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PURPOSE To describe the contribution of Margarita Malakyan to the development of radiation biology in Armenia and how her multidisciplinary collaboration with chemists, physicists and biologists around the world led to the development of radioprotectors and radiosensitizers of different origins. CONCLUSION Margarita Malakyan was a very active and initiative woman, a radiobiologist, whose hard work and enthusiasm led to the establishment of a very constructive scientific network and to the development of newly synthesized metal compounds. During her short but very productive life, the synthesis, characterization, as well as toxicity and radioprotective studies of different compounds led to the suggestion of a number of metal complexes of Schiff bases as effective radioprotective agents and radiosensitizers.

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.

Radioprotection is the process whereby biological systems are aided against undesirable radiation hazards. Primitive radioprotectors suffered from either having crucial side effects or low efficacy in clinical applications. Therefore, the search for less toxic but more capable radioprotectants has continued for decades. Peptides have been investigated as radioprotectants in a variety of preclinical models both in vitro and in vivo. Peptides exert their influence through scavenging free radicals, modifying cell signaling and inhibiting cell apoptosis. Demonstrating potential in vivo properties, peptide radiation countermeasures might find enough credit for use in humans in the future. This article reviews the potential therapeutic value of currently known radioprotective peptides and attempts to provide a comprehensive source for further scientific research in this area.

With the rapid application of nuclear energy and radiological technology in national economy and military field, the risk of nuclear accidents increases as well. Exposure to irradiation causes severe damages to the human body, and radioprotective agents are required for medical protection. To find the safe and effective radioprotective agents is the key for nuclear emergency. Recently, Toll like receptors (TLRs) and PHD-HIF oxygen sensing signal pathway have been extensively studied for radioprotection. Great progress has been made in this field and a number of radioprotective agents have been found. In this review, we have summarized recent findings of radioprotective roles of TLRs signaling pathway and PHD-HIF signaling pathway and discussed the general principles of developing novel radioprotective agents. These findings will provide opportunities for developing new strategies to prevent IR-induced injuries in public health events.

Cancer radiotherapy and modern synthetic medicine are critical for the treatment of cancer patients, but on the other hand they may have tremendous harmful side effect from the point of view of a weakened immune system. The focus of current research efforts in the industry and academia is not only to find affordable treatment methodologies but also to discover sources that mitigates or prevents the negative impact of these treatments on the patient’s immune system. This review will provide details of optimal methodology involving Invitro application of techniques such as phytochemical analysis, thin layer chromatography, cytogenetic analysis that were adopted to assess the efficacy of Alpinia Zerumbet extracts as a radioprotector. These methodologies provide a holistic evaluation technique for assessing any potential cytoprotective agent, especially if it’s from the herbal domain. As a case study, analytical and inferential results summary of the research conducted to assess radioprotective property of Alpinia Zerumbet, a herbal and readily available derivative, will be presented. The key findings from the research indicate that the Alpinia Zerumbet extract has potential to be an effective radioprotector, with minimal side effects as compared to synthetic chemical cytoprotective agents. Keywords: Radioprotection; cancer; herbal; Alpinia Zerumbet

Background:Radiotherapy is one of the treatment methods for cancers using ionizing radiations. About 70% of cancer patients undergo radiotherapy. Radiation effect on the skin is one of the main complications of radiotherapy and dose limiting factor. To ameliorate this complication, we used melatonin as a radioprotective agent due to its antioxidant and anti-inflammatory effects, free radical scavenging, improving overall survival after irradiation as well as minimizing the degree of DNA damage and frequency of chromosomal abrasions.Methods:Sixty male Wistar rats were randomly assigned to 4 groups: control (C), melatonin (M), radiation (R) and melatonin + radiation (MR). A single dose of 30 Gy gamma radiation was exposed to the right hind legs of the rats while 40 mg/ml of melatonin was administered 30 minutes before irradiation and 2 mg/ml once daily in the afternoon for one month till the date of rat’s sacrifice. Five rats from each group were sacrificed 4, 12 and 20 weeks after irradiation. Afterwards, their exposed skin tissues were examined histologically and biochemically.Results:In biochemical analysis, we found that malondialdehyde (MDA) levels significantly increased in R group and decreased significantly in M and MR groups after 4, 12, and 20 weeks, whereas catalase (CAT) and superoxide dismutase (SOD) activities decreased in the R group and increased in M and MR groups during the same time periods compared with the C group (p0.05) at 4 and 20 weeks except for inflammation and hair follicle atrophy, while there were significant effects at 12 weeks (pConclusion:Melatonin can be successfully used for the prevention and treatment of radiation-induced skin injury. We recommend the use of melatonin in optimal and safe doses. These doses should be administered over a long period of time for effective radioprotection and amelioration of skin damages as well as improving the therapeutic ratio of radiotherapy.

Cancer stands as one of the most common causes for death of the individual worldwide. Radiotherapy is one of the treatment modalities in cancer where, exposure of the normal tissue to these ionizing radiations, results in mutagenesis and cell death. Several modalities and clinical approaches have been made to reduce these early and late complications of the radiotherapies and one among them is, by the means of pharmacological agents. Many experimental and clinical studies have given rise to new concepts of chemical and molecular pharmacological agents as Radioprotective agents. These have been used to prevent damage to the tissues from the radiations that have been produced while diagnostic and treatment phases of carcinomas. To reduce the significant complications in irradiated patients, the clinical implication of these radioprotective agents have emerged as potential drugs and with anti-tumour effect in the radiotherapy of various cancers including oral carcinomas.

