause breakage, leading to use chromosomal mutations or loss of genetic material, important events that could be induced in solid tumors to mitigate its expansion within human body.  Melanoma has been described as a tumor with increased radio resistance.  This work evaluated micronuclei percentages (%MN) in human melanoma cells (SK-MEL-37), irradiated by gamma radiation, with doses between 0 and 16Gy.  Cell suspensions were irradiated in PBS by a 60Co source in doses between 0 and 16Gy, and incubated by 48h.  Then cell membranes were lysed in the presence of SYTOX Green and EMA dyes, preserving nuclear membranes.  Using this method, EMA-stained nuclei could be discriminated as those derived from dead cells, and SYTOX nuclei and micronuclei could be quantified.  Micronuclei percentages were found to be proportional to dose, (R2 = 0.997).  Only the highest dose (16Gy) could induce statistically significant increase of MN (p<0.0001), although cultures irradiated by 4, 8 and 16Gy showed significant increase of dead cell fractions.  Calculation of the nuclei-to-beads ratio showed that 8 and 16Gy could reduce melanoma cell proliferation.  Results showed that although cell death and loss of proliferative capacity could be observed on cultures irradiated at lower doses, genotoxic damage could be induced only on a higher dose. Resistance to radiation-induced genotoxicity could explain a relatively high radio resistance of melanoma tumors.


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