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BioMed Research International 2014Nowadays, radiotherapy has become an integral part of the treatment regimen in various malignancies for curative or palliative purposes. Ionizing radiation interacts... (Review)
Review
Nowadays, radiotherapy has become an integral part of the treatment regimen in various malignancies for curative or palliative purposes. Ionizing radiation interacts with biological systems to produce free radicals, which attack various cellular components. Radioprotectors act as prophylactic agents that are administered to shield normal cells and tissues from the harmful effects of radiation. Melatonin has been shown to be both a direct free radical scavenger and an indirect antioxidant by stimulating antioxidant enzymes and suppressing prooxidative enzymes activity. In addition to its antioxidant property, there have also been reports implicating antiapoptotic function for melatonin in normal cells. Furthermore, through its antitumor and radiosensitizing properties, treatment with melatonin may prevent tumor progression. Therefore, addition of melatonin to radiation therapy could lower the damage inflicted to the normal tissue, leading to a more efficient tumor control by use of higher doses of irradiation during radiotherapy. Thus, it seems that, in the future, melatonin may improve the therapeutic gain in radiation oncology treatments.
Topics: Animals; Antioxidants; Apoptosis; Free Radical Scavengers; Humans; Melatonin; Radiation Oncology; Radiation-Protective Agents
PubMed: 24900972
DOI: 10.1155/2014/578137 -
Biochimica Et Biophysica Acta.... Feb 2019Cyanobacteria are thought to be responsible for pioneering dioxygen production and the so-called "Great Oxygenation Event" that determined the formation of the ozone...
Cyanobacteria are thought to be responsible for pioneering dioxygen production and the so-called "Great Oxygenation Event" that determined the formation of the ozone layer and the ionosphere restricting ionizing radiation levels reaching our planet, which increased biological diversity but also abolished the necessity of radioprotection. We speculated that ancient protection mechanisms could still be present in cyanobacteria and studied the effect of ionizing radiation and space flight during the Foton-M4 mission on Synechocystis sp. PCC6803. Spectral and functional characteristics of photosynthetic membranes revealed numerous similarities of the effects of α-particles and space flight, which both interrupted excitation energy transfer from phycobilisomes to the photosystems and significantly reduced the concentration of phycobiliproteins. Although photosynthetic activity was severely suppressed, the effect was reversible, and the cells could rapidly recover from the stress. We suggest that the actual existence and the uncoupling of phycobilisomes may play a specific role not only in photo-, but also in radioprotection, which could be crucial for the early evolution of Life on Earth.
Topics: Cyanobacteria; Energy Transfer; Origin of Life; Photosynthesis; Phycobiliproteins; Phycobilisomes; Radiation, Ionizing; Radiation-Protective Agents; Space Flight
PubMed: 30465750
DOI: 10.1016/j.bbabio.2018.11.018 -
Life Sciences in Space Research Nov 2022As humanity begins to venture further into space, approaches to better protect astronauts from the hazards found in space need to be developed. One particular hazard of... (Review)
Review
As humanity begins to venture further into space, approaches to better protect astronauts from the hazards found in space need to be developed. One particular hazard of concern is the complex radiation that is ever present in deep space. Currently, it is unlikely enough spacecraft shielding could be launched that would provide adequate protection to astronauts during long-duration missions such as a journey to Mars and back. In an effort to identify other means of protection, prophylactic radioprotective drugs have been proposed as a potential means to reduce the biological damage caused by this radiation. Unfortunately, few radioprotectors have been approved by the FDA for usage and for those that have been developed, they protect normal cells/tissues from acute, high levels of radiation exposure such as that from oncology radiation treatments. To date, essentially no radioprotectors have been developed that specifically counteract the effects of chronic low-dose rate space radiation. This review highlights how high-throughput screening (HTS) methodologies could be implemented to identify such a radioprotective agent. Several potential target, pathway, and phenotypic assays are discussed along with potential challenges towards screening for radioprotectors. Utilizing HTS strategies such as the ones proposed here have the potential to identify new chemical scaffolds that can be developed into efficacious radioprotectors that are specifically designed to protect astronauts during deep space journeys. The overarching goal of this review is to elicit broader interest in applying drug discovery techniques, specifically HTS towards the identification of radiation countermeasures designed to be efficacious towards the biological insults likely to be encountered by astronauts on long duration voyages.