BackgroundPrevious analysis of the study (NCT02577393) had demonstrated the application of epigallocatechin-3-gallate (EGCG) could be safe and effective in the prevention and treatment of acute radiation esophagitis in patients with advanced lung cancer. EGCG seemed to improve the response rate of small cell lung cancer (SCLC) to radiotherapy in a subgroup analysis. This research continued to analyze the impact of EGCG application on cancer-radiation efficacy and patient survival.MethodsAll patients with SCLC in the NCT02577393 study were included. Patients were randomized into EGCG group or conventional therapy group as protocol. The primary endpoints of the study were radiation response rate and progression-free survival (PFS). Overall survival (OS) and the efficacy of EGCG in the treatment of esophagitis were assessed as secondary endpoints.ResultsA total of 83 patients with lung cancer in the NCT02577393 study were screened, and all 38 patients with SCLC were eligible for analysis. No significant differences with regard to baseline demographic and clinical characteristics were observed between the two groups. The objective response rate (ORR) was higher than that of conventionally treated patients (84.6 vs 50%, P = 0.045), while the median PFS and OS were not significantly prolonged. At data cut-off (1 January 2021), 5-year PFS was 33% with EGCG versus 9.3% with conventional treatment, and 5-year OS was 30.3% versus 33.3%, respectively. The mean adjusted esophagitis index and pain index of patients with EGCG application were lower than conventional treatment (5.15 ± 2.75 vs 7.17 ± 1.99, P = 0.030; 8.62 ± 5.04 vs 15.42 ± 5.04, P < 0.001).ConclusionThe study indicates EGCG may alleviate some esophagitis-related indexes in SCLC patients exposed to ionizing radiation without reducing survival. However, this conclusion should be confirmed by further studies with large sample size.

There are various radioprotective agents with different mechanisms that help to decrease ionizing radiation side effects. The radioprotective effect of Cimetidine and IMOD was assessed individually and compared with the hybrid radioprotectors agents (HRPAs-IMOD and Cimetidine) on human lymphocyte cells.Twenty healthy volunteers (ten men and ten women) participated in the present study. About 75 mL peripheral blood lymphocytes from each individual were collected, and they were divided into 36 groups. Briefly, the blood samples were treated with different concentrations of Cimetidine (12.6 and 25.2 μg/mL) and IMOD (0.04, 0.08, and 0.12 mg/mL), and also a combination of these agents, namely hybrid radioprotectors agents (HRPAs). Besides, the irradiated groups were exposed to 2 and 4 Gy of Co-60 gamma irradiation. The amount of cellular damage was assessed using the micronucleus assay. The repeated measurements and paired T-test statistical analysis were used to compare the micronucleus frequencies in different groups.The micronucleus frequencies were significantly reduced (p 0.05) in irradiated groups when the non-toxic concentrations of Cimetidine, IMOD, and HRPAs have been used. The reduction in micronucleus frequency was obtained 5-29% for Cimetidine and 40-51% for IMOD in peripheral blood lymphocytes irradiated with 2 Gy. This reduction in 4 Gy irradiation was 8-17% for Cimetidine and 27-37% for IMOD. The HRPAs resulted in a higher radioprotective effect, in a way that they cause up to 58% and 43% micronucleus frequency reduction in 2 and 4 Gy, respectively.In conclusion, the HRPAs showed the highest level of radioprotective. In addition, IMOD was remarkably higher radioprotective than Cimetidine, which may be related to its greater non-toxic concentrations.

Abstract: Ionising radiation has been an important modality in cancer treatment and its value is immense when surgical intervention is risky or might debilitate/adversely affect the patient. However, the beneficial effect of radiation modality is negated by the damage to the adjacent healthy tissue in the field of radiation. Under these situations, the use of radioprotective compounds that can selectively protect normal tissues against radiation injury is considered very useful. However, research spanning over half a century has shown that there are no ideal radioprotectors available. The United States Food and Drug Administration (FDA or USFDA) approved amifostine, or WR-2721 (Walter Reed-2721) [chemically S-2-(3-aminopropyl-amino) ethyl phosphorothioic acid] is toxic at their optimal concentrations. This has necessitated the need for agents that are safe and easily acceptable to humans. Background: Dietary agents with beneficial effects like free radical scavenging, antioxidant and immunomodulatory effects are being recognized as useful and have been investigated for their radioprotective properties. Studies in these lines have shown that the fruits of Aegle marmelos (stone apple or bael), Emblica officinalis or Phyllanthus emblica (Indian gooseberry/amla), Eugenia jambolana or Syzygium jambolana (black plum/jamun), Mangifera indica (mango) and Grewia asiatica (phalsa or falsa) that are originally reported to be indigenous to India have been investigated for their usefulness as radioprotective agents. Objective: The objective of this review is to summarize the beneficial effects of the Indian indigenous fruits, stone apple, mango, Indian gooseberry, black plum, and phalsa, in mitigating radiation-induced side effects, emphasize the underlying mechanism of action for the beneficial effects and address aspects that merit detail investigations for these fruits to move towards clinical application in the near future. Methods: The authors data-mined Google Scholar, PubMed, Embase, and the Cochrane Library for publications in the field from 1981 up to July 2020. The focus was on the radioprotection and the mechanism responsible for the beneficial effects, and accordingly, the articles were collated and analyzed. Results: This article emphasizes the usefulness of stone apple, mango, Indian gooseberry, black plum, and phalsa as radioprotective agents. From a mechanistic view, reports are suggestive that the beneficial effects are mediated by triggering free radical scavenging, antioxidant, anti-mutagenic and anti-inflammatory effects. Conclusion: For the first time, this review addresses the beneficial effects of mango, Indian gooseberry, black plum, stone apple and phalsa as radioprotective agents. The authors suggest that future studies should be directed at understanding the selective radioprotective effects with tumor-bearing laboratory animals to understand their usefulness as radioprotective drug/s during radiotherapy and as a food supplement to protect people from getting exposed to low doses of radiation in occupational settings. Phase I clinical trial studies are also required to ascertain the optimal dose and the schedule to be followed with the standardized extract of these fruits. The most important aspect is that these fruits, being a part of the diet, have been consumed since the beginning of mankind, are non-toxic, possess diverse medicinal properties, have easy acceptability, all of which will help take research forward and be of benefit to patients, occupational workers, agro-based sectors and pharma industries.

Radiation therapy plays a critical role in the management of a wide range of hematologic malignancies. It is well known that the post-irradiation damages both in the bone marrow and in other organs are the main causes of post-irradiation morbidity and mortality. Tumor control without producing extensive damage to the surrounding normal cells, through the use of radioprotectors, is of special clinical relevance in radiotherapy. An increasing amount of data is helping to clarify the role of oxidative stress in toxicity and therapy response. Radioprotective agents are substances that moderate the oxidative effects of radiation on healthy normal tissues while preserving the sensitivity to radiation damage in tumor cells. As well as the substances capable of carrying out a protective action against the oxidative damage caused by radiotherapy, other substances have been identified as possible enhancers of the radiotherapy and cytotoxic activity via an oxidative effect. The purpose of this review was to examine the data in the literature on the possible use of old and new substances to increase the efficacy of radiation treatment in hematological diseases and to reduce the harmful effects of the treatment.

