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Review of the evidence of radioprotective potential of creatine and arginine as dietary supplements.International Journal of Radiation... 2024Creatine (Cr) and l-arginine are naturally occurring guanidino compounds, commonly used as ergogenic dietary supplements. Creatine and l-arginine exhibit also a number... (Review)
Review
PURPOSE
Creatine (Cr) and l-arginine are naturally occurring guanidino compounds, commonly used as ergogenic dietary supplements. Creatine and l-arginine exhibit also a number of non-energy-related features, such as antioxidant, anti-apoptotic, and anti-inflammatory properties, which contribute to their protective action against oxidative stress (OS). In this regard, there are a number of studies emphasizing the protective effect of Cr against OS, which develops in the process of aging, increased physical loads as part of athletes' workouts, as well as a number of neurological diseases and toxic effects associated with xenobiotics and UV irradiation. Against this backdrop, and since ionizing radiation causes OS in cells, leading to radiotoxicity, there is an increasing interest to understand whether Cr has the full potential to serve as an effective radioprotective agent. The extensive literature search did not provide any data on this issue. In this narrative review, we have summarized some of our own experimental data published over the last years addressing the respective radioprotective effects of Cr. Next, we have additionally reviewed the existing data on the radiomodifying effects of l-arginine presented earlier by other research groups.
CONCLUSIONS
Creatine possesses significant radioprotective potential including: (1) radioprotective effect on the survival rate of rats subjected to acute whole-body X-ray irradiation in a LD dose of 6.5 Gy, (2) radioprotective effect on the population composition of peripheral blood cells, (3) radioprotective effect on the DNA damage of peripheral blood mononuclear cells, (4) radioprotective effect on the hepatocyte nucleus-nucleolar apparatus, and (5) radioprotective effect on the brain and liver Cr-Cr kinase systems of the respective animals. Taking into account these cytoprotective, gene-protective, hepatoprotective and energy-stimulating features of Cr, as well as its significant radioprotective effect on the survival rate of rats, it can be considered as a potentially promising radioprotector for further preclinical and clinical studies. The review of the currently available data on radiomodifying effects of l-arginine has indicated its significant potential as a radioprotector, radiomitigator, and radiosensitizer. However, to prove the effectiveness of arginine (Arg) as a radioprotective agent, it appears necessary to expand and deepen the relevant preclinical studies, and, most importantly, increase the number of proof-of-concept clinical trials, which are evidently lacking as of now.
Topics: Arginine; Radiation-Protective Agents; Creatine; Dietary Supplements; Animals; Humans; Oxidative Stress
PubMed: 38683545
DOI: 10.1080/09553002.2024.2345098 -
International Journal of Radiation... 2021Our previous study indicated that sodium orthovanadate (vanadate), a strong inhibitor of p53, effectively suppressed the lethality from the hematopoietic (HP) and...
PURPOSE
Our previous study indicated that sodium orthovanadate (vanadate), a strong inhibitor of p53, effectively suppressed the lethality from the hematopoietic (HP) and gastrointestinal (GI) syndromes after 12 Gy total-body irradiation (TBI) in mice. This conclusion, however, was inconsistent with the fact that p53 plays a radioprotective role in the intestinal epithelium. The death after TBI of around 12 Gy was attributed to a combined effect of HP and GI syndromes. To verify the effect from prophylactic administration of p53 inhibitor on protection of HP and GI syndromes, in this study, the radioprotective effects from vanadate were investigated in TBI and lower half-body irradiation (partial-body irradiation: PBI) mouse models.
METHODS
Female ICR mice were given a single injection of vanadate or vehicle, followed by a lethal dose of TBI or PBI. Radioprotective effects of vanadate against the irradiations were evaluated by analyzing survival rate, body weight, hematopoietic parameters, and histological changes in the bone marrow and intestinal epithelium.
RESULTS
TBI-induced HP syndrome was effectively suppressed by vanadate treatment. After TBI, the vanadate-treated mice retained better bone marrow cellularity and showed markedly higher survival rate compared to the vehicle-treated animals. In contrast, vanadate did not relieve loss of intestinal crypts and failed to rescue mice from GI death after PBI.
