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Molecules (Basel, Switzerland) Dec 2020Patients receiving brain radiotherapy may suffer acute or chronic side effects. Ionizing radiation induces the production of intracellular reactive oxygen species and... (Review)
Review
Patients receiving brain radiotherapy may suffer acute or chronic side effects. Ionizing radiation induces the production of intracellular reactive oxygen species and pro-inflammatory cytokines in the central nervous system, leading to brain damage. Complementary Chinese herbal medicine therapy may reduce radiotherapy-induced side effects. Flavonoids are a class of natural products which can be extracted from Chinese herbal medicine and have been shown to have neuroprotective and radioprotective properties. Flavonoids are effective antioxidants and can also inhibit regulatory enzymes or transcription factors important for controlling inflammatory mediators, affect oxidative stress through interaction with DNA and enhance genomic stability. In this paper, radiation-induced brain damage and the relevant molecular mechanism were summarized. The radio-neuro-protective effect of flavonoids, i.e., antioxidant, anti-inflammatory and maintaining genomic stability, were then reviewed. We concluded that flavonoids treatment may be a promising complementary therapy to prevent radiotherapy-induced brain pathophysiological changes and cognitive impairment.
Topics: Animals; Brain; Drugs, Chinese Herbal; Flavonoids; Humans; Radiation Injuries; Radiation, Ionizing; Radiation-Protective Agents
PubMed: 33287417
DOI: 10.3390/molecules25235719 -
Molecules (Basel, Switzerland) Feb 2021Sunlight has a long list of positive effects on living beings [...].
Sunlight has a long list of positive effects on living beings [...].
Topics: Biological Products; Humans; Radiation-Protective Agents; Skin
PubMed: 33672187
DOI: 10.3390/molecules26041189 -
Drug Discovery Today Jan 2021High doses of total-body or partial-body radiation exposure can result in a life-threatening acute radiation syndrome as manifested by severe morbidity. Entolimod... (Review)
Review
High doses of total-body or partial-body radiation exposure can result in a life-threatening acute radiation syndrome as manifested by severe morbidity. Entolimod (CBLB502) is effective in protecting against, and mitigating the development of, the hematopoietic and gastrointestinal subsyndromes of the acute radiation syndrome in rodents and nonhuman primates. Entolimod treatment reduces radiation-induced apoptosis and accelerates the regeneration of progenitors in radiation-damaged tissues. The drug has been evaluated clinically for its pharmacokinetics (PK), toxicity, and biomarkers. The US Food and Drug Administration (FDA) has granted investigational new drug, fast-track, and orphan drug statuses to entolimod. Its safety, efficacy, and animal-to-human dose conversion data allowed its progression with a pre-emergency use authorization application submission.
Topics: Acute Radiation Syndrome; Animals; Drug Development; Humans; Peptides; Radiation Exposure; Radiation-Protective Agents
PubMed: 33065293
DOI: 10.1016/j.drudis.2020.10.003 -
Design and evaluation of a novel flavonoid-based radioprotective agent utilizing monoglucosyl rutin.Journal of Radiation Research May 2018In this study, three novel flavonoid composite materials, created by combining an aglycone [quercetin (QUE), hesperetin (HES) or naringenin (NAR)] with monoglucosyl...
In this study, three novel flavonoid composite materials, created by combining an aglycone [quercetin (QUE), hesperetin (HES) or naringenin (NAR)] with monoglucosyl rutin (MGR), were designed to test for improved radioprotectivity compared with that provided by administration of MGR alone. Aglycone in the MGR-composite state was highly soluble in water, compared with aglycone alone dissolved in dimethyl sulfoxide or distilled water. The antioxidant activity of the three flavonoid composites was as high as that of MGR only. Next, the cytotoxicity test after 30 min treatment of an MGR composite showed a clear reduction in cell viability and suggested that a rapid introduction of aglycone into cells had taken place. In addition, QUE/MGR and HES/MGR composites strongly scavenged intracellular reactive oxygen species (ROS) induced by X-ray irradiation as well as MGR alone did. However, in the colony-formation assay using irradiated Chinese hamster ovary (CHO) cells, the HES/MGR composite showed a stronger radioprotective effect than MGR alone did, but the QUE/MGR composite showed no additional protective effect compared with the control. Furthermore, it was revealed that QUE and QUE/MGR composite treatment had the effect of reducing the glutathione (GSH) content in cells, and that QUE showed a stronger inhibition of PARP activity compared that of HES and NAR. Our data demonstrated that when designing a flavonoid composite as a radioprotective agent, it was necessary to select an appropriate aglycone, considering not only its antioxidant ability but also its inhibitory effect on cell recovery or DNA repair after radiation injury.