Objective: To reduce the chances of toxicity, reduction in radiation dose or reducing the frequency of the therapy is done which usually leads to a therapeutically poor outcome. The most feasible method is to protect the normal cells by administration of radioprotective agents either before or after the exposure. These agents have been tested on animals and human cellmodels for evaluating theirsafety window and toxicityprofile at the cellular level. The study aims to compile the effective natural radioprotective agents available which can be further exploited by using certain QSAR studies to increase their potency. Method: Structured literature search from EMBASE, PubMed, Bentham Science, Scopus, and ScienceDirect was done and appropriate peer-reviewed review articles, as well as certain research articles, were included and compiled in this review paper. Conclusion: As various studies have indicated the harmful effects of ionizing radiations on normal cells, to reduce these effects radioprotective agents are used before or after exposure to radiations. Compounds derived from natural sources are proved to have few side effects and they possess radioprotective property due to the presence of alkaloids, resins, volatile oils, tannins in their molecular structure. Various plants having such radioprotective constitutes have been identified for their radioprotective action and compiled in the present study. Conclusion: As various studies have indicated the harmful effects of ionizing radiations on normal cells, to reduce these effects radioprotective agents are used before or after exposure to radiations. Compounds derived from natural sources are proved to have few side effects and they possess radioprotective property due to the presence of alkaloids, resins, volatile oils, tannins in their molecular structure. Various plants having such radioprotective constitutes have been identified for their radioprotective action and compiled in the present study.

Historically, patients with localized soft tissue sarcomas (STS) of the extremities would undergo limb amputation. It was subsequently determined that the addition of radiation therapy (RT) delivered prior to (neoadjuvant) or after (adjuvant) a limb-sparing surgical resection yielded equivalent survival outcomes to amputation in appropriate patients. Generally, neoadjuvant radiation offers decreased volume and dose of high-intensity radiation to normal tissue and increased chance of achieving negative surgical margins—but also increases wound healing complications when compared to adjuvant radiotherapy. This review elaborates on the current neoadjuvant/adjuvant RT approaches, wound healing complications in STS, and the potential application of novel radioprotective agents to minimize radiation-induced normal tissue toxicity.

Radiation-induced endothelial/vascular injury is a major complicating factor in radiotherapy and a leading cause of morbidity and mortality in nuclear or radiological catastrophes. Exposure of tissue to ionizing radiation (IR) leads to the release of oxygen radicals and proteases that result in loss of endothelial barrier function and leukocyte dysfunction leading to tissue injury and organ damage. Microvascular endothelial cells are particularly sensitive to IR and radiation-induced alterations in endothelial cell function are thought to be a critical factor in organ damage through endothelial cell activation, enhanced leukocyte-endothelial cell interactions, increased barrier permeability and initiation of apoptotic pathways. These radiation-induced inflammatory responses are important in early and late radiation pathologies in various organs. A better understanding of mechanisms of radiation-induced endothelium dysfunction is therefore vital, as radiobiological response of endothelium is of major importance for medical management and therapeutic development for radiation injuries. In this review, we summarize the current knowledge of cellular and molecular mechanisms of radiation-induced endothelium damage and their impact on early and late radiation injury. Furthermore, we review established and emerging in vivo and in vitro models that have been developed to study the mechanisms of radiation-induced endothelium damage and to design, develop and rapidly screen therapeutics for treatment of radiation-induced vascular damage. Currently there are no specific therapeutics available to protect against radiation-induced loss of endothelial barrier function, leukocyte dysfunction and resulting organ damage. Developing therapeutics to prevent endothelium dysfunction and normal tissue damage during radiotherapy can serve as the urgently needed medical countermeasures.

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.

This review summarizes recent progress in understanding the role of p53-upregulated mediator of apoptosis (PUMA) in molecular pathways with respect to its potential therapeutic applications. Particular emphasis is given to the PUMA´s role in ionizing radiation-induced signalling as radiotoxicity of normal tissue is mediated mostly via apoptosis. PUMA and its p53-dependent and p53- independent induction are described and potential use as a new target for the development of radioprotective agents is suggested. Further implications, including targeting PUMA to prevent and treat cardiovascular and neurodegenerative diseases, are also discussed together with an overview of other therapeutic applications. Finally, basic chemical structures for the development of novel PUMA modulators such as pifithrine derivatives, kinase inhibitors or modulators of Bcl-2 protein family are described.

Radiotherapy for cancer patients damages normal tissues, thereby inducing an inflammatory response and promoting cancer metastasis. We investigated whether nicaraven, a compound with radioprotective and anti-inflammatory properties, could attenuate radiation-induced cancer metastasis to the lungs of mice. Nicaraven and amifostine, another commercial radioprotective agent, had limited effects on both the radiosensitivity of Lewis lung carcinoma cells in vitro and radiation-induced tumor growth inhibition in vivo. Using experimental and spontaneous metastasis models, we confirmed that thorax irradiation with 5 Gy X-rays dramatically increased the number of tumors in the lungs. Interestingly, the number of tumors in the lungs was significantly reduced by administering nicaraven but not by administering amifostine daily after radiation exposure. Furthermore, nicaraven administration effectively inhibited CCL8 expression and macrophage recruitment in the lungs 1 day after thorax irradiation. Our data suggest that nicaraven attenuates radiation-induced lung metastasis, likely by regulating the inflammatory response after radiation exposure., Cancer Letters, 418, pp.204-210; 2018

Zirconium-89 is currently being used in numerous clinical trials involving monoclonal antibodies and positron emission tomography. This report describes a revised strategy that reduces preparation time while increasing the specific activity of clinically relevant immuno-PET agents. Additionally, it demonstrates that n-acetyl-L-cysteine acts as a superior radioprotective agent that improves long-term stability without compromising antigen affinity in vivo.

