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Uyan M, Yilmaz H, Tümkaya L, Suzan ZT, Mercantepe T. Radioprotective effects of coenzyme Q10 on X-ray radiation-induced intestinal damage via oxidative stress and apoptosis. Arch Med Res 2025; 56:103181. [PMID: 39862484 DOI: 10.1016/j.arcmed.2025.103181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 10/30/2024] [Accepted: 01/15/2025] [Indexed: 01/27/2025]
Abstract
AIM The World Health Organization reported that cancer was the cause of death for 9.7 million people in 2022, and the numbers continue to rise every day. The present study examines the potential radioprotective effects of ubiquinone against x-ray radiation-induced intestinal damage and offers insight into new near-future methods for the treatment of radiation-induced tissue toxicity. MATERIALS AND METHODS Thirty-two male Sprague-Dawley rats were randomly divided into four groups. Group I (control) received no treatment during the experiment; Group II (IR [a single dose of 2 Gy pelvic/abdominal ionizing radiation]) received radiation only; Group III (a low dose of CoQ10 [30 mg/kg CoQ10 by oral gavage for 7 d] + IR) and Group IV (a high dose of CoQ10 [150 mg/kg CoQ10 by oral gavage for 7 d] + IR). The rats were sacrificed 24 h after x-ray radiation, and tissues were collected from the small intestine and subjected to histochemical analysis. RESULTS Diffuse villous fusion, enterocyte loss, hemorrhagic areas, inflammation, and fibrosis were observed in the IR group, as well as an increase in apoptotic enterocytes. In contrast, a decrease was observed in the IR+LD-CoQ10 and IR+HD-CoQ10 groups, along with a decrease, especially in villous fusion and enterocyte loss, hemorrhagic areas, inflammation, and fibrosis. CONCLUSION CoQ10 was found to reduce duodenal damage, oxidative stress, and apoptosis induced by x-ray radiation exposure and had a radioprotective effect.
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Affiliation(s)
- Mikail Uyan
- Departments of General Surgery, Recep Tayyip Erdogan University, Rize, Turkey
| | - Hamit Yilmaz
- Biophysics, Recep Tayyip Erdogan University, Rize, Turkey.
| | - Levent Tümkaya
- Histology and Embryology, Recep Tayyip Erdogan University, Rize, Turkey
| | - Zehra Topal Suzan
- Histology and Embryology, Recep Tayyip Erdogan University, Rize, Turkey
| | - Tolga Mercantepe
- Histology and Embryology, Recep Tayyip Erdogan University, Rize, Turkey
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Li Y, Wu X, Pei Y, Wang Z, Wang C, Hua D. Recent advances on macromolecular medicinal materials for radioprotection. J Drug Deliv Sci Technol 2023. [DOI: 10.1016/j.jddst.2023.104224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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Javadi A, Nikhbakht MR, Ghasemian Yadegari J, Rustamzadeh A, Mohammadi M, Shirazinejad A, Azadbakht S, Abdi Z. In-vivo and in vitro assessments of the radioprotective potential natural and chemical compounds: a review. Int J Radiat Biol 2023; 99:155-165. [PMID: 35549605 DOI: 10.1080/09553002.2022.2078007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
PURPOSE The study of the radioactive role of natural and chemical substances on human and animal studies has been the subject of research by some researchers. Therefore, the review of some of the past and current studies conducted in this field, can provide helpful information to elucidate of the importance of radioprotective components in reducing radiation exposure side effects. METHODS The authors search for keywords including In vitro, In vivo, Radioprotective, Ionizing radiation, and Vitamin in ScienceDirect, Scopus, Pubmed, and Google Scholar databases to access previously published articles and search for more reference articles on the role of radioprotective materials from natural and chemical compounds. RESULTS Radiation exposure can produce reactive oxygen species (ROS) in the body, however most of which are eliminated by the body's natural mechanisms, but when the body's antioxidant systems do not have enough ability to neutralize free radicals, oxidative stress occurs, which causes damage to DNA and body tissues. Therefore, it is necessary use of alternative substances that reduce and inhibit free radicals. CONCLUSION In general, recommended that antioxidant component(s) can be protect tissue damages in humans or animals, due to the their ability to scavenge free radicals generated by ionizing radiation.
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Affiliation(s)
- Anis Javadi
- Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Mohammad Reza Nikhbakht
- Department of Physiology and Pharmacology, School of Medicine Medicinal Plants Research Center Yasuj, University of Medical Sciences, Yasuj, Iran
| | - Javad Ghasemian Yadegari
- Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Auob Rustamzadeh
- Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohsen Mohammadi
- Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran.,Hepatitis Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran.,Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Alireza Shirazinejad
- Department of Food Science and Technology, Sarvestan Branch, Islamic Azad University, Sarvestan, Iran
| | - Saleh Azadbakht
- Department of Internal Medicine, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Zahra Abdi
- Department of Medical Biotechnology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
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Zhang T, Shi L, Xu Y, Li Y, Li S, Guan B, Qi Z, Zhang Y, Liu L. Purified PEGylated human glucagon-like peptide-2 reduces the severity of irradiation-induced acute radiation enteritis in rats. JOURNAL OF RADIATION RESEARCH 2019; 60:7-16. [PMID: 30247656 PMCID: PMC6373673 DOI: 10.1093/jrr/rry076] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 05/08/2018] [Indexed: 06/08/2023]
Abstract
Radiation-induced acute intestinal injury after abdominal and pelvic irradiation is a common and serious problem in the clinical setting. Glucagon-like peptide-2 (GLP-2), a 33-amino acid peptide, exerts diverse effects related to the regulation of gastrointestinal growth and function. However, GLP-2 is relatively unstable in vivo. The aim of the present study was to improve GLP-2 stability in vivo and to evaluate its therapeutic effect on acute radiation enteritis. We generated long-lasting intestinal protection peptides by conjugating human GLP-2 (hGLP-2) peptides to polyethyleneglycol (PEG) to produce mPEGylation hGLP-2 (Mono-PEG-hGLP-2) through an enzymatic site-specific transglutamination reaction. Mono-PEG-hGLP-2 synthesized under optimal reaction conditions and separated by one-step ion-exchange chromatography was found to be resistant to degradation in vitro. Pretreatment with Mono-PEG-hGLP-2 reduced the severity of radiation-induced intestinal injury, oxidative stress, and the expression of NF-κB in rats with irradiation-induced acute radiation enteritis. The enhanced biological potency of Mono-PEG-hGLP-2 highlights its potential as a therapeutic agent for intestinal diseases.
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Affiliation(s)
- Tian Zhang
- Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi’an, PR China
| | - Lei Shi
- Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi’an, PR China
| | - Yuan Xu
- Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi’an, PR China
| | - Yang Li
- Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi’an, PR China
| | - Shicao Li
- Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi’an, PR China
| | - Bo Guan
- Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi’an, PR China
| | - Zhihua Qi
- Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi’an, PR China
| | - Ye Zhang
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an, PR China
| | - Linna Liu
- Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi’an, PR China
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Cheng YT, Lin JA, Jhang JJ, Yen GC. Protocatechuic acid-mediated DJ-1/PARK7 activation followed by PI3K/mTOR signaling pathway activation as a novel mechanism for protection against ketoprofen-induced oxidative damage in the gastrointestinal mucosa. Free Radic Biol Med 2019; 130:35-47. [PMID: 30326282 DOI: 10.1016/j.freeradbiomed.2018.10.415] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 09/30/2018] [Accepted: 10/08/2018] [Indexed: 12/31/2022]
Abstract
Oxidative stress contributes to the progression of non-steroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) cell apoptosis. In our previous study, we reported that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a protective role against ketoprofen-induced GI mucosal oxidative injury. Recent reports suggest that Nrf2 could exhibit antioxidative and antiapoptosis responses through up-regulation of DJ-1 (PARK7). In the current study, we proposed that induction of DJ-1 expression by protocatechuic acid (PCA) might provide a potential therapeutic approach for treating oxidative stress-associated GI ulcer diseases. The results indicated that PCA increased mRNA expression of glutathione peroxidase and heme oxygenase-1 through up-regulation of DJ-1 followed by Nrf2 translocation. Furthermore, PCA protected Int-407 cells against ketoprofen-induced oxidative stress by regulating the DJ-1, PI3K, and mTOR pathways. Pretreatment with PCA inhibited mitochondrial ROS generation, up-regulated the mitochondrial membrane potential, and down-regulated pro-apoptotic Bax as well as downstream caspase-8, caspase-9, and caspase-3 activity, and reversed impaired DJ-1 and anti-apoptotic Bcl-2 protein expression in Int-407 cells induced by ketoprofen. Similar to the in vitro results, SD rats treated with PCA before administration of ketoprofen exhibited decreased caspase-3 protein expression as well as oxidative damage, and impairment of the antioxidant system and DJ-1 protein expression in the GI mucosa were reversed. The administration of lansoprazole, a type of proton pump inhibitor (PPI), strongly inhibited ketoprofen-induced GI mucosal injuries via up-regulation of DJ-1, indicating that DJ-1 is essential for the dietary antioxidant- and PPI drug-mediated mechanism of ulcer therapy. These results suggest that DJ-1 could be a novel target for protection against ketoprofen-induced GI ulcers due to its antioxidant and anti-apoptosis characteristics.
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Affiliation(s)
- Yu-Ting Cheng
- Department of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Road, Taichung 40227, Taiwan
| | - Jer-An Lin
- Graduate Institute of Food Safety, National Chung Hsing University, 145 Xingda Road, Taichung 40227, Taiwan
| | - Jhih-Jia Jhang
- Department of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Road, Taichung 40227, Taiwan
| | - Gow-Chin Yen
- Department of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Road, Taichung 40227, Taiwan; Graduate Institute of Food Safety, National Chung Hsing University, 145 Xingda Road, Taichung 40227, Taiwan.