Topics: Animals; Antioxidants; Biphenyl Compounds; CHO Cells; Cell Survival; Colony-Forming Units Assay; Cricetinae; Cricetulus; Flavonoids; Free Radical Scavengers; Glutathione; Intracellular Space; Picrates; Poly(ADP-ribose) Polymerases; Radiation-Protective Agents; Reactive Oxygen Species; Rutin; Solubility; Time Factors; Water
PubMed: 29373678
DOI: 10.1093/jrr/rrx090 -
Advances in Experimental Medicine and... 2011Inhibitors of histone deacetylases (HDACs) have emerged as a new class of anticancer agents based on their actions in cancer cell growth and cell cycle arrest, terminal... (Review)
Review
Inhibitors of histone deacetylases (HDACs) have emerged as a new class of anticancer agents based on their actions in cancer cell growth and cell cycle arrest, terminal differentiation, and apoptosis. Previously, we rationally designed and developed a new class of hydroxamide- and mercaptoacetamide-bearing HDAC inhibitors. A subset of these inhibitors exhibited chemo-radiation sensitizing properties in various human cancer cells. Furthermore, some HDAC inhibitors protected normal cells from radiation-induced damage and extended the survival of mice following total body exposure to lethal dose radiation. Pathological analyses revealed that intestinal and bone marrow cellularities recovered significantly from radiation-induced damage by structural compartments restoration, suggesting the mechanism of action of these HDAC inhibitors. These findings support the hypothesis that epigenetic regulation may play a crucial role in the functional recovery of normal tissues from radiation injuries.
Topics: Animals; Antineoplastic Agents; DNA Damage; Epigenesis, Genetic; Histone Deacetylase Inhibitors; Humans; Radiation Tolerance; Radiation-Protective Agents; Radiation-Sensitizing Agents
PubMed: 21901627
DOI: 10.1007/978-1-4614-0254-1_14 -
Free Radical Biology & Medicine Jun 2020In mass casualty events involving radiation exposure, there is a substantial unmet need for identifying and developing an orally bioavailable agent that can be used to...
In mass casualty events involving radiation exposure, there is a substantial unmet need for identifying and developing an orally bioavailable agent that can be used to protect the hematopoietic stem cell pool and regenerate hematopoiesis after radiation injury. Dimethyl sulfoxide (DMSO), a free-radical scavenger, has shown therapeutic benefits in many preclinical and clinical studies. This study investigates the radioprotective effects of DMSO on oral administration. Single dose of oral DMSO administrated before irradiation conferred 100% survival of C57BL6/J mice receiving otherwise lethal as well as super-lethal radiation dose, with wide radioprotective time frame (from 15min to 4h). Oral DMSO not only protected radiation-induced acute hematopoietic stem and progenitor cell (HSPC) injury, but also ameliorated long-term BM suppression following irradiation in mice. Mechanistically, DMSO directly protected HSPC survival after irradiation in vitro and in vivo, whereas no radioprotective effect was seen in MLL-AF9-induced leukemia cells. Unexpectedly, DMSO treatment did not inhibit radiation-induced HSPC apoptosis, and the HSPC survival from Trp53-and PUMA-deficient mice after irradiation was also protected by DMSO. In conclusion, our findings demonstrate the radioprotective efficacy of oral DMSO. Given its oral efficacy and little toxicity, DMSO is an attractive candidate for human use in a wide variety of settings, including nuclear accidents and medical radiation.
Topics: Animals; Apoptosis; Dimethyl Sulfoxide; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Mice; Radiation-Protective Agents
PubMed: 32222468
DOI: 10.1016/j.freeradbiomed.2020.03.021 -
Asian Pacific Journal of Cancer... Sep 2021Thymoquinone, has anti-inflammatory, anti-oxidant, and cardio protection properties. This study aimed to evaluate the radioprotective effect of thymoquinone in whole...
BACKGROUND
Thymoquinone, has anti-inflammatory, anti-oxidant, and cardio protection properties. This study aimed to evaluate the radioprotective effect of thymoquinone in whole body X-irradiated rats.
METHODS
This study conducted on 40 male adult Wistar albino rats randomized into the following groups: Group I: Control rats did not receive thymoquinone or ionizing radiation. Group II: Whole-body irradiated rats with 6 Gy of X-ray. Group III: Rats orally intubated with thymoquinone (10 mg/kg/day) for 7 days then subjected to whole-body irradiation with 6 Gy then supplemented with thymoquinone for another 7 days. Group IV: Rats orally intubated with thymoquinone (20 mg/kg/day) for 7 days then subjected to whole-body irradiation with 6 Gy then supplemented with thymoquinone (20 mg/kg/day) for another 7 days. LDH, CK-MB, ALT, AST, MDA, TAC, Catalase activity, GPX, GSR and GSH were measured.