Protection of normal tissues against ionizing radiation-induced damages is a critical issue in clinical and environmental radiobiology. One of the ways of accomplishing radiation protection is through the use of radioprotectors. In the search for the most effective radioprotective agent, factors such as toxicity, effect on tumors, number of tissues protected, ease of administration, long-term stability, and compatibility with other drugs need to be assessed. Thus, in the present study, we systematically review existing studies on a chemical radioprotector, Ex-RAD, with the aim of examining its efficacy of radiation protection as well as underlying mechanisms. To this end, a systematic search of the electronic databases including Pubmed, Scopus, Embase, and Google Scholar was conducted to retrieve articles investigating the radioprotective effect of Ex-RAD. From an initial search of 268 articles, and after removal of duplicates as well as applying the predetermined inclusion and exclusion criteria, 10 articles were finally included for this systematic review. Findings from the reviewed studies indicated that Ex-RAD showed potentials for effective radioprotection of the studied organs with no side effect. Furthermore, the inhibition of apoptosis through p53 signaling pathway was the main mechanism of radioprotection by Ex-RAD. However, its radioprotective effect would need to be investigated for more organs in future studies.

Considering the remarkable application of radiotherapy in the treatment and diagnosis of various diseases and even nuclear war, it is important to protect healthy tissues and people at risk from the radiation. Currently, there is no ideal and safe radioprotective agent available and we are seeing a great effort to find these agents from natural sources. Phenolic compounds, as well as flavonoid, are presented widely as the second metabolite in plants and they have been considered for investigation according to their benefits for human health, healing and preventing many disorders. The major bioactive benefits of flavonoids include antioxidant, anti-inflammatory, anti-tumor, anti-aging, anti-bacterial and viral, neuroprotection and radioprotective effects. Their lower toxicity and oral administration have made it suitable for radiotherapy patient, radiation, military forces, and even the general public. This review attempts to provide a summary of the main molecular mechanisms involved in flavonoid radio-protective effects. Data of these studies will provide a comprehensive perspective to flavonoids and can help to optimize their effects in radioprotection procedures.

Background and objectives: Ionizing radiation (IR) has been of immense benefit to man, especially for medical purposes (diagnostic imaging and radiotherapy). However, the risks of toxicity in healthy normal cells, leading to cellular damage as well as early and late side effects, have been major drawbacks. The aim of this study was to evaluate the radioprotective effect of hesperidin against IR-induced damage. Materials and Methods: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were applied in reporting this study. A search was conducted using the electronic databases PubMed, Scopus, Embase, Google Scholar, and www.ClinicalTrials.gov for information about completed or ongoing clinical trials. Results: From our search results, 24 studies involving rats, mice, and cultured human and animal cells were included. An experimental case—control design was used in all studies. The studies showed that the administration of hesperidin reduced oxidative stress and inflammation in all investigated tissues. Furthermore, it increased 30-day and 60-day survival rates and protected against DNA damage. The best radioprotection was obtained when hesperidin was administered before irradiation. Conclusions: The results of the included studies support the antioxidant, anti-inflammatory, and antiapoptotic abilities of hesperidin as a potential radioprotective agent against IR-induced damage. We recommend future clinical trials for more insights.

The purpose of this study was to test the radioprotective effect of selenium in the bone microarchitecture of irradiated rats mandibles. Forty rats were separated into 4 groups with 10 animals: control group (CG), irradiated group (IG), sodium selenite group (SSG) and sodium selenite irradiated group (SSIG). A single dose of 0.8 mg/kg sodium selenite was administered intraperitoneally in the SSG and SSIG groups. One hour later, animals of IG and SSIG groups were irradiated with 15 Gy of x-rays. Forty days after radiation a bilateral extraction of the mandibular first molars was performed. After the extraction procedure, five rats were killed after fifteen days and others five after thirty days. Micro- computed tomography was used to evaluate cortical and trabecular bone of each rat. The mean and standard deviation of each bone microarchitecture parameter were analyzed using the statistical test of two-way Analysis of Variance (ANOVA). At 15 days, the bone volume presented higher values in the CG and SSG groups (p=0.001). The same groups presented statistically significant higher values when bone volume fraction (p

Background: Drugs are being sought that are effective as radioprotection for use in both planned and unplanned radiation exposure. Traditional Chinese medicines have been used successfully for the treatment of free radical-mediated diseases and therefore we expected that exploring such agents could yield an effective radioprotector. We therefore evaluated the radioprotective effects of 13 traditional Chinese medicine compounds (TCMCs) against ionizing radiation damage. Materials and methods: TCMCs were tested in vitro on human kidney 293T cells treated with 0, 2, 4, 6, 8 or 10 Gy irradiation for their ability to promote cell survival. Mice were subjected to a sub-lethal (4 Gy), lethal (7 Gy) or supra-lethal (13 Gy) dose of total-body irradiation (TBI) and TCMCs were tested for their ability to influence survival and hemopoietic function. Results: Of the 13 TCMCs tested, five including bupleurum, shenmai, and breviscapine, promoted survival of 293T cells. bupleurum, shenmai, and breviscapine also prolonged survival times of mice treated with supra-lethal and lethal TBI doses. As expected of an effective radioprotector, they also ameliorated bone marrow suppression, reducing the decrease in bone marrow cells after sub-lethal TBI, and they attenuated the TBI-induced reduction in granulocyte-macrophage colony-forming units. Conclusion: This investigation of TCMCs in vitro and in vivo identified bupleurum, shenmai, and breviscapine as having characteristics consistent with radioprotective agents. Further investigation to identify the bioactive components responsible for the radioprotective effect of these compounds is now required.

Radioprotective agents are substances those reduce the effects of radiation in healthy tissues while maintaining the sensitivity to radiation damage in tumor cells. Due to increased awareness about radioactive substances and their fatal effects on human health, radioprotective agents are now the topic of vivid research. Scavenging of free radicals is the most common mechanism in oncogenesis that plays an important role in protecting tissues from lethal effect of radiation exposure therefore radioprotectors are also good anti-cancer agents. There are numerous studies indicating plant-based therapeutics against cancer and radioprotection. Such plants could be further explored for developing them as promising natural radioprotectors with anti-cancer properties. This review systematically presents information on plants having radioprotective and anti-cancer properties.