CONCLUSION
Vanadate is a p53 inhibitor that has been shown to be beneficial as a radiation protective agent against HP but was not effective in protecting against acute GI radiation injury.
Topics: Animals; Bone Marrow; Dose-Response Relationship, Radiation; Gastrointestinal Tract; Mice; Mice, Inbred ICR; Radiation-Protective Agents; Sodium; Tumor Suppressor Protein p53; Vanadates; Whole-Body Irradiation
PubMed: 34125648
DOI: 10.1080/09553002.2021.1941377 -
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 -
Mutagenesis Jul 2005A majority of potential radioprotective synthetic compounds have demonstrated limited clinical application owing to their inherent toxicity, and thus, the seeking of... (Review)
Review
A majority of potential radioprotective synthetic compounds have demonstrated limited clinical application owing to their inherent toxicity, and thus, the seeking of naturally occurring herbal products, such as ginseng, for their radioprotective capability has become an attractive alternative. In general, ginseng refers to the roots of the species of the genus Panax. As a medicinal herb, ginseng has been widely used in traditional Chinese medicine for its wide spectrum of medicinal effects, such as tonic, immunomodulatory, antimutagenic, adaptogenic and antiaging activities. Many of its medicinal effects are attributed to the triterpene glycosides known as ginsenosides (saponins). This review addresses the issue of the radioprotective effects of ginseng on mammalian cells both in vitro and in vivo. Results indicate that the water-soluble extract of whole ginseng appears to give a better protection against radiation-induced DNA damage than does the isolated ginsenoside fractions. Since free radicals play an important role in radiation-induced damage, the underlying radioprotective mechanism of ginseng could be linked, either directly or indirectly, to its antioxidative capability by the scavenging free radicals responsible for DNA damage. In addition, ginseng's radioprotective potential may also be related to its immunomodulating capabilities. Ginseng is a natural product with worldwide distribution, and in addition to its antitumor properties, ginseng appears to be a promising radioprotector for therapeutic or preventive protocols capable of attenuating the deleterious effects of radiation on human normal tissue, especially for cancer patients undergoing radiotherapy.
Topics: Animals; Antioxidants; Drugs, Chinese Herbal; Free Radical Scavengers; Humans; Immunologic Factors; Panax; Plant Extracts; Radiation-Protective Agents; Sapogenins
PubMed: 15956041
DOI: 10.1093/mutage/gei041 -
Free Radical Research Sep 2012Molecular hydrogen (dihydrogen, H(2)) acts as a therapeutic antioxidant by selectively reducing hydroxyl radicals (•OH) and peroxynitrite (ONOO-). It has been... (Review)
Review
Molecular hydrogen (dihydrogen, H(2)) acts as a therapeutic antioxidant by selectively reducing hydroxyl radicals (•OH) and peroxynitrite (ONOO-). It has been well-known that ionising radiation (IR) causes oxidative damage and consequent apoptosis mainly due to the production of •OH that follows radiolysis of H(2)O. Our department reported the protective effect of H(2) in irradiated cells and mice for the first time, and this effect is well repeated by us and another laboratory in different experimental animal models. A randomised, placebo-controlled investigation also showed consumption of H(2) can improve the quality of life of patients treated with radiotherapy for liver tumours. These encouraging results suggested that H(2) has a potential as a radioprotective agent with efficacy and non-toxicity.
Topics: Animals; Apoptosis; Humans; Hydrogen; Hydroxyl Radical; Liver Neoplasms; Peroxynitrous Acid; Radiation-Protective Agents
PubMed: 22537465
DOI: 10.3109/10715762.2012.689429 -
Journal of Radiation Research Sep 2004In the present work, an attempt has been made to evaluate the possible in vivo radioprotection by eugenol. Swiss albino mice were administered different doses of eugenol...
