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Nutrients May 2020Vitamin C has been known for decades. It is common in everyday use as an element of the diet, supplementation, and a preservative. For years, research has been conducted... (Review)
Review
Vitamin C has been known for decades. It is common in everyday use as an element of the diet, supplementation, and a preservative. For years, research has been conducted to precisely determine the mechanism of action of ascorbate in the cell. Available results indicate its multi-directional cellular effects. Vitamin C, which belongs to antioxidants scavenging free radicals, also has a 'second face'-as a pro-oxidative factor. However, whether is the latter nature a defect harmful to the cell, or whether a virtue that is a source of benefit? In this review, we discuss the effects of vitamin C treatment in cancer prevention and the role of ascorbate in maintaining redox balance in the central nervous system (CNS). Finally, we discuss the effect of vitamin C supplementation on biomarkers of oxidative DNA damage and review the evidence that vitamin C has radioprotective properties.
Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Biomarkers; Central Nervous System; DNA Damage; Free Radicals; Humans; Neoplasms; Oxidants; Oxidation-Reduction; Oxidative Stress; Radiation-Protective Agents
PubMed: 32455696
DOI: 10.3390/nu12051501 -
Journal of the American Academy of... May 2021Cutaneous photobiology studies have focused primarily on the ultraviolet portion of the solar spectrum. Visible light (VL), which comprises 50% of the electromagnetic... (Review)
Review
Cutaneous photobiology studies have focused primarily on the ultraviolet portion of the solar spectrum. Visible light (VL), which comprises 50% of the electromagnetic radiation that reaches the Earth's surface and, as discussed in Part I of this CME, has cutaneous biologic effects, such as pigment darkening and erythema. Photoprotection against VL includes avoiding the sun, seeking shade, and using photoprotective clothing. The organic and inorganic ultraviolet filters used in sunscreens do not protect against VL, only tinted sunscreens do. In the United States, these filters are regulated by the Food and Drug Administration as an over-the-counter drug and are subject to more stringent regulations than in Europe, Asia, and Australia. There are no established guidelines regarding VL photoprotection. Alternative measures to confer VL photoprotection are being explored. These novel methods include topical, oral, and subcutaneous agents. Further development should focus on better protection in the ultraviolet A1 (340-400 nm) and VL ranges while enhancing the cosmesis of the final products.
Topics: Administration, Cutaneous; Administration, Oral; Erythema; Humans; Injections, Subcutaneous; Radiation-Protective Agents; Skin; Skin Pigmentation; Sunlight; Treatment Outcome; Ultraviolet Rays
PubMed: 33640513
DOI: 10.1016/j.jaad.2020.11.074 -
International Journal of Molecular... Apr 2017There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms... (Review)
Review
There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms underpinning these inhibitory actions have been proposed. What is rather perplexing, however, is the large number of processes by which melatonin reportedly restrains cancer development and growth. These diverse actions suggest that what is being observed are merely epiphenomena of an underlying more fundamental action of melatonin that remains to be disclosed. Some of the arresting actions of melatonin on cancer are clearly membrane receptor-mediated while others are membrane receptor-independent and involve direct intracellular actions of this ubiquitously-distributed molecule. While the emphasis of melatonin/cancer research has been on the role of the indoleamine in restraining breast cancer, this is changing quickly with many cancer types having been shown to be susceptible to inhibition by melatonin. There are several facets of this research which could have immediate applications at the clinical level. Many studies have shown that melatonin's co-administration improves the sensitivity of cancers to inhibition by conventional drugs. Even more important are the findings that melatonin renders cancers previously totally resistant to treatment sensitive to these same therapies. Melatonin also inhibits molecular processes associated with metastasis by limiting the entrance of cancer cells into the vascular system and preventing them from establishing secondary growths at distant sites. This is of particular importance since cancer metastasis often significantly contributes to death of the patient. Another area that deserves additional consideration is related to the capacity of melatonin in reducing the toxic consequences of anti-cancer drugs while increasing their efficacy. Although this information has been available for more than a decade, it has not been adequately exploited at the clinical level. Even if the only beneficial actions of melatonin in cancer patients are its ability to attenuate acute and long-term drug toxicity, melatonin should be used to improve the physical wellbeing of the patients. The experimental findings, however, suggest that the advantages of using melatonin as a co-treatment with conventional cancer therapies would far exceed improvements in the wellbeing of the patients.
Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Transformation, Neoplastic; DNA Damage; Disease Progression; Drug Resistance, Neoplasm; Genomic Instability; Humans; Melatonin; Neoplasm Metastasis; Neoplasms; Radiation-Protective Agents; Treatment Outcome
PubMed: 28420185
DOI: 10.3390/ijms18040843 -
Nature Communications Mar 2022Protecting the whole small intestine from radiation-induced intestinal injury during the radiotherapy of abdominal or pelvic solid tumors remains an unmet clinical need....