Ionizing radiation (IR) targeted at killing cancer cells also damages normal human cells and tissues through oxidative stress. Thus, the practical treatment of cancer using radiation therapy (RT) is sometimes limited because of the acute side effects in individual patients. In addition, some radioresistant cancers are difficult to treat with limited doses of IR, which leads to treatment failure. Natural chemicals that have unique physiological functions and low toxicity offer significant advantages for the development of new radiation therapies. Natural chemicals can counteract the oxidative damage caused by IR during RT because of their strong antioxidant ability. Certain natural chemicals can also serve as radiosensitizers that can enhance the cancer-killing effects. This review article discusses the main roles of radio-functional natural chemicals in the development of cancer RT.

Radiation countermeasures are radioprotective agents that reduce the harmful effects of ionizing radiation. They have wide range of applications extending from protection of normal tissues of cancer patients during radiotherapy to safeguard people aftermath of radiologic or nuclear accidents. Despite the screening of thousands of natural and synthetic compounds, only few found place in clinic with limited tolerance. Therefore, mechanistic understanding is essential in the development of more suitable and customized radiation countermeasure agents. This review focuses on the mechanisms of radioprotection imparted by these agents. Radioprotectors are diverse and act through widely varying mechanisms that can be classified in 10 categories: 1) scavenging of free radicals; 2) enhancing DNA repair; 3) synchronizing of cells; 4) modulating redox sensitive genes; 5) modulating growth factors and cytokines; 6) inhibiting apoptosis; 7) repurposing of drug; 8) interacting and chelating of radionuclides; and therapeutic methods of tissue regeneration such as 9) gene therapy; and 10) stem cell therapy. The most common mechanism of radioprotection is the scavenging of free radicals whereas, modulation of growth factors, cytokines and redox genes emerge as effective strategies. Gene and stem cell therapies as therapeutic radiation countermeasures are being developed and can be applied in the near future to minimize the side effects of radiation exposure through tissues regenerations. Thus, the management of radiation exposure may require a holistic multi-mechanistic approaches to achieve optimal radiation protection during radiotherapy of cancer patients and in cases of nuclear eventualities.

Medical imaging has become a central component of patient care to ensure early and accurate diagnosis. Unfortunately, many imaging modalities use ionizing radiation to generate images. Ionizing radiation even in low doses can cause direct DNA damage and generate reactive oxygen species and free radicals, leading to DNA, protein, and lipid membrane damage. This cell damage can lead to apoptosis, necrosis, teratogenesis, or carcinogenesis. As many as 2% of cancers (and an associated 15,000 deaths annually) can be linked to computed tomography exposure alone. Radioprotective agents have been investigated using various models including cells, animals, and recently humans. The data suggest that radioprotective agents working through a variety of mechanisms have the potential to decrease free radical damage produced by ionizing radiation. Radioprotective agents may be useful as an adjunct to medical imaging to reduced patient morbidity and mortality due to ionizing radiation exposure. Some radioprotective agents can be found in high quantities in antioxidant rich foods, suggesting that a specific diet recommendation could be beneficial in radioprotection.

While radiotherapy continues to be a major cancer treatment option, its dose-limiting side effects, such as pulmonary fibrosis, severely impair the quality of life in these patients. In this study, we evaluated the radioprotective effects of metformin, a commonly used biguanide antidiabetic medication, in a murine model of pulmonary damage. Sprague Dawley® rats received whole lung 20 Gy irradiation with or without metformin treatment. Computed tomography (CT) was performed and Hounsfield units (HU) were determined during the observation period. Histological analysis and evaluation of fibrosis/inflammatory markers by Western blot were performed at 12 weeks postirradiation. CCK-8 and colony formation assays were used to explore the effects of metformin on non-small cell lung cancer cells A549 and H460. Results of this study showed that metformin reduced radiological and histological signs of fibrosis, inflammatory infiltration, alterations to alveolar structures and radiation-induced HU lung density. In addition, metformin was found to significantly decrease collagen 1a and TGF-β expression and inhibit p-Smad2 and p-Smad3 expression compared to that of the irradiated group alone. Moreover, metformin reduced A549 and H460 cell growth and clonogenic survival. In conclusion, metformin exerted a protective effect on normal tissues from radiation-induced pulmonary injury, and shows promise as a radioprotective agent in the treatment of lung cancer.

We studied radioprotective effects of a preparation based on yeast RNA and its influence on therapeutic efficiency of ionizing radiation against transplanted tumors. Parenteral administration of yeast RNA preparation to mice in a dose of 10 mg 1 h prior to exposure to ionizing γ-radiation (137Cs) in a lethal dose (LD80/30) increased 30-day survival by 66%; by day 80, 80% of animals survived (vs. 2.5% in the control). Whole-body exposure to ionizing γ-radiation in a dose of 7 Gy significantly increased the mean lifespan of mice with experimental lung metastases or intraperitoneally transplanted leukemia L-1210 by 42 and 20.8%, respectively. RNA preparation injected to the mice with tumors 1 h before irradiation did not affect the therapeutic efficiency of ionizing radiation or significantly potentiated it (in mice with transplanted leukemia L-1210). These results suggest that yeast RNA preparation protects healthy tissues during radiotherapy of malignant tumors.

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.

INTRODUCTION: Radioprotective agents are of interest for application in radiotherapy for cancer and in public health medicine in the context of accidental radiation exposure. Methylproamine is the lead compound of a class of radioprotectors which act as DNA binding anti-oxidants, enabling the repair of transient radiation-induced oxidative DNA lesions. This study tested methylproamine for the radioprotection of both directly targeted and bystander cells.METHODS: T98G glioma cells were treated with 15 μM methylproamine and exposed to (137)Cs γ-ray/X-ray irradiation and He(2+) microbeam irradiation. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or γH2AX assay.RESULTS: Radioprotection of directly targeted T98G cells by methylproamine was observed for (137)Cs γ-rays and X-rays but not for He(2+) charged particle irradiation. The effect of methylproamine on the bystander cell population was tested for both X-ray irradiation and He(2+) ion microbeam irradiation. The X-ray bystander experiments were carried out by medium transfer from irradiated to non-irradiated cultures and three experimental designs were tested. Radioprotection was only observed when recipient cells were pretreated with the drug prior to exposure to the conditioned medium. In microbeam bystander experiments targeted and nontargeted cells were co-cultured with continuous methylproamine treatment during irradiation and postradiation incubation; radioprotection of bystander cells was observed.DISCUSSION AND CONCLUSION: Methylproamine protected targeted cells from DNA damage caused by γ-ray or X-ray radiation but not He(2+) ion radiation. Protection of bystander cells was independent of the type of radiation which the donor population received.

