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Journal of Alternative and... Oct 2010The effective use of radiotherapy in cancer cure and palliation is compromised by the side-effects resulting from radiosensitivity of bordering normal tissues, which are... (Review)
Review
The effective use of radiotherapy in cancer cure and palliation is compromised by the side-effects resulting from radiosensitivity of bordering normal tissues, which are invariably exposed to the cytotoxic effects of ionizing radiation during treatment. In this situation, use of radioprotective compounds that can protect normal tissues against radiation injury are of immense use. In addition to protecting normal tissue these compounds will also permit use of higher radiation doses to obtain better cancer control and possible cure. However, to date, no ideal radioprotectors are available as most synthetic compounds are toxic at their optimal concentrations and have produced little success in clinics. Radiation ill-effects are principally the result of generation of free radicals, and the antioxidant compounds that counter them are supposed to be of immense use in preventing them. In Ayurveda, the traditional Indian system of medicine, several plants have been observed to avert/ameliorate free radical-mediated ailments--an effect that has been documented--and such plants have recently been the focus of attention. Aegle marmelos (L.) Correa (Bael), commonly known as bael, has been used since antiquity for treating various ailments, some of which are now known to be the result of oxidative stress. In studies spanning nearly a decade, it has been observed that bael prevented radiation-induced ill-effects, and the results of these studies indicate that it has the potential to be an effective, nontoxic radioprotective agent. In this current review, for the first time, an attempt is made to summarize these observations and to discuss the plausible reasons responsible for bael's radioprotective effects.
Topics: Aegle; Humans; Neoplasms; Phytotherapy; Plant Extracts; Radiation Tolerance; Radiation, Ionizing; Radiation-Protective Agents
PubMed: 20932194
DOI: 10.1089/acm.2009.0604 -
Oxidative Medicine and Cellular... 2016We have demonstrated that grape seed proanthocyanidins (GSPs) could effectively scavenge hydroxyl radical (•OH) in a dose-dependent manner. Since most of the ionizing...
We have demonstrated that grape seed proanthocyanidins (GSPs) could effectively scavenge hydroxyl radical (•OH) in a dose-dependent manner. Since most of the ionizing radiation- (IR-) induced injuries were caused by •OH, this study was to investigate whether GSPs would mitigate IR-induced injuries in vitro and in vivo. We demonstrated that GSPs could significantly reduce IR-induced DNA strand breaks (DSBs) and apoptosis of human lymphocyte AHH-1 cells. This study also showed that GSPs could protect white blood cells (WBC) from IR-induced injuries, speed up the weight of mice back, and decrease plasma malondialdehyde (MDA), thus improving the survival rates of mice after ionizing radiation. It is suggested that GSPs have a potential as an effective and safe radioprotective agent.
Topics: Animals; Apoptosis; Body Weight; Cell Line; Cell Survival; Comet Assay; Grape Seed Extract; Humans; Leukocyte Count; Male; Malondialdehyde; Mice, Inbred BALB C; Proanthocyanidins; Radiation, Ionizing; Radiation-Protective Agents; Survival Rate
PubMed: 27429710
DOI: 10.1155/2016/5706751 -
International Journal of Radiation... Jan 2019The risk of radiation exposure is considered to have increased in recent years. For convenience and simple administration, development of an effective orally...
17α-Ethinyl-androst-5-ene-3β, 17β-diol, a Novel Potent Oral Radioprotective Agent, Confers Radioprotection of Hematopoietic Stem and Progenitor Cells in a Granulocyte Colony-Stimulating Factor-Independent Manner.
PURPOSE
The risk of radiation exposure is considered to have increased in recent years. For convenience and simple administration, development of an effective orally administered radioprotective agent is highly desirable. The steroid 5-androstene-3β, 17β-diol (5-AED) has been evaluated as both a radioprotector and a radiomitigator in mice and nonhuman primates; however, poor oral bioavailability has limited its development. A variant compound-17α-ethinyl-androst-5-ene-3β, 17β-diol (EAD)-exhibits significant oral bioavailability. We investigated the radioprotective effects of EAD via oral administration in mice.
METHODS AND MATERIALS
Survival assays were performed in lethally (9.0-10.0 Gy) irradiated mice. Peripheral blood cell counts were monitored in lethally (9.5 Gy) or sublethally (6.5 Gy) irradiated mice. We performed histologic analysis of bone marrow (BM) and frequency and functional analysis of hematopoietic stem and progenitor cells in mice irradiated with 6.5 Gy. To investigate multilineage engraftment of irradiated hematopoietic stem cells after BM transplantation, competitive repopulation assays were conducted. Plasma granulocyte colony-stimulating factor was measured by enzyme-linked immunosorbent assay.
RESULTS
Oral administration of EAD on 3 consecutive days before irradiation conferred 100% survival in mice, against otherwise 100% death, at a 9.5-Gy lethal dose of total body irradiation. EAD ameliorated radiation-induced pancytopenia at the same dose. EAD augmented BM cellular recovery and colony-forming ability, promoted hematopoietic stem and progenitor cell recovery, and expanded the pool of functionally superior hematopoietic stem cells in the BM of sublethally irradiated mice. Unlike 5-AED, EAD did not increase granulocyte colony-stimulating factor levels in mice and exhibited no therapeutic effects on hematologic recovery after irradiation; nevertheless, its radioprotective efficacy was superior to that of 5-AED.
CONCLUSIONS
Our findings demonstrate the radioprotective efficacy of EAD and reveal that the 17α-ethinyl group is essential for its oral activity. Given its oral efficacy and low toxicity, EAD has potential as an optimal radioprotector for use by first responders, as well as at-risk civilian populations.