Protecting the whole small intestine from radiation-induced intestinal injury during the radiotherapy of abdominal or pelvic solid tumors remains an unmet clinical need. Amifostine is a promising selective radioprotector for normal tissues. However, its oral application in intestinal radioprotection remains challenging. Herein, we use microalga Spirulina platensis as a microcarrier of Amifostine to construct an oral delivery system. The system shows comprehensive drug accumulation and effective radioprotection in the whole small intestine that is significantly superior to free drug and its enteric capsule, preventing the radiation-induced intestine injury and prolonging the survival without influencing the tumor regression. It also shows benefits on the gut microbiota homeostasis and long-term safety. Based on a readily available natural microcarrier, this work presents a convenient oral delivery system to achieve effective radioprotection for the whole small intestine, providing a competitive strategy with great clinical translation potential.
Topics: Gastrointestinal Microbiome; Homeostasis; Humans; Intestines; Microalgae; Neoplasms; Radiation-Protective Agents
PubMed: 35301299
DOI: 10.1038/s41467-022-28744-4 -
Gut Microbes Jul 2020Hematopoietic and intestinal systems side effects are frequently found in patients who suffered from accidental or medical radiation exposure. In this case, we...
BACKGROUND
Hematopoietic and intestinal systems side effects are frequently found in patients who suffered from accidental or medical radiation exposure. In this case, we investigated the effects of gut microbiota produced-valeric acid (VA) on radiation-induced injuries.
METHODS
Mice were exposed to total body irradiation (TBI) or total abdominal irradiation (TAI) to mimic accidental or clinical scenarios. High-performance liquid chromatography (HPLC) was performed to assess short-chain fatty acids (SCFAs) in fecal pellets. Oral gavage with VA was used to mitigate radiation-induced toxicity. Gross examination was performed to assess tissue injuries of thymus, spleen and small intestine. High-throughput sequencing was used to characterize the gut microbiota profile. Isobaric tags for relative and absolute quantitation (iTRAQ) were performed to analyze the difference of protein profile. Hydrodynamic-based gene delivery assay was performed to silence KRT1 .
RESULTS
VA exerted the most significant radioprotection among the SCFAs. In detail, VA replenishment elevated the survival rate of irradiated mice, protected hematogenic organs, improved gastrointestinal (GI) tract function and intestinal epithelial integrity in irradiated mice. High-throughput sequencing and iTRAQ showed that oral gavage of VA restored the enteric bacteria taxonomic proportions, reprogrammed the small intestinal protein profile of mice following TAI exposure. Importantly, keratin 1 (KRT1) played a pivotal role in the radioprotection of VA.
CONCLUSIONS
Our findings provide new insights into gut microbiota-produced VA and underpin that VA might be employed as a therapeutic option to mitigate radiation injury in pre-clinical settings.
Topics: Animals; Bacterial Physiological Phenomena; Colitis; Dextran Sulfate; Enteritis; Fatty Acids, Volatile; Female; Gastrointestinal Microbiome; Hematopoietic System; Intestinal Mucosa; Intestine, Small; Intestines; Keratin-1; Male; Mice; Mice, Inbred C57BL; Pentanoic Acids; Proteins; Radiation Injuries, Experimental; Radiation-Protective Agents; Symbiosis
PubMed: 31931652
DOI: 10.1080/19490976.2019.1709387 -
Cell Death & Disease Dec 2019Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy, whereas no effective interventions are available....
Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy, whereas no effective interventions are available. Andrographolide, an active component extracted from Andrographis paniculate, is prescribed as a treatment for upper respiratory tract infection. Here we report the potential radioprotective effect and mechanism of Andrographolide on RILI. C57BL/6 mice were exposed to 18 Gy of whole thorax irradiation, followed by intraperitoneal injection of Andrographolide every other day for 4 weeks. Andrographolide significantly ameliorated radiation-induced lung tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine release in the early phase and progressive fibrosis in the late phase. Moreover, Andrographolide markedly hampered radiation-induced activation of the AIM2 inflammasome and pyroptosis in vivo. Furthermore, bone marrow-derived macrophages (BMDMs) were exposed to 8 Gy of X-ray radiation in vitro and Andrographolide significantly inhibited AIM2 inflammasome mediated-pyroptosis in BMDMs. Mechanistically, Andrographolide effectively prevented AIM2 from translocating into the nucleus to sense DNA damage induced by radiation or chemotherapeutic agents in BMDMs. Taken together, Andrographolide ameliorates RILI by suppressing AIM2 inflammasome mediated-pyroptosis in macrophage, identifying Andrographolide as a novel potential protective agent for RILI.