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Selenium in Radiation Oncology-15 Years of Experiences in Germany. Nutrients 2018; 10:nu10040483. [PMID: 29652817 PMCID: PMC5946268 DOI: 10.3390/nu10040483] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 04/05/2018] [Accepted: 04/11/2018] [Indexed: 11/17/2022] Open
Abstract
Introduction: Se measurement and supplementation in radiation oncology is a controversial issue. The German Working Group Trace Elements and Electrolytes in Oncology (AKTE) has conducted a number of studies on this issue, which are summarized in this review. Strategies have been tested and developed, aiming to stratify the patients with a potential need for supplemental Se and how best to monitor Se supplementation with respect to health effects and risks. Methods: We analyzed blood and tissue Se-levels of different tumor patients (n = 512). Two randomized phase III clinical studies were conducted for testing a potential radioprotective effect of supplemental Se during radiation therapy in patients with uterine cancer (n = 81) and head and neck tumor patients (n = 39). Results: A relative Se deficit in whole blood or serum was detected in the majority of tumor patients (carcinomas of the uterus, head and neck, lung, rectal or prostate cancer). In prostate cancer, tissue Se concentrations were relatively elevated in the carcinoma centre as compared to the surrounding compartment or as compared to tumor samples from patients with benign prostatic hyperplasia. Adjuvant Se supplementation successfully corrected Se-deficiency in the patients analyzed and decreased radiotherapy-induced diarrhea in a randomized study of radiotherapy patients with carcinomas of the uterus. Survival data imply that Se supplementation did not interfere with radiation success. Some positive effects of supplemental Se in the prevention of ageusia (loss of taste) and dysphagia due to radiotherapy were noted in a second randomized trial in patients with head and neck cancer. We have not observed any adverse effects of supplemental Se in our studies. Conclusions: Se supplementation yielded promising results concerning radioprotection in tumor patients and should be considered as a promising adjuvant treatment option in subjects with a relative Se deficit.
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Karslioglu Í, Ertekin MV, Koçer Í, Taysi S, Sezen O, Gepdiremen A, Balci E. Protective Role of Intramuscularly Administered Vitamin E on the Levels of Lipid Peroxidation and the Activities of Antioxidant Enzymes in the Lens of Rats Made Cataractous with Gamma-Irradiation. Eur J Ophthalmol 2018. [DOI: 10.1177/112067210401400606] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Í. Karslioglu
- Department of Radiation Oncology, Faculty of Medicine, Atatürk University, Erzurum - Turkey
| | - M. Vecdi Ertekin
- Department of Radiation Oncology, Faculty of Medicine, Atatürk University, Erzurum - Turkey
| | - Í. Koçer
- Department of Ophthalmology, Faculty of Medicine, Atatürk University, Erzurum - Turkey
| | - S. Taysi
- Department of Biochemistry, Faculty of Medicine, Atatürk University, Erzurum - Turkey
| | - O. Sezen
- Department of Radiation Oncology, Faculty of Medicine, Atatürk University, Erzurum - Turkey
| | - A. Gepdiremen
- Department of Pharmacology, Faculty of Medicine, Atatürk University, Erzurum - Turkey
| | - E. Balci
- Department of Radiation Oncology, Faculty of Medicine, Atatürk University, Erzurum - Turkey
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Beytut E, Yilmaz S, Aksakal M, Polat S. The possible protective effects of vitamin E and selenium administration in oxidative stress caused by high doses of glucocorticoid administration in the brain of rats. J Trace Elem Med Biol 2018; 45:131-135. [PMID: 29173469 DOI: 10.1016/j.jtemb.2017.10.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Revised: 06/22/2017] [Accepted: 10/11/2017] [Indexed: 11/17/2022]
Abstract
Acute exposure to high doses of glucocorticoids (GCs) may potentially increase the basal levels of reactive oxygen species (ROS) by altering the defence capacity against oxidative damage. Also, antioxidants may affect the oxidative breakdown of tissues. Therefore, the aim of this work was to determine the effects of dietary intake vitamin E and selenium (Se) on lipid peroxidation (LPO) as thiobarbituric acid reactive substances (TBARS) and on the antioxidative defence mechanisms in the brain of rats treated with high doses of prednisolone. Two hundred and fifty adult male Wistar rats were randomly divided into five groups. The rats were fed a normal diet, but groups 3, 4, and 5 received a daily supplement in their drinking water of 20mg vitamin E, 0.3mg Se, and a combination of vitamin E and Se, respectively, for 30days. For 3days subsequently, the control (group 1) was treated with a placebo, and the remaining 4 groups were injected intramuscularly with 100mg/kg body weight (bw) prednisolone. After the last administration of prednisolone, 10 rats from each group were killed at 4, 8, 12, 24, and 48h and the activities of enzymes selenium-glutathione peroxidase (Se-GSH-Px) and catalase (CAT), and the levels of reduced glutathione (reduced GSH) and TBARS in their brains were measured. Se-GSH-Px and CAT enzyme activities, and reduced GSH levels in the prednisolone treatment group (group 2) began to decrease gradually at 4h (p<0.01, p<0.05, respectively), falling respectively to 60, 50, and 40% of the control levels by 24h (p<0.001, p<0.01), and recovering to the control levels at 48h. In contrast, prednisolone administration caused an increase in the brain TBARS, reaching up to six times the level of the control at 24h (p<0.001). However, supplementation with vitamin E and Se had a preventive effect on the elevation of the brain TBARS and improved the diminished activities of antioxidative enzymes and the levels of reduced GSH. Therefore, the present study attempts to determine the sequence of cellular membrane damage in the brain of the rats after high doses GC administration and the possible roles in vivo of vitamin E and Se, and their combination.
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Affiliation(s)
- Ebru Beytut
- Department of Medical Physiology, Faculty of Medicine, University of Erzincan, Erzincan, TURKEY
| | - Seval Yilmaz
- Department of Biochemistry, Faculty of Veterinary Medicine, University of Firat, Elazıg, TURKEY
| | - Mesut Aksakal
- Department of Physiology, Faculty of Veterinary Medicine, University of Firat, Elazıg, TURKEY
| | - Seher Polat
- Department of Medical Genetics, Faculty of Medicine, University of Erzincan, Erzincan, TURKEY.
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Mishra K, Alsbeih G. Appraisal of biochemical classes of radioprotectors: evidence, current status and guidelines for future development. 3 Biotech 2017; 7:292. [PMID: 28868219 DOI: 10.1007/s13205-017-0925-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 08/21/2017] [Indexed: 12/13/2022] Open
Abstract
The search for efficient radioprotective agents to protect from radiation-induced toxicity, due to planned or accidental radiation exposure, is still ongoing worldwide. Despite decades of research and development of widely different biochemical classes of natural and derivative compounds, a safe and effective radioprotector is largely unmet. In this comprehensive review, we evaluated the evidence for the radioprotective performance of classical thiols, vitamins, minerals, dietary antioxidants, phytochemicals, botanical and bacterial preparations, DNA-binding agents, cytokines, and chelators including adaptogens. Where radioprotection was demonstrated, the compounds have shown moderate dose modifying factors ranging from 1.1 to 2.7. To date, only few compounds found way to clinic with limited margin of dose prescription due to side effects. Most of these compounds (amifostine, filgratism, pegfilgrastim, sargramostim, palifermin, recombinant salmonella flagellin, Prussian blue, potassium iodide) act primarily via scavenging of free radicals, modulation of oxidative stress, signal transduction, cell proliferation or enhance radionuclide elimination. However, the gain in radioprotection remains hampered with low margin of tolerance. Future development of more effective radioprotectors requires an appropriate nontoxic compound, a model system and biomarkers of radiation exposure. These are important to test the effectiveness of radioprotection on physiological tissues during radiotherapy and field application in cases of nuclear eventualities.
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Affiliation(s)
- Krishnanand Mishra
- Radiation Biology Section, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre (KFSH&RC), Riyadh, Saudi Arabia
| | - Ghazi Alsbeih
- Radiation Biology Section, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre (KFSH&RC), Riyadh, Saudi Arabia
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A New Natural Antioxidant Mixture Protects against Oxidative and DNA Damage in Endothelial Cell Exposed to Low-Dose Irradiation. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2017; 2017:9085947. [PMID: 28852434 PMCID: PMC5567450 DOI: 10.1155/2017/9085947] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 05/17/2017] [Accepted: 07/03/2017] [Indexed: 01/13/2023]
Abstract
Exposure to ionizing radiation during diagnostic procedures increases systemic oxidative stress and predisposes to higher risk of cancer and cardiovascular disease development. Many studies indicated that antioxidants protect against radiation-induced damage and have high efficacy and lack of toxicity in preventing radiation exposure damages. The purpose of this study was to investigate the in vitro protective effect of a new antioxidant mixture, named RiduROS, on oxidative stress generation and DNA double-strand breaks (DSBs) induced by low doses of X-rays in endothelial cells. Human umbilical vein endothelial cells (HUVEC) were treated with RiduROS mixture 24 h before a single exposure to X-rays at an absorbed dose of 0.25 Gy. The production of reactive oxygen species (ROS) was evaluated by fluorescent dye staining and nitric oxide (NO) by the Griess reaction, and DSBs were evaluated as number of γ-H2AX foci. We demonstrated that antioxidant mixture reduced oxidative stress induced by low dose of X-ray irradiation and that RiduROS pretreatment is more effective in protecting against radiation-induced oxidative stress than single antioxidants. Moreover, RiduROS mixture is able to reduce γ-H2AX foci formation after low-dose X-ray exposure. The texted mixture of antioxidants significantly reduced oxidative stress and γ-H2AX foci formation in endothelial cells exposed to low-dose irradiation. These results suggest that RiduROS could have a role as an effective radioprotectant against low-dose damaging effects.