In the present work, an attempt has been made to evaluate the possible in vivo radioprotection by eugenol. Swiss albino mice were administered different doses of eugenol (75,150 and 300 mg/kg) before exposure to 1.5 Gy of gamma radiation. The micronucleus test was carried out to determine the genetic damage in bone marrow. Our results demonstrated significant reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) with all three eugenol doses. Eugenol (150 mg/kg) was also tested against different doses of radiation (0.5, 1, 1.5, and 2 Gy) and was found to afford significant radioprotection. Reduction in the incidence of MnPCEs could be noticed up to 72 h postirradiation (1.5 Gy). Moreover, the level of peroxidative damage and the specific activities of lactate dehydrogenase (LDH) and methylglyoxalase I (Gly I) were observed in the liver of mice treated with eugenol for seven days in comparison to untreated mice. The results revealed that eugenol exerted significant protection against oxidative stress. This possibility was further supported by the enhanced response of Gly I and the lowered activity of LDH. The present findings suggested that eugenol has a radioprotective potential.
Topics: Animals; Bone Marrow; Dose-Response Relationship, Drug; Eugenol; Gamma Rays; Genes; Male; Mice; Micronucleus Tests; Radiation Injuries, Experimental; Radiation-Protective Agents
PubMed: 15613789
DOI: 10.1269/jrr.45.435 -
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing... Mar 2023Irradiation injuries anti-agents refer to drugs that can inhibit the initial stage of radiation injuries, or reduce the development of radiation injuries and promote the... (Review)
Review
Irradiation injuries anti-agents refer to drugs that can inhibit the initial stage of radiation injuries, or reduce the development of radiation injuries and promote the recovery of injuries when used early after irradiation exposure. According to the mechanism of action and the time of intervention, the irradiation injuries anti-agents are divided into four categories: radioprotectors, radiomitigators, radiation therapeutics for external radiation exposure, and anti-agents for internalized radionuclides. In this paper, the research progress of irradiation injuries anti-agents in recent years is reviewed.
Topics: Humans; Radiation-Protective Agents; Radiation Injuries
PubMed: 37006154
DOI: 10.3760/cma.j.cn121094-20210813-00396 -
International Journal of Pharmaceutics Apr 2020Fucoidan, a sulphated polysaccharide, plays a vital role in reducing cellular oxidative damage by exerting potential antioxidant activity. However, because of the...
Fucoidan, a sulphated polysaccharide, plays a vital role in reducing cellular oxidative damage by exerting potential antioxidant activity. However, because of the negative surface charges of oligofucoidan, it shows poor oral intestinal absorption. To overcome this drawback, the oligofucoidan polysaccharides self-assembled with opposite charge based polysaccharides (chitosan) to form the chitosan-fucoidan polysaccharides (C-FP) nanoparticles (NPs) of 190-230 nm in size. The oligofucoidan and C-FP NPs were studied for their radioprotective property using mice exposed to 5 Gy radiation. The C-FP NPs prevents radiation induced lipid peroxidation and restores intestinal enzymatic and non-enzymatic antioxidants (p < 0.05) status. In addition, hematoxylin-eosin staining revealed the radioprotective effect of oligofucoidan and C-FP NPs by mitigating the loss of crypt and villi in the small intestine. Thus, the present study demonstrated that C-FP NPs can be considered as a radioprotective agent that can be used for the prevention and treatment of Gy-radiation-induced intestine injury.
Topics: Animals; Antioxidants; Cell Line; Chitosan; Drug Delivery Systems; Drug Liberation; Drug Stability; Intestinal Absorption; Intestine, Small; Lipid Peroxidation; Mice; Molecular Weight; Nanoparticles; Particle Size; Polysaccharides; Radiation-Protective Agents
PubMed: 32081800
DOI: 10.1016/j.ijpharm.2020.119161 -
International Journal of Hematology Dec 2000Amifostine (Ethyol), the first broad-spectrum cytoprotectant approved in many countries for clinical use, is an analog of cysteamine and was originally developed by the... (Review)
Review
Amifostine (Ethyol), the first broad-spectrum cytoprotectant approved in many countries for clinical use, is an analog of cysteamine and was originally developed by the U.S. Walter Reed Army Institute of Research in the 1950s as a radioprotective agent. Studies have shown that amifostine selectively protects normal tissues of various organs from the effects of radiation and multiple cytotoxic chemotherapeutic drugs. Amifostine has demonstrated broad-spectrum cytoprotection against myelotoxicity, nephrotoxicity, xerostomia, and mucositis associated with various chemotherapy and radiation modalities. Amifostine has been evaluated in large comparative clinical trials in patients with advanced ovarian cancer, rectal cancer, and head and neck cancer, and in many phase 2 trials in patients with various neoplastic diseases. These trials have shown that amifostine delivers protection from the cytotoxic effects of cisplatin, cyclophosphamide, and radiation on various organs. Pretreatment with amifostine has also improved salivary gland tolerance of high-dose radioiodine treatment. Recent unique observations include improvement in cytopenia in patients with myelodysplastic syndrome. This review summarizes preclinical and clinical data on amifostine and includes trials that evaluated the drug's chemoprotective and radioprotective effects and other potential uses in clinical oncology.