There has been only modest change in cancer incidence and mortality during the past several decades, but the number of cancer survivors has almost tripled during the same period. With an increasing cohort of cancer survivors, efforts to prevent, diagnose, and manage side effects of cancer therapy in general and, specifically those of radiation therapy have intensified. Many cancer survivors have undergone radiation therapy of tumors in the pelvis or abdomen, thus rendering the bowel at risk for injury. In fact, the current prevalence of patients with long term radiation-induced intestinal side effects exceeds that of ulcerative colitis and Crohn’s disease combined. Significant progress toward reducing toxicity of radiation therapy has been made by the introduction of so-called dose-sculpting treatment techniques, which allow more precise delivery of the radiation beam. Moreover, new insight into the underlying pathophysiology have resulted in an improved understanding of mechanisms of radiation-induced bowel toxicity and in development of new diagnostic strategies and management opportunities. This article discusses the pathogenesis of early and delayed radiation-induced bowel toxicity, reviews current management options, and outlines priorities for future research. The gastroenterologist by adding insight into molecular and cellular mechanisms of related bowel disorders can substantially strengthen these efforts.

Recent studies showed that hydrogen can be used as an effective radioprotective agent through scavenging free radicals. This study was undertaken to evaluate the radioprotective effects of hydrogen on immune system in mice. H(2) was dissolved in physiological saline using an apparatus produced by our department. Spleen index and histological analysis were used to evaluate the splenic structural damage. Spleen superoxide dismutase, GSH, MDA were measured to appraise the antioxidant capacity and a DCF assay for the measurement of radical oxygen species. Cell apoptosis was evaluated by an Annexin V-FITC and propidium iodide staining method as well as the apoptotic proteins such as Bcl-2, Bax, caspase-3 and c-caspase-3. CD4+ and CD8+ T cells subtypes were detected by flow cytometry with FITC-labelled antimouse CD4 and PE antimouse CD8 staining. Real-time PCR was utilized to determine the CD4+ T cell subtypes and related cytokines. Our study demonstrated that pre-treatment with H(2) could increase the spleen index and attenuate the radiation damage on splenic structure. Radical oxygen species level was also reduced by H(2) treatment. H(2) also inhibited radiation-induced apoptosis in splenocytes and down-regulated pro-apoptotic proteins in living mice. Radiation-induced imbalance of T cells was attenuated by H(2). Finally, we found that H(2) could regulate the polarization of CD4+ T cells and the level of related cytokines. This study suggests H(2) as an effective radioprotective agent on immune system by scavenging reactive oxygen species.

Radiotherapy is regarded as one of the most important therapeutic modality for the treatment of malignant lesions. This field is undergoing rapid advancements in the recent times. With the use of radiosensitizers and radioprotective agents, the course of radiotherapy has improved the sensitization of tumor cells and protection of normal cells, respectively. The aim of this paper was to critically review and analyze the available compounds used as radiosensitizers, radioprotectors, and radiation mitigators. For reviewing, the author used the electronic search for the keywords 'Radiosensitizers', 'Radioprotectors', 'Radiation mitigators' on PubMed for inclusion of previously published articles and further search of reference papers on individual radiosensitizing and radioprotecting agents was done. Radiosensitizers are agents that sensitize the tumor cells to radiation. These compounds apparently promote fixation of the free radicals produced by radiation damage at the molecular level. The mechanism of action is similar to the oxygen effect, in which biochemical reactions in the damaged molecules prevent repair of the cellular radiation damage. Free radicals such as OH + are captured by the electron affinity of the radiosensitizers, rendering the molecules incapable of repair. Radioprotectors are compounds that are designed to reduce the damage in normal tissues caused by radiation. These compounds are often antioxidants and must be present before or at the time of radiation for effectiveness. Other agents, termed mitigators, may be used to minimize toxicity even after radiation has been delivered. This article tries to discuss the various aspects of radiosensitizers, radioprotectors, and radiation mitigators including the newer agents.

This review takes an indepth look at adaptogens (compounds that increase the body's protective resources) and related pharmacological groups of drugs: immunomodulators, actoprotectors, antihypoxants, antioxidants, radioprotective and radiosensitizer compounds. The mechanisms and biochemical characteristics of drug action of these medical substances are discussed in relation to their structure. Bibliography: 212 references.

Development of radioprotective agents has focused primarily on cytoprotection from relatively high doses of therapeutic radiation and nuclear disasters. Epidemiological studies and radiobiological models report the potential for stochastic effects from relatively low-dose radiation exposure. Diagnostic studies like computed tomography (CT) expose the patient to a small but significant amount of radiation, which has been reported to increase the risk for carcinogenesis. Young patients expected to undergo multiple CT studies may benefit from a protective agent given prior to CT. This review includes published data of agents that have been shown to protect against radiation-induced carcinogenesis. A discussion follows regarding the data that describes the extent of radiation exposure during CT, as well as technical modifications, which also reduce radiation exposure.Most experiments have used in vivo animal models or in vitro cell lines. Ethical barriers prevent large-scale human studies, although, there are two prospective human studies from the Chernobyl nuclear accident. Collectively, all of these studies provide evidence of statistically significant reductions in radiation-induced carcinogenesis. Protection is achieved by several mechanisms, which include free radical scavenging, caloric restriction, non-steroidal anti-inflammatory agents, humoral factors, and an oxidative agent. Enhanced efficacy is achieved when targeting multiple mechanisms. The data presented provides the scientific foundation for future development of a radioprotectant that may reduce the risk of carcinogenesis from low-dose exposure when certain at-risk populations undergo diagnostic studies like CT.