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11
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Zhou T, Lu L, Wu S, Zuo L. Effects of Ionizing Irradiation on Mouse Diaphragmatic Skeletal Muscle. Front Physiol 2017; 8:506. [PMID: 28790924 PMCID: PMC5524972 DOI: 10.3389/fphys.2017.00506] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2017] [Accepted: 06/30/2017] [Indexed: 12/22/2022] Open
Abstract
Undesirable exposure of diaphragm to radiation during thoracic radiation therapy has not been fully considered over the past decades. Our study aims to examine the potential biological effects on diaphragm induced by radiation. One-time ionizing irradiation of 10 Gy was applied either to the diaphragmatic region of mice or to the cultured C2C12 myocytes. Each sample was then assayed for muscle function, oxidative stress, or cell viability on days 1, 3, 5, and 7 after irradiation. Our mouse model shows that radiation significantly reduced muscle function on the 5th and 7th days and increased reactive oxygen species (ROS) formation in the diaphragm tissue from days 3 to 7. Similarly, the myocytes exhibited markedly decreased viability and elevated oxidative stress from days 5 to 7 after radiation. These data together suggested that a single dose of 10-Gy radiation is sufficient to cause acute adverse effects on diaphragmatic muscle function, redox balance, and myocyte survival. Furthermore, using the collected data, we developed a physical model to formularize the correlation between diaphragmatic ROS release and time after irradiation, which can be used to predict the biological effects of radiation with a specific dosage. Our findings highlight the importance of developing protective strategies to attenuate oxidative stress and prevent diaphragm injury during radiotherapy.
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Affiliation(s)
- Tingyang Zhou
- Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of MedicineColumbus, OH, United States.,Interdisciplinary Biophysics Graduate Program, The Ohio State UniversityColumbus, OH, United States
| | - Lanchun Lu
- Department of Radiation Oncology, The Ohio State University James Cancer HospitalColumbus, OH, United States
| | - Shiyong Wu
- Edison Biotechnology Institute, Ohio UniversityAthens, OH, United States.,Molecular and Cellular Biology Program, Department of Chemistry and Biochemistry, Ohio UniversityAthens, OH, United States
| | - Li Zuo
- Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of MedicineColumbus, OH, United States.,Interdisciplinary Biophysics Graduate Program, The Ohio State UniversityColumbus, OH, United States
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Neves EG, Ramos-Perez FMDM, Freitas DQ, Bóscolo FN, Almeida SM. Radioprotective effect of sodium selenite on developing teeth. Braz Dent J 2015; 24:375-9. [PMID: 24173260 DOI: 10.1590/0103-6440201302193] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2013] [Accepted: 05/17/2013] [Indexed: 06/22/2024] Open
Abstract
Radioprotective agents like selenium are used to reduce the damage caused by radiation in healthy tissues. The aim of this study was to evaluate the effect of sodium selenite on the development of the molars of offspring of rats irradiated during odontogenesis. Twenty pregnant rats were randomly divided into 4 groups: control, irradiated, selenium and selenium/irradiated. The selenium and selenium/irradiated groups received 0.3 mg/kg of sodium selenite at 18 days of pregnancy. The rats of the irradiated and selenium/irradiated groups received a single dose of 4 Gy of X rays on the abdominal region at the 19th day of pregnancy. The offspring was sacrificed at 3 and 4 days after birth for evaluation of the birefringence of the enamel organic matrix, and at 30 days for evaluation of the intercuspal dimensions of the molars. The selenium/irradiated group was similar to the irradiated group with respect to the thickness and irregularity of the enamel organic matrix region in the evaluated birefringence, as the intercuspal dimensions of the molars. In conclusion, sodium selenite had no radioprotective action on the development of the molars of offspring of rats irradiated during odontogenesis and had a toxic effect in the initial time.
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Affiliation(s)
- Ellen Gaby Neves
- Department of Oral Diagnosis, Oral Radiology Area, Piracicaba School of Dentistry, UNICAMP - University of Campinas, PiracicabaSP, Brazil
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Johnke RM, Sattler JA, Allison RR. Radioprotective agents for radiation therapy: future trends. Future Oncol 2015; 10:2345-57. [PMID: 25525844 DOI: 10.2217/fon.14.175] [Citation(s) in RCA: 109] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Only two radioprotective compounds, amifostine and palifermin, currently have the US FDA approval for use in radiation therapy. However, several agents have been reported that show therapeutic promise. Many of these agents are free radical scavengers/antioxidants. Superoxide dismutase and superoxide dismutase mimetics, nitroxides and dietary antioxidants are all being investigated. Recently, alternative strategies of drug development have been evolving, which focus on targeting the series of cellular insult recognition/repair responses initiated following radiation. These agents, which include cytokines/growth factors, angiotensin-converting enzyme inhibitors and apoptotic modulators, show promise of having significant impact on the mitigation of radiation injury. Herein, we review current literature on the development of radioprotectors with emphasis on compounds with proven or potential usefulness in radiation therapy.
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Affiliation(s)
- Roberta M Johnke
- Department of Radiation Oncology, East Carolina University Brody School of Medicine, Greenville, NC 27834, USA
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Cagin YF, Parlakpinar H, Polat A, Vardi N, Atayan Y, Erdogan MA, Ekici K, Yildiz A, Sarihan ME, Aladag H. The protective effects of apocynin on ionizing radiation-induced intestinal damage in rats. Drug Dev Ind Pharm 2015; 42:317-24. [PMID: 26072994 DOI: 10.3109/03639045.2015.1052080] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND AND AIMS Radiation colitis typically emerges during radiotherapy of intra-abdominal malignancies. While the underlying mechanism remains unclear, it is considered that free oxygen radicals act like cellular mediators to cause colonic damage. Apocynin (APO) prevents oxidative stress and apoptotic cell death by inhibiting NADPH oxidase, and preventing the formation of free oxygen radicals. The aim of the present study was to investigate the protective effect of APO, a strong antioxidant and antiinflammatory agent, on radiation induced colonic oxidative damage in rats. MATERIALS AND METHODS Rats were randomly divided into four groups (n = 8/group). Group I (control group); Group II (Group RAD) received a single dose of 800 cGy ionizing radiation to the whole abdomen with a linear accelerator (LINAC); Group III (Group APO) received a single dose of 20 mg/kg of APO intraperitoneally for five days; Group IV (Group APO+RAD) received APO for five days before radiation exposure (similar to Group III), (similar to Group II). RESULTS APO treatment prior to radiation led to protection in the biochemical and histopathological parameters. CONCLUSIONS Our study shows that APO treatment before radiation improves radiation induced colonic injury in rats, by decreasing oxidative stress and apoptosis.
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Affiliation(s)
| | | | | | - N Vardi
- d Department of Histology and Embryology
| | - Y Atayan
- a Department of Gastroenterology
| | | | - K Ekici
- e Department of Radiation Oncology , and
| | - A Yildiz
- d Department of Histology and Embryology
| | - M E Sarihan
- f Department of Emergency Medicine, Medical Faculty , Inonu University , Malatya , Turkey , and
| | - H Aladag
- g Department of Obstetric & Gynecology , Hayat Hospital , Malatya , Turkey
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15
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Cheng YT, Ho CY, Jhang JJ, Lu CC, Yen GC. DJ-1 plays an important role in caffeic acid-mediated protection of the gastrointestinal mucosa against ketoprofen-induced oxidative damage. J Nutr Biochem 2014; 25:1045-57. [DOI: 10.1016/j.jnutbio.2014.05.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2013] [Revised: 04/30/2014] [Accepted: 05/08/2014] [Indexed: 12/13/2022]
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16
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González-Riaño MG, Repiso R, Delgado López-Cózar E. Repercusión de los rankings universitarios en la prensa española. REVISTA ESPANOLA DE DOCUMENTACION CIENTIFICA 2014. [DOI: 10.3989/redc.2014.3.1128] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
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17
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Camara-Lemarroy CR. Remote ischemic preconditioning as treatment for non-ischemic gastrointestinal disorders: Beyond ischemia-reperfusion injury. World J Gastroenterol 2014; 20:3572-3581. [PMID: 24707140 PMCID: PMC3974524 DOI: 10.3748/wjg.v20.i13.3572] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Revised: 10/23/2013] [Accepted: 01/02/2014] [Indexed: 02/06/2023] Open
Abstract
Common gastrointestinal diseases such as radiation enteritis (RE), acute pancreatitis, inflammatory bowel diseases (IBD) and drug-induced hepatotoxicity share pathophysiological mechanisms at the molecular level, mostly involving the activation of many pathways of the immune response, ultimately leading to tissue injury. Increased oxidative stress, inflammatory cytokine release, inflammatory cell infiltration and activation and the up-regulation of inflammatory transcription factors participate in the pathophysiology of these complex entities. Treatment varies in each specific disease, but at least in the cases of RE and IBD immunosuppressors are effective. However, full therapeutic responses are not always achieved. The pathophysiology of ischemia-reperfusion (IR) injury shares many of these mechanisms. Brief and repetitive periods of ischemia in an organ or limb have been shown to protect against subsequent major IR injury in distant organs, a phenomenon called remote ischemic preconditioning (RIP). This procedure has been shown to protect the gut, pancreas and liver by modulating many of the same inflammatory mechanisms. Since RIP is safe and tolerable, and has shown to be effective in some recent clinical trials, I suggest that RIP could be used as a physiologically relevant adjunct treatment for non-ischemic gastrointestinal inflammatory conditions.