Topics: Humans; Cosmic Radiation; Space Flight; High-Throughput Screening Assays; Astronauts; Spacecraft; Radiation-Protective Agents; Radiation Dosage
PubMed: 36336374
DOI: 10.1016/j.lssr.2022.07.004 -
TheScientificWorldJournal 2015Humans have been using natural products for medicinal use for ages. Natural products of therapeutic importance are compounds derived from plants, animals, or any... (Review)
Review
Humans have been using natural products for medicinal use for ages. Natural products of therapeutic importance are compounds derived from plants, animals, or any microorganism. Ginger is also one of the most commonly used condiments and a natural drug in vogue. It is a traditional medicine, having some active ingredients used for the treatment of numerous diseases. During recent research on ginger, various ingredients like zingerone, shogaol, and paradol have been obtained from it. Zingerone (4-(4-hydroxy-3-methoxyphenyl)-2-butanone) is a nontoxic and inexpensive compound with varied pharmacological activities. It is the least pungent component of Zingiber officinale. Zingerone is absent in fresh ginger but cooking or heating transforms gingerol to zingerone. Zingerone closely related to vanillin from vanilla and eugenol from clove. Zingerone has potent anti-inflammatory, antidiabetic, antilipolytic, antidiarrhoeic, antispasmodic, and so forth properties. Besides, it displays the property of enhancing growth and immune stimulation. It behaves as appetite stimulant, anxiolytic, antithrombotic, radiation protective, and antimicrobial. Also, it inhibits the reactive nitrogen species which are important in causing Alzheimer's disease and many other disorders. This review is written to shed light on the various pharmacological properties of zingerone and its role in alleviating numerous human and animal diseases.
Topics: Animals; Anti-Inflammatory Agents; Antidiarrheals; Antiemetics; Antineoplastic Agents; Antioxidants; Zingiber officinale; Guaiacol; Humans; Lipolysis; Plant Extracts; Radiation-Protective Agents
PubMed: 26106644
DOI: 10.1155/2015/816364 -
Roczniki Panstwowego Zakladu Higieny 2014Ionizing radiation may cause damage to living tissue by producing free radicals like reactive oxygen species (ROS). ROS can randomly react with lipids, proteins and... (Review)
Review
UNLABELLED
Ionizing radiation may cause damage to living tissue by producing free radicals like reactive oxygen species (ROS). ROS can randomly react with lipids, proteins and nucleic acids of cell causing oxidative stress and damage in these macromolecules, leading to pathogenesis of chronic diseases and age related and also cancer. The first line of defense from the damaging effects of ROS is antioxidants, which convert the oxidants to less reactive species. Lycopene (LYC) is an acyclic isomer of beta-carotene. It synthesized by plants or autotrophic bacteria but not by animals. Red fruits and vegetables, including tomatoes, watermelons, pink grapefruits, apricots, pink guavas and papaya contain LYC. This carotenoid has very strong antioxidant properties. The many studies confirm that dietary supplementation with LYC reduces risk of cancers of many organs, but also retard the growth of the tumors. LYC has also chemopreventive effects against other diseases such as cardiovascular disease, osteoporosis, male infertility and inhibits the toxic action of other agents. Numerous in vitro and animal studies showed that LYC may provide protection against damages induced by ionizing radiation. It suggests that supplementation of LYC might be useful in diminishing of negative effect of cancer radiotherapy or in mitigating the effects of possible radiation accidents on human health.
KEY WORDS
lycopene, antioxidants, anticarcinogenic agents, radioprotection.