RESULTS
Lipid peroxidation biomarker in the blood of X-irradiated rats significantly increased and accompanied by decrease in the levels of GSH, GSR, GPX, catalase as well as TAC. Moreover, exposure to IR significantly increases cardiac and liver enzymes. However, administration of TQ to X-irradiated rats with either 10 mg/kg or 20 mg/kg have the same reform effects and significantly protects rats against adverse effects of IR.
CONCLUSION
Exposure to X-ray leads to significant changes in cellular biochemical and morphological conditions. Administration of TQ before radiation treatment significantly decreases the adverse effects of IR. TQ can improve cardiac function, decrease myocardial enzyme levels and inhibit oxidative stress.
Topics: Animals; Benzoquinones; Male; Radiation-Protective Agents; Rats; Rats, Wistar; Whole-Body Irradiation; X-Rays
PubMed: 34582673
DOI: 10.31557/APJCP.2021.22.9.3005 -
Environmental Health and Preventive... May 2018Depleted uranium (DU) has been widely applied in industrial and military activities, and is often obtained from producing fuel for nuclear reactors. DU may be released... (Review)
Review
Depleted uranium (DU) has been widely applied in industrial and military activities, and is often obtained from producing fuel for nuclear reactors. DU may be released into the environment, polluting air, soil, and water, and is considered to exert both radiological and chemical toxicity. In humans and animals, DU can induce multiple health effects, such as renal tubular necrosis and bone malignancies. This review summarizes the known information on DU's routes of entry, mechanisms of toxicity, and health effects. In addition, we survey the chelating agents used in ameliorating DU toxicity.
Topics: Animals; Chelating Agents; Humans; Inactivation, Metabolic; Radiation-Protective Agents; Uranium
PubMed: 29769021
DOI: 10.1186/s12199-018-0706-3 -
Molecules (Basel, Switzerland) Aug 2021Currently, radiotherapy is one of the most effective strategies to treat cancer. However, deleterious toxicity against normal cells indicate for the need to selectively... (Review)
Review
Currently, radiotherapy is one of the most effective strategies to treat cancer. However, deleterious toxicity against normal cells indicate for the need to selectively protect them. Reactive oxygen and nitrogen species reinforce ionizing radiation cytotoxicity, and compounds able to scavenge these species or enhance antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) should be properly investigated. Antioxidant plant-derived compounds, such as phenols and polyphenols, could represent a valuable alternative to synthetic compounds to be used as radio-protective agents. In fact, their dose-dependent antioxidant/pro-oxidant efficacy could provide a high degree of protection to normal tissues, with little or no protection to tumor cells. The present review provides an update of the current scientific knowledge of polyphenols in pure forms or in plant extracts with good evidence concerning their possible radiomodulating action. Indeed, with few exceptions, to date, the fragmentary data available mostly derive from in vitro studies, which do not find comfort in preclinical and/or clinical studies. On the contrary, when preclinical studies are reported, especially regarding the bioactivity of a plant extract, its chemical composition is not taken into account, avoiding any standardization and compromising data reproducibility.
Topics: Animals; Humans; Polyphenols; Radiation-Protective Agents
PubMed: 34443561
DOI: 10.3390/molecules26164969 -
Asian Pacific Journal of Cancer... 2011Despite good understanding of the molecular basis of the disease and advances in treatment, globally cancer is still a major cause of death. Estimates are that it will... (Review)
Review
Despite good understanding of the molecular basis of the disease and advances in treatment, globally cancer is still a major cause of death. Estimates are that it will surpass cardiovascular disease as the leading cause of death, with higher incidences in the developing countries that have minimal resources. Chemotherapy and radiotherapy, the two most commonly used treatment modalities, are associated with untoward side effects. This has necessitated the search for alternatives that are effective, non toxic and easily affordable for patients and traditional medicinal plants are an ideal source. Eugenia jambolana Lam., commonly known as black plum or 'jamun' is an important medicinal plant in various traditional systems of medicine. It is effective in the treatment of diabetes mellitus, inflammation, ulcers and diarrhea and preclinical studies have also shown it to possess antineoplastic, chemopreventive and radioprotective properties. Here, for the first time, the effects of jamun in treatment and prevention of cancer, and the mechanisms responsible for these effects are appraised. Additionally the drawbacks in existing knowledge are also stressed to emphasize the possible avenues that need to be investigated, so that maximum effects on both prevention and cure can be attained.
Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents; Drug Evaluation, Preclinical; Humans; Neoplasms; Phytotherapy; Plant Extracts; Plants, Medicinal; Radiation-Protective Agents; Syzygium
PubMed: 21517226
DOI: No ID Found