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18
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Does vitamin E protect salivary glands from I-131 radiation damage in patients with thyroid cancer? Nucl Med Commun 2014; 34:777-86. [PMID: 23708871 DOI: 10.1097/mnm.0b013e328362b1f2] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Salivary gland impairment after high-dose radioiodine (¹³¹I) treatment is well recognized. The aim of this study was to determine the protective effect of vitamin E on radiation-induced salivary gland dysfunction in patients undergoing ¹³¹I treatment for differentiated thyroid cancer. METHODS Thirty-six patients with differentiated thyroid carcinoma were enrolled in this study. They were randomly divided into two groups before postsurgical ablation therapy with 3700-5550 MBq ¹³¹I: the control group, comprising 17 patients, and the vitamin E group, comprising 19 patients. All 19 patients in the experimental group received vitamin E at a dose of 800 IU/day for a duration of 1 week before to 4 weeks after I therapy and the 17 patients in the control group received a placebo for the same duration. Salivary gland function was assessed using salivary gland scintigraphy with intravenous injection of 370 MBq Tc-pertechnetate in two phases, one immediately before and the other 6 months after ¹³¹I ablative therapy. First-minute uptake ratio, maximum uptake ratio, maximum secretion percentage, and excretion fraction (EF) of each salivary gland were measured and compared between the study phases for the two groups. RESULTS There was no significant difference between preablative and postablative salivary scintigraphic indices in the experimental vitamin E group, whereas maximum secretion percentage and EF of the right submandibular gland and EF of the left parotid gland were significantly decreased in the control group. There was also a higher significant decrease in the EF of the left parotid gland in the control group compared with the vitamin E group. CONCLUSION Vitamin E consumption may be associated with a significant protective effect against radiation-induced dysfunction in salivary glands following single-dose ¹³¹I therapy in patients with differentiated thyroid cancer.
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19
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Cheng YT, Wu SL, Ho CY, Huang SM, Cheng CL, Yen GC. Beneficial effects of Camellia Oil (Camellia oleifera Abel.) on ketoprofen-induced gastrointestinal mucosal damage through upregulation of HO-1 and VEGF. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2014; 62:642-50. [PMID: 24377395 DOI: 10.1021/jf404614k] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/18/2023]
Abstract
Nonsteroidal anti-inflammatory drugs, such as ketoprofen, are generally used to treat pain and inflammation and as pyretic agents in clinical medicine. However, the usage of these drugs may lead to oxidative injury to the gastrointestinal mucosa. Camellia oil ( Camellia oleifera Abel.) is commonly used in Taiwan and China as cooking oil. Traditional remedies containing this oil exert beneficial health effects on the bowel, stomach, liver, and lungs. However, the effects of camellia oil on ketoprofen-induced oxidative gastrointestinal mucosal lesions remain unknown. The objective of this study was to evaluate the effect of camellia oil on ketoprofen-induced acute gastrointestinal ulcers. The results showed that treatment of Int-407 cells with camellia oil (50-75 μg/mL) not only increased the levels of heme oxygenase-1 (HO-1), glutathione peroxidase (GPx), and superoxide dismutase (SOD) mRNA expression but also increased vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2) protein secretion, which served as a mucosal barrier against gastrointestinal oxidative injury. Moreover, Sprague-Dawley (SD) rats treated with camellia oil (2 mL/kg/day) prior to the administration of ketoprofen (50 mg/kg/day) successfully inhibited COX-2 protein expression, inhibited the production of interleukin-6 (IL-6) and nitrite oxide (NO), reversed the impairment of the antioxidant system, and decreased oxidative damage in the gastrointestinal mucosa. More importantly, pretreatment of SD rats with camellia oil strongly inhibited gastrointestinal mucosal injury induced by ketoprofen, which was proved by the histopathological staining of gastrointestinal tissues. Our data suggest that camellia oil exerts potent antiulcer effects against oxidative damage in the stomach and intestine induced by ketoprofen.
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Affiliation(s)
- Yu-Ting Cheng
- Department of Food Science and Biotechnology, National Chung Hsing University , 250 Kuokuang Road, Taichung 402, Taiwan
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20
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Said RS, Badr AM, Nada AS, El-Demerdash E. Sodium selenite treatment restores long-lasting ovarian damage induced by irradiation in rats: impact on oxidative stress and apoptosis. Reprod Toxicol 2014; 43:85-93. [PMID: 24291358 DOI: 10.1016/j.reprotox.2013.11.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2013] [Revised: 11/12/2013] [Accepted: 11/19/2013] [Indexed: 12/16/2022]
Abstract
The deleterious damage of reproductive function following radiotherapy is of increasing importance. In the present study, we investigated the impact of long-term sodium selenite (SS) treatment on radiotherapy-induced ovarian injury in a rat model. Two-week after radiation exposure vaginal cyclicity was arrested, and serum FSH level was elevated in irradiated female rats. SS significantly ameliorated ovarian and uterine oxidative stress induced by irradiation through decreasing the lipid peroxide level and increasing the glutathione level, and glutathione peroxidase activity. In the presence of SS, ovarian cytochrome c and caspase 3 expressions triggered by radiotherapy were decreased. SS significantly counteracted radiation-induced a widespread loss of ovarian follicles and caused further stimulation of follicular proliferation through enhancing PCNA expression. Despite such alteration in ovarian function, serum estradiol level did not change after irradiation, whereas SS significantly increased it. In conclusion, long-term SS treatment improved reproductive development, which was impaired by radiotherapy.
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Affiliation(s)
- Riham Soliman Said
- National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt
| | - Amira Mohamed Badr
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Ahmed Shafik Nada
- National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt
| | - Ebtehal El-Demerdash
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
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21
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Anzai K, Ueno M, Matsumoto KI, Ikota N, Takata J. Gamma-tocopherol-N,N-dimethylglycine ester as a potent post-irradiation mitigator against whole body X-irradiation-induced bone marrow death in mice. JOURNAL OF RADIATION RESEARCH 2014; 55:67-74. [PMID: 23908555 PMCID: PMC3885127 DOI: 10.1093/jrr/rrt094] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/25/2013] [Revised: 06/05/2013] [Accepted: 06/24/2013] [Indexed: 06/02/2023]
Abstract
We examined the radioprotective and mitigative effects of gamma-tocopherol-N,N-dimethylglycine ester (GTDMG), a novel water-soluble gamma-tocopherol derivative, against X-irradiation-induced bone marrow death in mice. Mice (C3H, 10 weeks, male) were injected intraperitoneally with GTDMG suspended in a 0.5% methyl cellulose solution before or after receiving of 7.5-Gy whole body X-irradiation. GTDMG significantly enhanced the 30-day survival rate when given 30 min before or immediately after the irradiation. Its mitigative activity (administered after exposure) was examined further in detail. The optimal concentration of GTDMG given immediately after irradiation was around 100 mg/kg body weight (bw) and the 30-day survival rate was 97.6 ± 2.4%. When GTDMG was administered 1, 10 and 24 h post-irradiation, the survival rate was 85.7 ± 7.6, 75.0 ± 9.7 and 36.7 ± 8.8%, respectively, showing significant mitigation even at 24 h after irradiation (P < 0.05). The value of the dose reduction factor (100 mg/kg bw, given intraperitoneally (i.p.) immediately after irradiation) was 1.25. GTDMG enhanced the recovery of red blood cell-, white blood cell-, and platelet-counts after irradiation and significantly increased the number of endogenous spleen colonies (P < 0.05). Subcutaneous (s.c.) administration also had mitigative effects. In conclusion, GTDMG is a potent radiation mitigator.
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Affiliation(s)
- Kazunori Anzai
- Nihon Pharmaceutical University
- National Institute of Radiological Sciences
| | | | | | | | - Jiro Takata
- Faculty of Pharmaceutical Sciences, Fukuoka University
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22
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Stacey R, Green JT. Radiation-induced small bowel disease: latest developments and clinical guidance. Ther Adv Chronic Dis 2014; 5:15-29. [PMID: 24381725 PMCID: PMC3871275 DOI: 10.1177/2040622313510730] [Citation(s) in RCA: 133] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Ionizing radiation is commonly used to treat a number of malignancies. Although highly effective and now more targeted, many patients suffer side effects. The number of cancer survivors has increased and so there are more patients presenting with symptoms that have arisen as a result of radiotherapy. Radiation damage to small bowel tissue can cause acute or chronic radiation enteritis producing symptoms such as pain, bloating, nausea, faecal urgency, diarrhoea and rectal bleeding which can have a significant impact on patient's quality of life. This review outlines the pathogenesis of radiation injury to the small bowel along with the prevention of radiation damage via radiotherapy techniques plus medications such as angiotensin-converting enzyme inhibitors, statins and probiotics. It also covers the treatment of both acute and chronic radiation enteritis via a variety of medical (including hyperbaric oxygen), dietetic, endoscopic and surgical therapies.
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Affiliation(s)
- Rhodri Stacey
- Gastroenterology Registrar, University Hospital Llandough, Cardiff and Vale University Health Board, South Wales, UK
| | - John T Green
- Consultant Gastroenterologist, Department of Gastroenterology, University Hospital Llandough, Penlan Road, Penarth CF64 2XX, UK
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23
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Giardi MT, Touloupakis E, Bertolotto D, Mascetti G. Preventive or potential therapeutic value of nutraceuticals against ionizing radiation-induced oxidative stress in exposed subjects and frequent fliers. Int J Mol Sci 2013; 14:17168-92. [PMID: 23965979 PMCID: PMC3759958 DOI: 10.3390/ijms140817168] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Revised: 08/01/2013] [Accepted: 08/12/2013] [Indexed: 12/19/2022] Open
Abstract
Humans are constantly exposed to ionizing radiation deriving from outer space sources or activities related to medical care. Absorption of ionizing radiation doses over a prolonged period of time can result in oxidative damage and cellular dysfunction inducing several diseases, especially in ageing subjects. In this report, we analyze the effects of ionizing radiation, particularly at low doses, in relation to a variety of human pathologies, including cancer, and cardiovascular and retinal diseases. We discuss scientific data in support of protection strategies by safe antioxidant formulations that can provide preventive or potential therapeutic value in response to long-term diseases that may develop following exposure.
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Affiliation(s)
| | - Eleftherios Touloupakis
- Biosensor, Via Olmetti 44 Formello, Rome 00060, Italy; E-Mail:
- Department of Chemistry, University of Crete, P.O. Box 2208, Voutes-Heraklion 71003, Greece
| | - Delfina Bertolotto
- Agenzia Spaziale Italiana (ASI), Viale Liegi 26, Rome 00198, Italy; E-Mails: (D.B.); (G.M.)
| | - Gabriele Mascetti
- Agenzia Spaziale Italiana (ASI), Viale Liegi 26, Rome 00198, Italy; E-Mails: (D.B.); (G.M.)