Topics: Abnormalities, Radiation-Induced; Animals; DNA-Binding Proteins; Disease Models, Animal; Diterpenes; Humans; Inflammasomes; Inflammation; Lung; Lung Injury; Mice; Pyroptosis; Radiation-Protective Agents
PubMed: 31862870
DOI: 10.1038/s41419-019-2195-8 -
Experimental & Molecular Medicine Sep 2017Flagellin is a subunit protein of the flagellum, a whip-like appendage that enables bacterial motility. Traditionally, flagellin was viewed as a virulence factor that... (Review)
Review
Flagellin is a subunit protein of the flagellum, a whip-like appendage that enables bacterial motility. Traditionally, flagellin was viewed as a virulence factor that contributes to the adhesion and invasion of host cells, but now it has emerged as a potent immune activator, shaping both the innate and adaptive arms of immunity during microbial infections. In this review, we summarize our understanding of bacterial flagellin and host immune system interactions and the role flagellin as an adjuvant, anti-tumor and radioprotective agent, and we address important areas of future research interests.
Topics: Adjuvants, Immunologic; Animals; Bacteria; Bacterial Physiological Phenomena; Bacterial Vaccines; Flagellin; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Immune System; Immunomodulation; Immunotherapy; Mucous Membrane; Neoplasms; Radiation-Protective Agents; Signal Transduction
PubMed: 28860663
DOI: 10.1038/emm.2017.172 -
Biomedicine & Pharmacotherapy =... Oct 2020In recent years, many studies have shown that hydrogen has therapeutic and preventive effects on various diseases. Its selective antioxidant properties were well... (Review)
Review
In recent years, many studies have shown that hydrogen has therapeutic and preventive effects on various diseases. Its selective antioxidant properties were well noticed. Most of the ionizing radiation-induced damage is caused by hydroxyl radicals (OH) from radiolysis of HO. Since hydrogen can mitigate such damage through multiple mechanisms, it presents noteworthy potential as a novel radio-protective agent. This review analyses possible mechanisms for hydrogen's radioprotective properties and effective delivery methods. We also look into details of vitro and vivo studies for hydrogen's radioprotective effects, and clinical practices. We conclude that hydrogen has good potential in radio-protection, with evidence that warrants greater research efforts in this field.
Topics: Animals; Humans; Hydrogen; Radiation Injuries; Radiation, Ionizing; Radiation-Protective Agents
PubMed: 32763820
DOI: 10.1016/j.biopha.2020.110589 -
Molecular Medicine Reports Mar 2023A series of physiological and pathological changes occur after radiotherapy and accidental exposure to ionizing radiation (IR). These changes cause serious damage to... (Review)
Review
A series of physiological and pathological changes occur after radiotherapy and accidental exposure to ionizing radiation (IR). These changes cause serious damage to human tissues and can lead to death. Radioprotective countermeasures are radioprotective agents that prevent and reduce IR injury or have therapeutic effects. Based on a good understanding of radiobiology, a number of protective agents have achieved positive results in early clinical trials. The present review grouped known radioprotective agents according to biochemical categories and potential clinical use, and reviewed radiation countermeasures, i.e., radioprotectors, radiation mitigators and radiotherapeutic agents, with an emphasis on their current status and research progress. The aim of the present review is to facilitate the selection and application of suitable radioprotectors for clinicians and researchers, to prevent or reduce IR injury.
Topics: Humans; Radiation Injuries; Radiation Protection; Radiation-Protective Agents; Radiation, Ionizing
PubMed: 36799170
DOI: 10.3892/mmr.2023.12953 -
Archives of Pharmacal Research Nov 2018Radiotherapy is one of the most efficient ways to treat cancer. However, deleterious effects, such as acute and chronic toxicities that reduce the quality of life, may... (Review)
Review
Radiotherapy is one of the most efficient ways to treat cancer. However, deleterious effects, such as acute and chronic toxicities that reduce the quality of life, may result. Naturally occurring compounds have been shown to be non-toxic over wide dose ranges and are inexpensive and effective. Additionally, pharmacological strategies have been developed that use radioprotectors to inhibit radiation-induced toxicities. Currently available radioprotectors have several limitations, including toxicity. In this review, we present the mechanisms of proven radioprotectors, ranging from free radical scavenging (the best-known mechanism of radioprotection) to molecular-based radioprotection (e.g., upregulating expression of heat shock proteins). Finally, we discuss naturally occurring compounds with radioprotective properties in the context of these mechanisms.
Topics: Animals; Apoptosis; Biological Products; DNA Repair; Free Radicals; Humans; Neoplasms; Quality of Life; Radiation Injuries; Radiation-Protective Agents; Radiotherapy
PubMed: 30361949
DOI: 10.1007/s12272-018-1083-6