Topics: Anticarcinogenic Agents; Antioxidants; Cardiovascular Diseases; Carotenoids; Humans; Lycopene; Solanum lycopersicum; Neoplasms; Radiation-Protective Agents
PubMed: 25526570
DOI: No ID Found -
Molecules (Basel, Switzerland) Oct 2009The 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... (Review)
Review
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.
Topics: Cytoprotection; Humans; Lymphedema; Neoplasms; Radiation-Protective Agents; Randomized Controlled Trials as Topic; Selenium
PubMed: 19924043
DOI: 10.3390/molecules14103975 -
Journal of Radiation Research Mar 2001
Review
Topics: Animals; Cytokines; Cytoprotection; Free Radical Scavengers; Humans; Radiation-Protective Agents; Radiotherapy
PubMed: 11393887
DOI: 10.1269/jrr.42.21 -
BMC Pharmacology & Toxicology Mar 2021This study aimed to confirm the cytotoxicity of zymosan in vitro and in vivo and determine the appropriate treatment time and the dose of zymosan.
BACKGROUND
This study aimed to confirm the cytotoxicity of zymosan in vitro and in vivo and determine the appropriate treatment time and the dose of zymosan.
METHODS
AHH-1 cells and HIECs were administered by 0, 20, 40, 80 or 160 μg/mL zymosan. The CCK-8 assay and flow cytometry were used to evaluate the cell viability and apoptosis 24 h, 48 h, and 72 h after administration. Furthermore, 12 h before irradiation, the cells were treated with 0, 5, 10, or 20 μg/mL zymosan and then irradiated with 4 Gy X-rays. Cell viability and apoptosis were measured by the CCK-8 assay and flow cytometry at 24 h. In addition, the protective effect of zymosan against radiation in vitro was compared to that of 20 μg/mL LPS. In vivo, weight, the spleen index, and the thymus index were measured to evaluate the toxicity of 0, 5, 10, 20, and 10 mg/kg zymosan. In addition, rats were treated with 0, 2, 4, 8, or 10 mg/kg zymosan and then irradiated with 7 Gy X-rays. The survival rate, organ index were evaluated. The protective effect of zymosan against radiation in vivo was compared to that of 10 mg/kg LPS a positive control.
RESULTS
The viability and apoptosis of cells treated with different doses and treatment times of zymosan were not different from those of control cells (p < 0.05). Furthermore, cell viability and apoptosis were clearly improved after zymosan preadministration (p < 0.05). The radioprotective effect of zymosan was dose-dependent. In addition, the viability of cells pretreated with zymosan was higher than that of cells pretreated with LPS, and the apoptosis rate of zymosan-treated cells was lower than that of cells pretreated with LPS (p < 0.05). In vivo, weight, the spleen index and the thymus index were significantly decreased by zymosan at a concentration of 20 mg/kg (p < 0.05). Further experiments showed that the concentration at which zymosan exerted radioprotective effects was 10 mg/kg. The survival curves in the irradiated rats were barely separated between the LPS treatment and zymosan treatment.
CONCLUSION
Zymosan administration before radiation exposure significantly increased cell viability and the survival rates of rats.