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24
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Cheng YT, Wu CH, Ho CY, Yen GC. Catechin protects against ketoprofen-induced oxidative damage of the gastric mucosa by up-regulating Nrf2 in vitro and in vivo. J Nutr Biochem 2013; 24:475-83. [DOI: 10.1016/j.jnutbio.2012.01.010] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2011] [Revised: 01/14/2012] [Accepted: 01/19/2012] [Indexed: 12/22/2022]
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Said RS, Nada AS, El-Demerdash E. Sodium selenite improves folliculogenesis in radiation-induced ovarian failure: a mechanistic approach. PLoS One 2012; 7:e50928. [PMID: 23236409 PMCID: PMC3516513 DOI: 10.1371/journal.pone.0050928] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2012] [Accepted: 10/25/2012] [Indexed: 01/14/2023] Open
Abstract
Radiotherapy is a major factor contributing to female infertility by inducing premature ovarian failure (POF). Therefore, the need for an effective radioprotective agent is evident. The present study investigated the mechanism of potential radioprotective effect of sodium selenite on radiation-induced ovarian failure and whether sodium selenite can stimulate in-vivo follicular development in experimental rats. Immature female Sprague-Dawely rats were either exposed to gamma-radiation (3.2 Gy, LD(20)), once and/or treated with sodium selenite (0.5 mg/kg), once daily for one week before irradiation. Follicular and oocyte development, apoptotic markers, proliferation marker as well as oxidative stress markers were assessed 24-h after irradiation. In addition, fertility assessment was performed after female rats became completely mature at two months of age. Sodium selenite significantly enhanced follicular development as compared to the irradiated group. Sodium selenite significantly reversed the oxidative stress effects of radiation that was evidenced by increasing in lipid peroxide level and decreasing in glutathione level, and glutathione peroxidase (GPx) activity. Assessment of apoptosis and cell proliferation markers revealed that caspase 3 and cytochrome c expressions markedly-increased, whereas, PCNA expression markedly-decreased in the irradiated group; in contrast, sodium selenite treatment prevented these alterations. Histopathological examination further confirmed the radioprotective efficacy of sodium selenite and its in-vivo effect on ovarian follicles' maturation. In conclusion, sodium selenite showed a radioprotective effect and improved folliculogenesis through increasing ovarian granulosa cells proliferation, estradiol and FSH secretion, and GPx activity, whilst decreasing lipid peroxidation and oxidative stress, leading to inhibition of the apoptosis pathway through decreasing the expressions of caspase 3 and cytochrome c.
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Affiliation(s)
- Riham S. Said
- National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt
| | - Ahmed S. Nada
- National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt
| | - Ebtehal El-Demerdash
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
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26
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Couto MR, Gonçalves P, Catarino T, Araújo JR, Correia-Branco A, Martel F. The effect of oxidative stress upon the intestinal uptake of folic acid: in vitro studies with Caco-2 cells. Cell Biol Toxicol 2012; 28:369-81. [PMID: 22956110 DOI: 10.1007/s10565-012-9228-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2012] [Accepted: 07/18/2012] [Indexed: 10/27/2022]
Abstract
Folic acid (FA) is a vitamin essential for normal cellular functions, growth, and development. Because humans cannot synthesize this micronutrient, it must be obtained from dietary sources through intestinal absorption. The intestinal tract is a major target for oxidative stress. Our aim was to investigate the effect of oxidative stress upon the uptake of FA by Caco-2 cells. Oxidative stress was induced by exposure of the cells to tert-butyl hydroperoxide (TBH) for 1 h. TBH (3,000 μM) induced an increase in biomarkers of oxidative stress, while maintaining cell viability and proliferation. In relation to the apical uptake of (3)H-FA, TBH (3,000 μM) reduced the cellular accumulation of (3)H-FA (10 nM), although the characteristics (kinetics, pH dependence, and inhibitory profile) of (3)H-FA uptake were not changed. This effect was associated with a decrease in the mRNA steady-state levels of proton-coupled folate transporter and folate receptor alpha and of the efflux transporter multidrug resistance protein 2. Moreover, TBH (3,000 μM) did not affect the noncarrier-mediated apical uptake of (3)H-FA. Finally, the effect of TBH upon (3)H-FA apical uptake was not dependent on protein kinase A, protein kinase C, mitogen-activated protein kinases, phosphoinositide 3-kinase, nuclear factor kappa B, and protein tyrosine kinases, but was completely prevented by dietary polyphenols (resveratrol, quercetin, and EGCG). These results suggest that oxidative stress at the intestinal level may result in a reduction in the intestinal absorption of dietary FA and that polyphenolic dietary components may offer protection against oxidative stress-induced inhibition of intestinal FA absorption.
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Affiliation(s)
- Mafalda R Couto
- Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal
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27
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Shirazi A, Mihandoost E, Mahdavi SR, Mohseni M. Radio-protective role of antioxidant agents. Oncol Rev 2012; 6:e16. [PMID: 25992214 PMCID: PMC4419622 DOI: 10.4081/oncol.2012.e16] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2012] [Revised: 03/22/2012] [Accepted: 07/05/2012] [Indexed: 12/03/2022] Open
Abstract
Ionizing radiation interacts with biological systems to produce reactive oxygen species and reactive nitrogen species which attack various cellular components. Radio-protectors act as prophylactic agents to shield healthy cells and tissues from the harmful effects of radiation. Past research on synthetic radio-protectors has brought little success, primarily due to the various toxicity-related problems. Results of experimental research show that antioxidant nutrients, such as vitamin E and herbal products and melatonin, are protective against the damaging effects of radiation, with less toxicity and side effects. Therefore, we propose that in the future, antioxidant radio-protective agents may improve the therapeutic index in radiation oncology treatments.
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Affiliation(s)
- Alireza Shirazi
- Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran
| | - Ehsan Mihandoost
- Department of Medical Radiation Engineering, Science and Research Branch, Islamic Azad University, Tehran
| | - Seied Rabie Mahdavi
- Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran
| | - Mehran Mohseni
- Department of Radiology and Medical Physics, Faculty of Paramedicine, Kashan University of Medical Sciences, Kashan, Iran
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28
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Pophaly SD, Singh R, Pophaly SD, Kaushik JK, Tomar SK. Current status and emerging role of glutathione in food grade lactic acid bacteria. Microb Cell Fact 2012; 11:114. [PMID: 22920585 PMCID: PMC3462692 DOI: 10.1186/1475-2859-11-114] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2012] [Accepted: 08/18/2012] [Indexed: 12/15/2022] Open
Abstract
Lactic acid bacteria (LAB) have taken centre stage in perspectives of modern fermented food industry and probiotic based therapeutics. These bacteria encounter various stress conditions during industrial processing or in the gastrointestinal environment. Such conditions are overcome by complex molecular assemblies capable of synthesizing and/or metabolizing molecules that play a specific role in stress adaptation. Thiols are important class of molecules which contribute towards stress management in cell. Glutathione, a low molecular weight thiol antioxidant distributed widely in eukaryotes and Gram negative organisms, is present sporadically in Gram positive bacteria. However, new insights on its occurrence and role in the latter group are coming to light. Some LAB and closely related Gram positive organisms are proposed to possess glutathione synthesis and/or utilization machinery. Also, supplementation of glutathione in food grade LAB is gaining attention for its role in stress protection and as a nutrient and sulfur source. Owing to the immense benefits of glutathione, its release by probiotic bacteria could also find important applications in health improvement. This review presents our current understanding about the status of glutathione and its role as an exogenously added molecule in food grade LAB and closely related organisms.
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Affiliation(s)
- Sarang Dilip Pophaly
- Dairy Microbiology Division, National Dairy Research Institute, Karnal, Haryana, India, 132001
| | - Rameshwar Singh
- Dairy Microbiology Division, National Dairy Research Institute, Karnal, Haryana, India, 132001
| | | | - Jai K Kaushik
- Animal Biotechnology Centre, National Dairy Research Institute, Karnal, Haryana, India, 132001
| | - Sudhir Kumar Tomar
- Dairy Microbiology Division, National Dairy Research Institute, Karnal, Haryana, India, 132001
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Christophersen OA. Radiation protection following nuclear power accidents: a survey of putative mechanisms involved in the radioprotective actions of taurine during and after radiation exposure. MICROBIAL ECOLOGY IN HEALTH AND DISEASE 2012; 23:14787. [PMID: 23990836 PMCID: PMC3747764 DOI: 10.3402/mehd.v23i0.14787] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/18/2011] [Accepted: 11/18/2011] [Indexed: 12/28/2022]
Abstract
There are several animal experiments showing that high doses of ionizing radiation lead to strongly enhanced leakage of taurine from damaged cells into the extracellular fluid, followed by enhanced urinary excretion. This radiation-induced taurine depletion can itself have various harmful effects (as will also be the case when taurine depletion is due to other causes, such as alcohol abuse or cancer therapy with cytotoxic drugs), but taurine supplementation has been shown to have radioprotective effects apparently going beyond what might be expected just as a consequence of correcting the harmful consequences of taurine deficiency per se. The mechanisms accounting for the radioprotective effects of taurine are, however, very incompletely understood. In this article an attempt is made to survey various mechanisms that potentially might be involved as parts of the explanation for the overall beneficial effect of high levels of taurine that has been found in experiments with animals or isolated cells exposed to high doses of ionizing radiation. It is proposed that taurine may have radioprotective effects by a combination of several mechanisms: (1) during the exposure to ionizing radiation by functioning as an antioxidant, but perhaps more because it counteracts the prooxidant catalytic effect of iron rather than functioning as an important scavenger of harmful molecules itself, (2) after the ionizing radiation exposure by helping to reduce the intensity of the post-traumatic inflammatory response, and thus reducing the extent of tissue damage that develops because of severe inflammation rather than as a direct effect of the ionizing radiation per se, (3) by functioning as a growth factor helping to enhance the growth rate of leukocytes and leukocyte progenitor cells and perhaps also of other rapidly proliferating cell types, such as enterocyte progenitor cells, which may be important for immunological recovery and perhaps also for rapid repair of various damaged tissues, especially in the intestines, and (4) by functioning as an antifibrogenic agent. A detailed discussion is given of possible mechanisms involved both in the antioxidant effects of taurine, in its anti-inflammatory effects and in its role as a growth factor for leukocytes and nerve cells, which might be closely related to its role as an osmolyte important for cellular volume regulation because of the close connection between cell volume regulation and the regulation of protein synthesis as well as cellular protein degradation. While taurine supplementation alone would be expected to exert a therapeutic effect far better than negligible in patients that have been exposed to high doses of ionizing radiation, it may on theoretical grounds be expected that much better results may be obtained by using taurine as part of a multifactorial treatment strategy, where it may interact synergistically with several other nutrients, hormones or other drugs for optimizing antioxidant protection and minimizing harmful posttraumatic inflammatory reactions, while using other nutrients to optimize DNA and tissue repair processes, and using a combination of good diet, immunostimulatory hormones and perhaps other nontoxic immunostimulants (such as beta-glucans) for optimizing the recovery of antiviral and antibacterial immune functions. Similar multifactorial treatment strategies may presumably be helpful in several other disease situations (including severe infectious diseases and severe asthma) as well as for treatment of acute intoxications or acute injuries (both mechanical ones and severe burns) where severely enhanced oxidative and/or nitrative stress and/or too much secretion of vasodilatory neuropeptides from C-fibres are important parts of the pathogenetic mechanisms that may lead to the death of the patient. Some case histories (with discussion of some of those mechanisms that may have been responsible for the observed therapeutic outcome) are given for illustration of the likely validity of these concepts and their relevance both for treatment of severe infections and non-infectious inflammatory diseases such as asthma and rheumatoid arthritis.