Objectives: Ionising radiation has deleterious effects on human cells. N-acetylcysteine (NAC) and cysteine, the active metabolite of NAC, are well-known radioprotective agents. Recently, a serine-magnesium sulfate combination was proposed as an antidote for organophosphate toxicity. This study aimed to investigate the use of a serine-magnesium sulfate mixture in the prevention of γ-radiation-induced DNA damage in human lymphocytes as compared to NAC and cysteine. Methods: This study was carried out at the Iran University of Medical Sciences, Tehran, Iran, between April and September 2016. Citrated blood samples of 7 mL each were taken from 22 healthy subjects. Each sample was divided into 1 mL aliquots , with the first aliquot acting as the control while the second was exposed to 2 Gy of γ-radiation at a dose rate of 102.7 cGy/minute. The remaining aliquots were separately incubated with 600 μM concentrations each of serine, magnesium sulfate, serine-magnesium sulfate, NAC and cysteine before being exposed to 2 Gy of γ-radiation. Lymphocytes were isolated using a separation medium and methyl-thiazole-tetrazolium and comet assays were used to evaluate cell viability and DNA damage, respectively. Results: The serine-magnesium sulfate mixture significantly increased lymphocyte viability and reduced DNA damage in comparison to serine, magnesium sulfate, NAC or cysteine alone ( P

Background Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR gamma agonist rosiglitazone is of interest in prevention and therapy of radiation-induced toxicities. We aimed to evaluate the radioprotective effect of rosiglitazone in a mouse model of radiation-induced oral mucositis. Material and methods Oral mucositis was obtained by irradiation of the oral region of C57BL/6J mice, pretreated or not with rosiglitazone. Mucositis was assessed by macroscopic scoring, histology and molecular analysis. Tumor xenograft was obtained by s.c. injection of Hep-2 cells in CD1 mice. Tumor volume was measured twice a week to evaluate effect of rosiglitazone alone and combined with radiotherapy. Results Irradiated mice showed typical features of oral mucositis, such as oedema and reddening, reaching the peak of damage after 12–15 days. Rosiglitazone markedly reduced visible signs of mucositis and significantly reduced the peak. Histological analysis showed the presence of an inflammatory cell infiltrate after irradiation; the association with rosiglitazone noticeably reduced infiltration. Rosiglitazone significantly inhibited radiation-induced tnfα, Il-6 and Il-1β gene expression. Rosiglitazone controlled the increase of TGF-β and NF-kB p65 subunit proteins induced by irradiation, and enhanced the expression of catalase. Irradiation and rosiglitazone significantly reduced tumor volume as compared to control. Rosiglitazone did not protect tumor from the therapeutic effect of radiation. Conclusion Rosiglitazone exerted a protective action on normal tissues in radiation-induced mucositis. Moreover, it showed antineoplastic properties on head-neck carcinoma xenograft model and selective protection of normal tissues. Thus, PPAR gamma agonists should be further investigated as radioprotective agents in head and neck cancer.

We investigated the effects of Phellinus linteus extracts (PLEs) against radiation damage in mice. First, BALB/c mice were irradiated once with γ-rays at 4, 5, 6, or 8 Gy and allowed to recover for 20 days. Results reveal that 8-Gy radiation caused death in 100% of mice on day 13, and 6-Gy radiation caused death in 86.7% of mice (13/15) at the end of the experiment, whereas 4- and 5-Gy radiation did not result in any death. We then used 5-Gy γ-ray radiation to examine the protective effects of PLEs. Mice were orally administered a PLE (500, 1000, and 1500 mg/kg) daily for 2 weeks before radiation and for 6 weeks after radiation. γ-Ray radiation significantly decreased body weight starting from week 2 after radiation. Supplementation with a median and high dose of PLE significantly restored body weights starting at weeks 5 and 3, respectively. The radiation-protective agent WR2721 (200 mg/kg intraperitoneally) restored body weights starting at week 4. White blood cells, platelets, red blood cells, and hemoglobin were significantly decreased by radiation, and PLEs (primarily at high doses) and WR2721 significantly prevented hematologic abnormality. These results suggest that PLE has potential as a radioprotective agent.

Exposure to ionizing radiation causes damage to living tissues; however, only a small number of agents have been approved for use in radiation injuries. Radioprotector is the primary countermeasure to radiation injury and none radioprotector has indeed reached the drug development stage. Repurposing the long list of approved, non-radioprotective drugs is an attractive strategy to find new radioprotective agents. Here, we applied a computational approach to discover new radioprotectors in silico by comparing publicly available gene expression data of ionizing radiation-treated samples from the Gene Expression Omnibus (GEO) database with gene expression signatures of more than 1309 small-molecule compounds from the Connectivity Map (cmap) dataset. Among the best compounds predicted to be therapeutic for ionizing radiation damage by this approach were some previously reported radioprotectors and baclofen (P

To study the protective effect of an extract of Guipi Pill (归脾丸) against radiationinduced damage. A total of 100 Kunming mice were randomly divided into normal group, model group, positive drug group (treated with radioprotective agent “523”, 5 mg/kg at 24 h before irradiation) and two treatment groups, with 20 mice in each group. The extract of water extraction-alcohol precipitation (WAP) from Guipi Pill were administered orally to the mice in the two treatment groups at the dose of 500 and 1,000 mg/kg, respectively, for 6 days prior to whole body radiation (8 Gy). Fifty mice with 10 in each group were used to observe the survival rate 30 days after radiation. The other 50 mice with 10 in each group were sacrificed on day 10 after radiation (6 Gy) in order to take blood, liver and unilateral femur. Pretreatment prior to irradiation with WAP resulted in a significantly higher 30-day survival rate of mice after exposure to a potentially lethal dose of 8-Gy radiation. WAP could significantly increase the total white blood cell count and DNA content of bone marrow, and it also increased the activity of various antioxidant enzymes, such as superoxide dismutase, catalase, total antioxidant capacity and glutathione peroxidase in liver tissue of mice, which were reduced by radiation treatment. Maleic dialdehyde level and bone marrow micronucleus rate were significantly reduced by WAP, which were increased after 6-Gy radiation. WAP of Guipi Pill could increase the 30-day survival rate and the antioxidant capacity as well as protect bone marrow in mice. WAP of Guipi Pill is an effective radioprotective agent.

Radiation-induced liver toxicity is a major limitation to the use of radiation in the treatment of intrahepatic cancers. The purpose of this study was to evaluate the potential radioprotective effect of a smallmolecule tumor necrosis factor alpha (TNF-) inhibitor, UTL-5g, against radiation-induced acute liver injury. Mice were pre-treated by i.p. injection with UTL-5g and control vehicle one hr prior to liver irradiation at 15 Gy. Blood and liver were collected 2 hr after irradiation and analyzed for levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in serum and TNF- in liver tissue extracts. Both AST and ALT in serum and TNF- in liver induced by irradiation were significantly reduced by UTL-5g in a drug dose-dependent manner. The reductions of AST, ALT and TNF- appeared to correlate with the reduction of liver apoptosis detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. A radiation dose escalation study (5, 15 and 25 Gy) showed that UTL-5g at 60 mg/kg was effective as a radioprotective agent at 5 and 15 Gy; the protection was only modest at 25 Gy. In summary, our results suggest that the TNF- inhibitor, UTL-5g, is potentially radioprotective against acute phase of radiation-induced liver injury.