Topics: Animals; Apoptosis; Cell Line; Cell Survival; Humans; Lipopolysaccharides; Male; Radiation-Protective Agents; Rats, Sprague-Dawley; X-Rays; Zymosan; Rats
PubMed: 33731220
DOI: 10.1186/s40360-021-00482-1 -
Expert Opinion on Drug Discovery Jul 2017Despite significant scientific advances over the past six decades toward the development of safe and effective radiation countermeasures for humans using animal models,... (Review)
Review
Despite significant scientific advances over the past six decades toward the development of safe and effective radiation countermeasures for humans using animal models, only two pharmaceutical agents have been approved by United States Food and Drug Administration (US FDA) for hematopoietic acute radiation syndrome (H-ARS). Additional research efforts are needed to further develop large animal models for improving the prediction of clinical safety and effectiveness of radiation countermeasures for ARS and delayed effects of acute radiation exposure (DEARE) in humans. Area covered: The authors review the suitability of animal models for the development of radiation countermeasures for ARS following the FDA Animal Rule with a special focus on nonhuman primate (NHP) models of ARS. There are seven centers in the United States currently conducting studies with irradiated NHPs, with the majority of studies being conducted with rhesus monkeys. Expert opinion: The NHP model is considered the gold standard animal model for drug development and approval by the FDA. The lack of suitable substitutes for NHP models for predicting response in humans serves as a bottleneck for the development of radiation countermeasures. Additional large animal models need to be characterized to support the development and FDA-approval of new radiation countermeasures.
Topics: Acute Radiation Syndrome; Animals; Disease Models, Animal; Drug Approval; Drug Design; Drug Discovery; Humans; Macaca mulatta; Primates; Radiation-Protective Agents; United States; United States Food and Drug Administration
PubMed: 28441902
DOI: 10.1080/17460441.2017.1323863 -
International Journal of Radiation... Jan 2019The risk of radiation exposure is considered to have increased in recent years. For convenience and simple administration, development of an effective orally...
17α-Ethinyl-androst-5-ene-3β, 17β-diol, a Novel Potent Oral Radioprotective Agent, Confers Radioprotection of Hematopoietic Stem and Progenitor Cells in a Granulocyte Colony-Stimulating Factor-Independent Manner.
PURPOSE
The risk of radiation exposure is considered to have increased in recent years. For convenience and simple administration, development of an effective orally administered radioprotective agent is highly desirable. The steroid 5-androstene-3β, 17β-diol (5-AED) has been evaluated as both a radioprotector and a radiomitigator in mice and nonhuman primates; however, poor oral bioavailability has limited its development. A variant compound-17α-ethinyl-androst-5-ene-3β, 17β-diol (EAD)-exhibits significant oral bioavailability. We investigated the radioprotective effects of EAD via oral administration in mice.
METHODS AND MATERIALS
Survival assays were performed in lethally (9.0-10.0 Gy) irradiated mice. Peripheral blood cell counts were monitored in lethally (9.5 Gy) or sublethally (6.5 Gy) irradiated mice. We performed histologic analysis of bone marrow (BM) and frequency and functional analysis of hematopoietic stem and progenitor cells in mice irradiated with 6.5 Gy. To investigate multilineage engraftment of irradiated hematopoietic stem cells after BM transplantation, competitive repopulation assays were conducted. Plasma granulocyte colony-stimulating factor was measured by enzyme-linked immunosorbent assay.
RESULTS
Oral administration of EAD on 3 consecutive days before irradiation conferred 100% survival in mice, against otherwise 100% death, at a 9.5-Gy lethal dose of total body irradiation. EAD ameliorated radiation-induced pancytopenia at the same dose. EAD augmented BM cellular recovery and colony-forming ability, promoted hematopoietic stem and progenitor cell recovery, and expanded the pool of functionally superior hematopoietic stem cells in the BM of sublethally irradiated mice. Unlike 5-AED, EAD did not increase granulocyte colony-stimulating factor levels in mice and exhibited no therapeutic effects on hematologic recovery after irradiation; nevertheless, its radioprotective efficacy was superior to that of 5-AED.
CONCLUSIONS
Our findings demonstrate the radioprotective efficacy of EAD and reveal that the 17α-ethinyl group is essential for its oral activity. Given its oral efficacy and low toxicity, EAD has potential as an optimal radioprotector for use by first responders, as well as at-risk civilian populations.
Topics: Animals; Bone Marrow Transplantation; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells; Male; Mice; Mice, Inbred C57BL; Radiation-Protective Agents; Whole-Body Irradiation
PubMed: 30103023
DOI: 10.1016/j.ijrobp.2018.08.002