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Freitas DQD, Ramos-Perez FMDM, Neves EG, Marques MR, Bóscolo FN, Almeida SMD. Radioprotective effect of sodium selenite on bone repair in the tibia of ovariectomized rats. Braz Dent J 2012; 23:723-8. [DOI: 10.1590/s0103-64402012000600017] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Accepted: 11/05/2012] [Indexed: 11/22/2022] Open
Abstract
This studyevaluated protection by selenium (Se) in the bone repair process in ovariectomized rats after irradiation. For such purpose, 80 ovariectomized female Wistar rats were randomly divided into 4 experimental groups: ovariectomized (Ov), Ov/Se, Ov/irradiated (Irr) and Ov/ Se/Irr. A bone defect was created on the tibia of all animals 40 days after ovariectomy. Two days after surgery, only the Ov/Se and Ov/Se/Irr rats received 0.8 mg Se/kg. Three days after surgery, only the Ov/Irr and Ov/Se/Irr rats received 10 Gy of x-rays on the lower limb region. The animals were euthanized at 7, 14, 21 and 28 days after surgery to assess the repair process, which was evaluated by analysis of trabecular bone number (Masson Trichrome) and birefringence analysis (Picrosirius). It was possible to observe a delay in the bone repair process in the ovariectomized/irradiated group and similarity between the ovariectomized, Ov/Se and Ov/Se/Irr groups. In conclusion, sodium selenite exerted a radioprotective effect in the bone repair of tibia of ovariectomized rats without toxicity.
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Longobardi B, Berardi G, Fiorino C, Alongi F, Cozzarini C, Deli A, Macchia ML, Perna L, Di Muzio NG, Calandrino R. Anatomical and clinical predictors of acute bowel toxicity in whole pelvis irradiation for prostate cancer with Tomotherapy. Radiother Oncol 2011; 101:460-4. [DOI: 10.1016/j.radonc.2011.07.014] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2010] [Revised: 07/11/2011] [Accepted: 07/12/2011] [Indexed: 11/16/2022]
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Spyropoulos BG, Misiakos EP, Fotiadis C, Stoidis CN. Antioxidant properties of probiotics and their protective effects in the pathogenesis of radiation-induced enteritis and colitis. Dig Dis Sci 2011; 56:285-94. [PMID: 20632107 DOI: 10.1007/s10620-010-1307-1] [Citation(s) in RCA: 81] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2010] [Accepted: 06/14/2010] [Indexed: 12/20/2022]
Abstract
Radiation therapy has become one of the most important treatment modalities for human malignancy, but certain immediate and delayed side-effects on the normal surrounding tissues limit the amount of effective radiation that can be administered. After exposure of the abdominal region to ionizing radiation, nearly all patients experience transient symptoms of irradiation of the bowel. Acute-phase symptoms may persist for a short time, yet long-term complications can represent significant clinical conditions with high morbidity. Data from both experimental studies and clinical trials suggest the potential benefit for probiotics in radiation-induced enteritis and colitis. On the other hand, it is well evidenced that both useful and harmful effects of therapeutic applications of ionizing radiation upon living systems are ascribed to free-radical production. Therefore, the hypothesis that probiotics reinforce antioxidant defense systems of normal mucosal cells exposed to ionizing radiation may explain to an extent their beneficial action. The aim of this review is threefold: First, to make a short brief into the natural history of radiation injury to the intestinal tract. Second, to describe the primary interaction of ionizing radiation at the cellular level and demonstrate the participation of free radicals in the mechanisms of injury and, third, to try a more profound investigation into the antioxidant abilities of probiotics and prebiotics based on the available experimental and clinical data.
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Affiliation(s)
- Basileios G Spyropoulos
- 1st Department of Propaedeutic Surgery, University of Athens School of Medicine, Hippokration Hospital, Athens, Greece.
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Crescenti EJV, Medina VA, Croci M, Sambuco LA, Prestifilippo JP, Elverdin JC, Bergoc RM, Rivera ES. Radioprotection of sensitive rat tissues by oligoelements Se, Zn, Mn plus Lachesis muta venom. JOURNAL OF RADIATION RESEARCH 2011; 52:557-567. [PMID: 21952314 DOI: 10.1269/jrr.11031] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
In this study we first evaluated the general radioprotective efficacy of Se, Zn and Mn (4 µg/ml each) plus Lachesis muta venom (4 ng/ml) combination (O-LM) by determining survival on rats irradiated with lethal doses of gamma-rays. The aim of the second part of the study was to investigate the O-LM ability to prevent ionizing radiation-induced damage on small intestine, bone marrow and submandibular glands. Hence, histological characteristics and functional studies, together with proliferation and apoptotic marker levels on whole body irradiated rats with a 5 Gy dose were evaluated. Results show that all animals of the untreated group died after whole body irradiation with 8 and 10 Gy while 60 day-survival was more than 80% and 40% in O-LM-treated animals, respectively. Histopathological examinations revealed a high degree of small intestine and submandibular gland radioprotection 3 days post-irradiation. O-LM inhibited histological damage on small intestine, restoring the radiation-induced reduction in villous height and crypt number. O-LM prevented radiation-induced loss of salivary gland function and morphological alterations. These effects were associated to a complete inhibition of radiation-induced apoptosis. Furthermore, studies performed 30 days post-irradiation revealed that O-LM significantly improved bone marrow repopulation, increasing all medullar progenies to the extent of the non-irradiated animals, and completely prevented permanent submandibular gland alterations. Based on the present results and taking into account that O-LM is being safely administered in phase I clinical trial as an immunomodulator, we conclude that O-LM is a non-toxic promising approach to achieve radioprotection for patients undergoing radiotherapy.
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Roche M, Kemp FW, Agrawal A, Attanasio A, Neti PVSV, Howell RW, Ferraris RP. Marked changes in endogenous antioxidant expression precede vitamin A-, C-, and E-protectable, radiation-induced reductions in small intestinal nutrient transport. Free Radic Biol Med 2011; 50:55-65. [PMID: 20970494 PMCID: PMC3014460 DOI: 10.1016/j.freeradbiomed.2010.10.689] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2010] [Revised: 09/20/2010] [Accepted: 10/11/2010] [Indexed: 11/18/2022]
Abstract
Rapidly proliferating epithelial crypt cells of the small intestine are susceptible to radiation-induced oxidative stress, yet there is a dearth of data linking this stress to expression of antioxidant enzymes and to alterations in intestinal nutrient absorption. We previously showed that 5-14 days after acute γ-irradiation, intestinal sugar absorption decreased without change in antioxidant enzyme expression. In the present study, we measured antioxidant mRNA and protein expression in mouse intestines taken at early times postirradiation. Observed changes in antioxidant expression are characterized by a rapid decrease within 1h postirradiation, followed by dramatic upregulation within 4h and then downregulation a few days later. The cell type and location expressing the greatest changes in levels of the oxidative stress marker 4HNE and of antioxidant enzymes are, respectively, epithelial cells responsible for nutrient absorption and the crypt region comprising mainly undifferentiated cells. Consumption of a cocktail of antioxidant vitamins A, C, and E, before irradiation, prevents reductions in transport of intestinal sugars, amino acids, bile acids, and peptides. Ingestion of antioxidants may blunt radiation-induced decreases in nutrient transport, perhaps by reducing acute oxidative stress in crypt cells, thereby allowing the small intestine to retain its absorptive function when those cells migrate to the villus days after the insult.