Topics: Amifostine; Animals; Antineoplastic Agents; Clinical Trials as Topic; Cytoprotection; Humans; Neoplasms; Radiation-Protective Agents
PubMed: 11197208
DOI: No ID Found -
Redox Report : Communications in Free... 2003Amifostine (2-[(3-aminopropyl)amino]ethane-thiol dihydrogen phosphate ester; WR-2721) is a radioprotective agent used clinically to minimize damage from radiation...
Amifostine (2-[(3-aminopropyl)amino]ethane-thiol dihydrogen phosphate ester; WR-2721) is a radioprotective agent used clinically to minimize damage from radiation therapy to adjacent normal tissues. This inorganic thiophosphate requires dephosphorylation to produce the active, cell-permeant thiol metabolite, WR-1065. The activation step is presumably catalyzed by membrane-bound alkaline phosphatase, activity of which is substantially higher in the endothelium of normal tissues. This site-specific delivery may explain the preferential protection of normal versus neoplastic tissues. Although it was developed several decades ago, the mechanisms through which this agent exerts its protective effects remain unknown. Because WR-1065 is a weak base (pKa = 9.2), we hypothesized that the drug should preferentially accumulate (via proton trapping) within the acidic environment of intracellular lysosomes. These organelles contain abundant 'loose' iron and represent a likely initial target for oxidant- and radiation-mediated damage. We further hypothesized that, within the lysosomal compartment, the thiol groups of WR-1065 would interact with this iron, thereby minimizing iron-catalyzed lysosomal damage and ensuing cell death. A similar mechanism of protection via intralysosomal iron chelation has been invoked for the hexadentate iron chelator, desferrioxamine (DFO; although DFO enters the lysosomal compartment by endocytosis, not proton trapping). Using cultured J774 cells as a model system, we found substantial accumulation of WR-1065 within intracellular granules as revealed by reaction with the thiol-binding fluorochrome, BODIPY FL L-cystine. These granules are lysosomes as indicated by co-localization of BODIPY staining with LysoTracker Red. Compared to 1 mM DFO, cells pre-treated with 0.4 microM WR-1065 are protected from hydrogen peroxide-mediated lysosomal rupture and ensuing cell death. On a molar basis in this experimental system, WR-1065 is approximately 2500 times more effective than DFO in preventing oxidant-induced lysosomal rupture and cell death. This increased effectiveness is most likely due to the preferential concentration of this weak base within the acidic lysosomal apparatus. By electron spin resonance, we found that the generation of hydroxyl radical, which normally occurs following addition of hydrogen peroxide to J774 cells, is totally blocked by pretreatment with either WR-1065 or DFO. These findings suggest a single and plausible explanation for the radioprotective effects of amifostine and may provide a basis for the design of even more effective radio- and chemoprotective drugs.
Topics: Amifostine; Animals; Apoptosis; Caspases; Cell Line; Cell Membrane; DNA; Electron Spin Resonance Spectroscopy; Endocytosis; Enzyme Activation; Hydrogen Peroxide; Hydrogen-Ion Concentration; Iron; Lysosomes; Mercaptoethylamines; Mice; Models, Biological; Models, Chemical; Oxidants; Phosphates; Phosphorylation; Protons; Radiation-Protective Agents; Sulfhydryl Compounds
PubMed: 14980067
DOI: 10.1179/135100003225003384