Objectives: Preparations of herbal drugs have drawn considerable interest in scientific community in recent years for the treatment of several stress related health problems including radiation-injury. Materials and Methods: An aqueous extract from Valeriana wallichii containing hesperidin as one of its major constituent was evaluated for its ability to protect against radiation-injury in model systems like plasmid deoxyribonucleic acid (DNA) and cultured human fibroblast cells. Results: The extract was found to significantly counter radiation-induced free radicals at 4 h after 5 Gy irradiation, reduced prolonged oxidative stress led increase in mitochondrial mass, enhanced reproductive viability of cultured cells and protected against radiation-induced DNA damage in solution. Discussion: Further studies are required to validate the radioprotective ability of the extract and to develop a safer radioprotective agent.

Pharmacological effects of Panax ginseng have been demonstrated in cardiovascular system, endocrine secretion and immune system, together with antitumor, anti-stress and anti-oxidant activities. Modern scientific data show protective effect of ginseng against bone marrow cell death, increased survival rate of experimental animals, recovery of hematopoietic injury, immunopotentiation, reduction of damaged intestinal epithelial cells, inhibition of mutagenesis and effective protection against testicular damages, caused by radiation exposure. And also, ginseng acts in indirect fashion to protect radical processes by inhibition of initiation of free radical processes and thus reduces the radiation damages. The research has made much progress, but still insufficient to fully uncover the action mechanism of ginseng components on the molecule level. This review provides the usefulness of natural product, showing no toxic effects, as an radioprotective agent. Furthermore, the further clinical trials on radioprotection of ginseng need to be highly done to clarify its scientific application. The effective components of ginseng has been known as ginsenosides. Considering that each of these ginsenosides has pharmacological effect, it seems likely that non-saponin components might have radioprotective effects superior to those of ginsenosides, suggesting its active ingredients to be non-saponin series. These results also show that the combined effects of saponin and non-saponin components play an important role in the radioprotective effects of ginseng.

Exponential rise in the use of mobile communication devices has generated health concerns due to radiofrequency (RF) exposure due to its close proximity to the head. Calcium binding proteins like calretinin regulate the levels of calcium (Ca(2+)) which plays an important role in biological systems. Ginseng is known for maintaining equilibrium in the human body and may play a beneficial radioprotectant role against electromagnetic field (EMF) exposure. In the present study, we evaluated the radioprotective effects of red ginseng (RG) extract in a mouse model. Calretinin (CR) expression was measured using a free-floating immunohistochemical method in the hippocampus of mice after 835 MHz EMF exposure for 5 h/d for 5 d at specific absorption rate=1.6 W/kg for the different experimental groups. The control animals were treated with NaCl while the experimental animals received 10 mg/kg ginseng, or 30 mg/kg; EMF exposed mice were also treated with NaCl, 10 mg/kg ginseng (E10), or 30 mg/kg (E30). Decreases in CR immunoreactivity (IR) along with loss of CA1 and CA3 interneurons and infragranular cells were observed in the ENaCl group while such losses were not observed in the E10 and E30 groups. CR IR significantly increased in the RG-treated group compared to control and EMF-exposed groups treated with NaCl. The study demonstrates that RG extract can serve as a radioprotective agent that maintains Ca(2+) homeostasis and prevents neuronal loss in the brain hippocampal region caused by RF exposure.

Various approaches have been developed for diminishing the effects of radiation on normal tissues or enhancing tumor cell killing by ionizing radiation. Recently, there has been an increase in the interest in research on synthetic and/or natural radioprotective agents. An important potential use for these agents is to modify and improve the outcome of radiation therapy. The aim of this study was to examine the potential radioprotective role and antioxidant potency of the novel synthetic anticancer agent, quinoline sulfonamide (PIQSA) against tissue injury and oxidative stress induced by the exposure to gamma radiation and/or incidence of cancer in experimental animals. Mice (normal and bearing solid tumors) administered PIQSA (0.350 mg/kg body weight ip. three times a week for 21 days. At the last week of 30 days experimental period, an animal group was subjected to three successive doses of γ-radiation each of 2 Gy; another group was treated with combined administration of PIQSA 20 minutes before γ-irradiation. Some biochemical parameters (LPx, GSH, SOD, and CAT in liver homogenates, also plasma lipid profile (total lipids, total cholesterol, total triglycerides (TG), HDLc and LDLc were measured. To examine any adverse effect which could be attained by chemical treatment, liver enzymes (AST, ALT), and kidney function (creatinine and urea) were estimated in blood plasma, in addition to examination of some haematological indexes. The results indicated that the deleterious effects due to exposure to γ-radiation, and/or incidence of cancer on most of the estimated parameters could be controlled to a certain extent by administration of PIQSA to animals prior to irradiation. The results also confirmed that there were no significant adverse effects on mice due to the treatment with this chemical compound.

Radiotherapy has been extensively used in clinic for malignant tumors treatment. However, a severe challenge of it is that the ionizing radiation needed to kill tumors inevitably causes damage to surrounding normal tissues. Although some of the molecular radioprotective drugs, such as amifostine, have been used as clinical adjuvants to radio-protect healthy tissues, their shortcomings such as short systemic circulation time and fast biological clearing from the body largely hinder the sustained bioactivity. Recently, with the rapid development of nanotechnology in the biological field, the multifunctional nanomaterials not only establish powerful drug delivery systems to improve the molecular radioprotective drugs' biological availability, but also open a new route to develop neozoic radioprotective agents because some nanoparticles possess intrinsic radioprotective abilities. Therefore, considering these overwhelming superiorities, this review systematically summarizes the advances in healthy tissue radioprotection applications of multifunctional nanomaterials. Furthermore, this review also points out a perspective of nanomaterial designs for radioprotection applications and discusses the challenges and future outlooks of the nanomaterial-mediated radioprotection.