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Affiliation(s)
- Marjolaine Roche
- Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine & Dentistry of New Jersey, Newark, NJ, USA
| | - Francis W Kemp
- Department of Preventive Medicine & Community Health, New Jersey Medical School, University of Medicine & Dentistry of New Jersey, Newark, NJ, USA
| | - Amit Agrawal
- Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine & Dentistry of New Jersey, Newark, NJ, USA
| | - Alicia Attanasio
- Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine & Dentistry of New Jersey, Newark, NJ, USA
| | - Prasad VSV Neti
- Department of Radiology, New Jersey Medical School Cancer Center, University of Medicine & Dentistry of New Jersey, Newark, NJ, USA
| | - Roger W Howell
- Department of Radiology, New Jersey Medical School Cancer Center, University of Medicine & Dentistry of New Jersey, Newark, NJ, USA
| | - Ronaldo P Ferraris
- Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine & Dentistry of New Jersey, Newark, NJ, USA
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Olsson MG, Nilsson EJC, Rutardóttir S, Paczesny J, Pallon J, Åkerström B. Bystander Cell Death and Stress Response is Inhibited by the Radical Scavenger α1-Microglobulin in Irradiated Cell Cultures. Radiat Res 2010; 174:590-600. [DOI: 10.1667/rr2213.1] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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Hepgül G, Tanrikulu S, Unalp HR, Akguner T, Erbil Y, Olgaç V, Ademoğlu E. Preventive effect of pentoxifylline on acute radiation damage via antioxidant and anti-inflammatory pathways. Dig Dis Sci 2010; 55:617-25. [PMID: 19294507 DOI: 10.1007/s10620-009-0780-x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2008] [Accepted: 02/23/2009] [Indexed: 12/19/2022]
Abstract
PURPOSE The aim of the present study was to investigate whether pentoxifylline (PTX) treatment could protect against induced acute radiation enteritis. METHOD Rats received 100 mg/kg/day PTX for 7 days before irradiation and continued on treatment for 3 days after irradiation. The intestinal myeloperoxidase (MPO) activities and malondialdehyde (MDA), glutathione (GSH), prostaglandin E2, and thromboxane B2 levels were determined. Terminal ileum tissue was evaluated for morphological changes. Also, nuclear factor kappa (NF-kappa), tumor necrosis factor-alpha (TNF-alpha), and intercellular adhesion molecule 1 (ICAM-1) expressions were analyzed with immunohistochemisty methods. RESULTS PTX treatment was associated with increased GSH levels and decreased MPO activity and MDA, prostaglandin E2, and thromboxane B2 levels. Histopathologic examination showed that intestinal mucosal structure was preserved in the PTX-treated group while having significant decreases in NF-kappaB, TNF-a, and ICAM-1 expression. CONCLUSIONS PTX appears to have a protective effect against radiation damage. This protective effect is mediated in part by decreasing both inflammatory reactions and oxidative stress.
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Affiliation(s)
- Gülçin Hepgül
- Istanbul Medical Faculty, Department of General Surgery, Istanbul University, Istanbul, Turkey
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Pontual MLDA, Tuji FM, Barros SP, Bóscolo FN, Novaes PD, de Almeida SM. Ultrastructural evaluation of the radioprotective effect of sodium selenite on submandibular glands in rats. J Appl Oral Sci 2009; 15:162-8. [PMID: 19089124 PMCID: PMC4327461 DOI: 10.1590/s1678-77572007000300003] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2005] [Accepted: 03/22/2007] [Indexed: 11/22/2022] Open
Abstract
The aim of this study was to evaluate the radioprotector effect of sodium selenite on the ultrastructure of submandibular glands in rats. Fifty-seven male albino Wistar rats were randomized to 4 groups: control, irradiated, sodium selenite and irradiated/sodium selenite. The animals in the sodium selenite and irradiated/sodium selenite groups received intraperitoneal injections of sodium selenite (0.5 mg/kg body weight) 24 h before irradiation. The animals belonging to the irradiated and irradiated/sodium selenite groups were submitted to 15 Gy of gamma radiation in the head and neck region. The submandibular glands were removed at 4, 8, 12, 24, 48 and 72 h after irradiation. The ionizing radiation induced damage to the secretory cells, especially the serous cells, right from the first period. Vacuolization, lysis of cytoplasmic inclusions and nuclear alterations occurred. The sodium selenite group also presented cellular alterations in the study periods, but with less damage compared to that caused by radiation. There was greater similarity between the irradiated/sodium selenite group and the control group than with the other groups treated in all study periods. Despite the alterations observed in the sodium selenite group, sodium selenite presented a radioprotective action on the secretory cells of submandibular glands.
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Affiliation(s)
- Maria Luiza dos Anjos Pontual
- Department of Clinic and Social Dentistry, School of Dentistry, Federal University of Paraíba, João Pessoa, PB, Brazil.
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Micke O, Schomburg L, Buentzel J, Kisters K, Muecke R. Selenium in oncology: from chemistry to clinics. Molecules 2009; 14:3975-88. [PMID: 19924043 PMCID: PMC6255034 DOI: 10.3390/molecules14103975] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2009] [Revised: 09/26/2009] [Accepted: 09/30/2009] [Indexed: 12/02/2022] Open
Abstract
The essential trace element selenium, which is a crucial cofactor in the most important endogenous antioxidative systems of the human body, is attracting more and more the attention of both laypersons and expert groups. The interest of oncologists mainly focuses in the following clinical aspects: radioprotection of normal tissues, radiosensitizing in malignant tumors, antiedematous effect, prognostic impact of selenium, and effects in primary and secondary cancer prevention. Selenium is a constituent of the small group of selenocysteine-containing selenoproteins and elicits important structural and enzymatic functions. Selenium deficiency has been linked to increased infection risk and adverse mood states. It has been shown to possess cancer-preventive and cytoprotective activities in both animal models and humans. It is well established that Se has a key role in redox regulation and antioxidant function, and hence in membrane integrity, energy metabolism and protection against DNA damage. Recent clinical trials have shown the importance of selenium in clinical oncology. Our own clinical study involving 48 patients suggest that selenium has a positive effect on radiation-associated secondary lymphedema in patients with limb edemas, as well as in the head and neck region, including endolaryngeal edema. Another randomized phase III study of our group was performed to examine the cytoprotective properties of selenium in radiation oncology. The aim was to evaluate whether sodium selenite is able to compensate a preexisting selenium deficiency and to prevent radiation induced diarrhea in adjuvant radiotherapy for pelvic gynecologic malignancies. Through this study, the significant benefits of sodium selenite supplementation with regards to selenium deficiency and radiotherapy induced diarrhea in patients with cervical and uterine cancer has been shown for the first time in a prospective randomized trial. Survival data imply that supplementation with selenium does not interfere with the positive biological effects of radiation treatment and might constitute a valuable adjuvant therapy option especially in marginally supplied individuals. More recently there were emerging concerns coming up from two large clinical prevention trials (NPC, SELECT), that selenium increases the possible risk of developing diabetes type II. Despite obvious flaws of both studies and good counterarguments, a controversial debate remains on the possible advantage and risks of selenium in cancer prevention. However, in the light of the recent clinical trials the potential benefits of selenium supplementation in tumor patients are undeniable, even if further research is needed.
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Affiliation(s)
- Oliver Micke
- Department of Radiotherapy and Radiation Oncology, Franziskus Hospital, Kiskerstraße 26, D-33615 Bielefeld, Germany
| | - Lutz Schomburg
- Institute for Experimental Endocrinology, Charité Berlin, Germany; E-Mail: (L.S.)
| | - Jens Buentzel
- Department of Otolaryngology, Südharz Hospital Nordhausen, Germany; E-Mail: (J.B.)
| | - Klaus Kisters
- Department of Internal Medicine, St. Anna Hospital, Herne, Germany; E-Mail: (K.K.)
| | - Ralph Muecke
- Department of Radiotherapy, Lippe Hospital Lemgo, Germany; E-Mail: (R.M.)
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Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy. Med Oncol 2009; 27:919-25. [PMID: 19757213 DOI: 10.1007/s12032-009-9307-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2009] [Accepted: 09/03/2009] [Indexed: 02/01/2023]
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Effect of water soluble vitamins on Zn transport of Caco-2 cells and their implications under oxidative stress conditions. Eur J Nutr 2009; 49:53-61. [DOI: 10.1007/s00394-009-0048-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2009] [Accepted: 07/30/2009] [Indexed: 11/27/2022]
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Abstract
Radiation colitis, an insidious, progressive disease of increasing frequency, develops 6 mo to 5 years after regional radiotherapy for malignancy, owing to the deleterious effects of the latter on the colon and the small intestine. When dealing with radiation colitis and its complications, the most conservative modality should be employed because the areas of intestinal injury do not tend to heal. Acute radiation colitis is mostly self-limited, and usually, only supportive management is required. Chronic radiation colitis, a poorly predictable progressive disease, is considered as a precancerous lesion; radiation-associated malignancy has a tendency to be diagnosed at an advanced stage and to bear a dismal prognosis. Therefore, management of chronic radiation colitis remains a major challenge owing to the progressive evolution of the disease, including development of fibrosis, endarteritis, edema, fragility, perforation, partial obstruction, and cancer. Patients are commonly managed conservatively. Surgical intervention is difficult to perform because of the extension of fibrosis and alterations in the gut and mesentery, and should be reserved for intestinal obstruction, perforation, fistulas, and severe bleeding. Owing to the difficulty in managing the complications of acute and chronic radiation colitis, particular attention should be focused onto the prevention strategies. Uncovering the fibrosis mechanisms and the molecular events underlying radiation bowel disease could lead to the introduction of new therapeutic and/or preventive approaches. A variety of novel, mostly experimental, agents have been used mainly as a prophylaxis, and improvements have been made in radiotherapy delivery, including techniques to reduce the amount of exposed intestine in the radiation field, as a critical strategy for prevention.
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Sezen O, Ertekin MV, Demircan B, Karslıoğlu İ, Erdoğan F, Koçer İ, Çalık İ, Gepdiremen A. Vitamin E and l-carnitine, separately or in combination, in the prevention of radiation-induced brain and retinal damages. Neurosurg Rev 2008; 31:205-13; discussion 213. [DOI: 10.1007/s10143-007-0118-0] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2007] [Revised: 06/28/2007] [Accepted: 11/11/2007] [Indexed: 10/22/2022]
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Assimakopoulos SF, Maroulis I, Patsoukis N, Vagenas K, Scopa CD, Georgiou CD, Vagianos CE. Effect of antioxidant treatments on the gut-liver axis oxidative status and function in bile duct-ligated rats. World J Surg 2007; 31:2023-32. [PMID: 17665241 DOI: 10.1007/s00268-007-9191-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Experimental and clinical studies have demonstrated the pivotal role of oxidative stress in the promotion of hepatic and intestinal injury in obstructive jaundice. The present study was undertaken to investigate the effect of well known antioxidant treatments on the gut-liver axis oxidative status and function in bile duct-ligated rats. METHODS A total of 60 male Wistar rats were randomly divided into six groups of 10 animals each: controls, sham operated, bile duct ligated (BDL), and BDL treated with either N-acetylcysteine (NAC), allopurinol, or alpha-tocopherol (alpha-TC). Ten days after treatment, the hepatic and intestinal oxidative status was estimated by measuring lipid peroxidation and a battery of biochemical markers comprising the organ's thiol redox state (i.e., glutathione, cysteine, protein thiols, oxidized glutathione, nonprotein mixed disulfides, oxidized cysteine derivatives, protein symmetrical disulfides, and protein mixed disulfides). Portal and aortic endotoxin concentrations and alanine aminotransferase (ALT) levels were also determined. RESULTS All antioxidant treatments significantly improved intestinal barrier function and protected from cholestatic liver injury, as evidenced by reduction of the portal and aortic endotoxin concentration and ALT levels, respectively. This effect accompanied their significant antioxidant action in both organs, mediated by a certain influence profile on the thiol redox state by each treatment. CONCLUSION NAC, allopurinol, and alpha-TC, exerting a potent combined antioxidant effect on the intestine and liver in experimental obstructive jaundice, significantly prevented intestinal barrier dysfunction and liver injury. The variety of results depending on the antioxidant agent that was administered and the marker of oxidative stress that was estimated, indicates that a battery of biomarkers would be more appropriate in assessing pharmacologic responses to therapeutic interventions.
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Yalinkilic O, Enginar H. Effect of X-Radiation on Lipid Peroxidation and Antioxidant Systems in Rats Treated with Saponin-containing Compounds. Photochem Photobiol 2007; 84:236-42. [DOI: 10.1111/j.1751-1097.2007.00240.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Wei L, Hata K, Doorschodt BM, Büttner R, Minor T, Tolba RH. Experimental small bowel preservation using Polysol: A new alternative to University of Wisconsin solution, Celsior and histidine-tryptophan-ketoglutarate solution? World J Gastroenterol 2007; 13:3684-91. [PMID: 17659727 PMCID: PMC4250639 DOI: 10.3748/wjg.v13.i27.3684] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the potential of Polysol, a newly developed preservation solution, in cold storage of small bowel grafts, compared with the current standards, University of Wisconsin solution (UW), Celsior and histidine-tryptophan-ketoglutarate solution (HTK).
METHODS: Male Wistar rats were used as donors. Small bowels were retrieved, flushed and then stored in the respective 4 solutions for 18 h at 4°C. Functional integrity of the grafts was evaluated by isolated reperfusion with oxygenated Krebs-Henseleit buffer at 37°C for 30 min in all 4 groups.
RESULTS: Polysol preservation exhibited the highest tissue ATP concentration and the lowest release of LDH. Malondialdehyde, an index for tissue lipid peroxidation, was also the lowest in Polysol. Tissue oxygen consumption was significantly higher in Polysol than in the others. Of interest, UW-storage promoted 10-fold higher apoptosis than in the others. Moreover, electron microscopy revealed that the mucosal villi/micro-villi formation and the cell organelles, including mitochondria, were both significantly better preserved in Polysol, while deleterious alterations were apparent in the others, most notably in UW. Although Celsior and HTK exhibited the better trend of results than UW in some parameters, but could not reach the over-all superiority to UW.
CONCLUSION: Cold storage using Polysol resulted in significantly better integrity and function of small bowel grafts than UW. Hence, Polysol may be a novel alternative for the small bowel preservation.
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Affiliation(s)
- Lai Wei
- House of Experimental Therapy, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany
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Enginar H, Cemek M, Karaca T, Unak P. Effect of grape seed extract on lipid peroxidation, antioxidant activity and peripheral blood lymphocytes in rats exposed to x-radiation. Phytother Res 2007; 21:1029-35. [PMID: 17622972 DOI: 10.1002/ptr.2201] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The present studies were designed to evaluate supplemental grape seed extract (GSE) and vitamin E supplements on lipid peroxidation, on antioxidant systems and peripheral blood lymphocytes in rats exposed to x-rays. Three groups of rats were investigated: a control group (CG) received intraperitoneal (i.p.) physiological serum 1 mL/day (n=10), i.p.; a vitamin E group (VG) received 50 mg/kg/day (n=10); an i.p. grape seed extract group received 50 mg/kg/day (n=10). Four weeks later, a 6 Gy radiation dose was given to the rats. Blood samples were taken 24 h later after irradiation and lymphocyte, malondialdehyde (MDA), reduced glutathione (GSH), nitrate, nitrite, reduced ascorbic acid, retinol, beta-carotene and ceruloplasmin concentrations were analysed. The levels of GSH (p<0.05), retinol (p<0.001), beta-carotene (p<0.05) and ceruloplasmin concentration (p<0.001) in the GSE group were found to be higher than in the control group but the level of MDA (p<0.001) and nitrite concentration (p<0.05) in rats supplemented with GSE were found to be lower than in the control group. The results indicate that GSE enhanced the antioxidant status and decreased the incidence of free radical-induced lipid peroxidation in blood samples of rats exposed to x-radiation. The antioxidant effect of GSE given to animals was more effective than vitamin E administered before whole-body irradiation in rats.
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Affiliation(s)
- Hüseyin Enginar
- Department of Chemistry, Afyon Kocatepe University, 03200 Afyon, Turkey
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Demirer S, Ulusu NN, Aslim B, Kepenekci I, Ulusoy C, Andrieu MN, Erkek B, Aydintug S. Protective effects of Lactobacillus delbrueckii subsp bulgaricus B3 on intestinal enzyme activities after abdominal irradiation in rats. Nutr Res 2007. [DOI: 10.1016/j.nutres.2007.02.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Uemura T, Nakayama T, Kusaba T, Yakata Y, Yamazumi K, Matsuu-Matsuyama M, Shichijo K, Sekine I. The protective effect of interleukin-11 on the cell death induced by X-ray irradiation in cultured intestinal epithelial cell. JOURNAL OF RADIATION RESEARCH 2007; 48:171-7. [PMID: 17380044 DOI: 10.1269/jrr.06047] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
Interleukin-11 (IL-11) is a well known anti-inflammatory cytokine that is associated with cell growth, and also participates in limiting X-ray irradiation induced intestinal mucosal injury. The aim of this study was to evaluate the protective effect of IL-11 on the cell injury induced by X-ray irradiation in rat intestinal epithelial IEC-18 cells. Recombinant human IL-11 (rhIL-11) treated cells were irradiated and then examined for cell viability. To evaluate irradiation injury, trypan blue staining was used to detect the dead cells. The viability of irradiated cells was up-regulated by rhIL-11 treatment and also resulted in the activation of p90 ribosomal S6 kinase (p90RSK) and S6 ribosomal protein (S6Rp). Wortmannin, a specific inhibitor of PI3K, suppressed the activation of S6Rp in rhIL-11 treated cells, and decreased the up-regulation of viability by rhIL-11 treatment in irradiated cells. The TUNEL assay was also perfomed to estimate the rate of apoptosis in X-ray induced cell death. There was no difference in the results between trypan blue staining and the TUNEL assay. Further, rhIL-11 down-regulated the expression of cleaved caspase-3 in irradiated cells. These results suggest that rhIL-11 may play an important role in protection from radiation injury.
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Affiliation(s)
- Takashi Uemura
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Japan
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Bese NS, Munzuroglu F, Uslu B, Arbak S, Yesiladali G, Sut N, Altug T, Ober A. Vitamin E protects against the development of radiation-induced pulmonary fibrosis in rats. Clin Oncol (R Coll Radiol) 2007; 19:260-4. [PMID: 17433970 DOI: 10.1016/j.clon.2006.12.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2006] [Revised: 12/01/2006] [Accepted: 12/11/2006] [Indexed: 11/24/2022]
Abstract
AIMS To investigate whether the application of vitamin E with or without pentoxifylline could modify the development of radiation-induced pulmonary fibrosis. MATERIALS AND METHODS Wistar albino rats were supplemented with either vitamin E or pentoxifylline or with both vitamin E and pentoxifylline after a single dose of 14 Gy thoracic irradiation. Supplementation was started the day after irradiation and continued until the rats were sacrificed. As a quantitative end point, the extent of fibrosis was evaluated with a scale from 0 (normal lung) to 8 (total fibrous obliteration of the field) at pathological examination of the lung tissue. RESULTS A significant reduction in fibrosis was obtained in the group of rats supplemented with vitamin E with or without pentoxifylline, when compared with the group that had irradiation only. CONCLUSION This experimental study showed that vitamin E supplementation immediately after irradiation protected rats against radiation-induced pulmonary fibrosis. The combination with pentoxifylline was more effective, although pentoxifylline itself had limited efficacy, which was not statistically significant.
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Affiliation(s)
- N S Bese
- Department of Radiation Oncology, Cerrahpasa Medical School, Istanbul University, 34098 Cerrahpasa, Istanbul, Turkey.
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Cemek M, Enginar H, Karaca T, Ünak P. In Vivo Radioprotective Effects of Nigella sativa L Oil and Reduced Glutathione Against Irradiation-Induced Oxidative Injury and Number of Peripheral Blood Lymphocytes in Rats. Photochem Photobiol 2006. [DOI: 10.1111/j.1751-1097.2006.tb09832.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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