Topics: Animals; Bone Marrow Transplantation; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells; Male; Mice; Mice, Inbred C57BL; Radiation-Protective Agents; Whole-Body Irradiation
PubMed: 30103023
DOI: 10.1016/j.ijrobp.2018.08.002 -
Radiation Research Nov 1960
Topics: Diffusion; Humans; Radiation Protection; Radiation-Protective Agents; Spleen
PubMed: 13744631
DOI: No ID Found -
The Science of the Total Environment Jul 2021Radiation can be lethal at high doses, whereas controlled doses are useful in medical applications. Other applications include power generation, agriculture... (Review)
Review
Radiation can be lethal at high doses, whereas controlled doses are useful in medical applications. Other applications include power generation, agriculture sterilization, nuclear weapons, and archeology. Radiation damages genetic material, which is reflected in genotoxicity and can cause hereditary damage. In the medical field, it is essential to avoid the harmful effects of radiation. Radiation countermeasures and the need for radioprotective agents have been explored in recent years. Considering plants that evolve in radiative conditions, their ability to protect organisms against radiation has been studied and demonstrated. Crude extracts, fractioned extracts, isolated phytocompounds, and plant polysaccharides from various plants have been used in radioprotection studies, and their efficiency has been proven in various in vitro and in vivo experimental models. It is important to identify the mechanism of action to develop a potent plant-based radioprotective agent. To identify this protective mechanism, it is necessary to understand the damage caused by radiation in biological systems. This review intends to discuss the effects of ionizing radiation on biological systems and evaluate plant-based radioprotectants that have tested thus far as well as their mechanism of action in protecting against the toxic effects of radiation. From the review, the mechanism of radioprotection exhibited by the plant-based products could be understood. Meanwhile, we strongly suggest that the potential products identified so far should undergo clinical trials for critically evaluating their effects and for developing an ideal and compatible radioprotectant with no side-effects.
Topics: DNA Damage; Humans; Radiation Injuries; Radiation Protection; Radiation, Ionizing; Radiation-Protective Agents
PubMed: 34030282
DOI: 10.1016/j.scitotenv.2021.146431 -
Expert Opinion on Pharmacotherapy Mar 2001Amifostine (Ethyoltrade mark, Alza Pharmaceuticals) is an inorganic thiophosphate cytoprotective agent known chemically as ethanethiol, 2-[3-... (Review)
Review
Amifostine (Ethyoltrade mark, Alza Pharmaceuticals) is an inorganic thiophosphate cytoprotective agent known chemically as ethanethiol, 2-[3- aminopropyl)amino]dihydrogen phosphate. It is a prodrug of free thiol (WR-1065) that may act as a scavenger of free radicals generated in tissues exposed to cytotoxic drugs and binds to reactive metabolites of such drugs. Amifostine was originally developed as a radioprotective agent in a classified nuclear warfare project. Following declassification of the project it was evaluated as a cytoprotective agent against toxicity of the alkylating drugs and cisplatin. Differences in the alkaline phosphatase concentration of normal versus tumour tissues can result in greater conversion of amifostine in normal tissues. Inside the cell, WR-1065 provides an alternative target to DNA and RNA for the reactive molecules of alkylating or platinum agents and acts as a potent scavenger of the oxygen free radicals induced by ionizing radiation and some chemotherapy agents. Preclinical animal studies have demonstrated that the administration of amifostine protects against a variety of chemotherapy-related toxicities including cisplatin-induced nephrotoxicity, cisplatin-induced neurotoxicity, cyclophosphamide- and bleomycin-induced pulmonary toxicity and the cytotoxicities (including cardiotoxicity) induced by doxorubicin and related chemotherapeutic agents. Amifostine has been shown to protect a variety of animal species from lethal doses of radiation. Amifostine gives haematological protection from cyclophosphamide, carboplatin, mitomycin C, fotemustine and radiotherapy; renal and peripheral nerve protection from cisplatin; mucosa, skin and salivary gland protection from radiotherapy. Multiple Phase I studies were carried out with amifostine in combination with chemotherapy for various neoplasms. Appropriate doses of amifostine were found to be 740 - 910 mg/m(2) in single-dose regimens and 340 mg/m(2) in multiple-dose regimens. In radioprotection, doses are generally 200 - 350 mg/m(2). For all these characteristics, amifostine has been recently approved and suggested in ASCO clinical practice guidelines as a radioprotector for head and neck cancer treatment and supportive agent during cisplatin-based chemotherapy, in lymphomas and solid tumours. Moreover, its spectrum of possible applications is enlarging. As data have been provided indicating that amifostine stimulates haematopoiesis, it has been employed with intriguing results in the treatment of myelodysplastic syndromes (MDS).
Topics: Amifostine; Animals; Clinical Trials as Topic; Humans; Radiation-Protective Agents
PubMed: 11336600
DOI: 10.1517/14656566.2.3.479 -
Expert Opinion on Drug Discovery Jul 2019: There are at the minimum two major, quite different approaches to advance drug discovery. The first being the target-based drug discovery (TBDD) approach that is... (Review)
Review
: There are at the minimum two major, quite different approaches to advance drug discovery. The first being the target-based drug discovery (TBDD) approach that is commonly referred to as the molecular approach. The second approach is the phenotype-based drug discovery (PBDD), also known as physiology-based drug discovery or empirical approach. : The authors discuss, herein, the need for developing radiation countermeasure agents for various sub-syndromes of acute radiation syndromes (ARS) following TBDD and PBDD approaches. With time and continuous advances in radiation countermeasure drug development research, the expectation is to have multiple radiation countermeasure agents for each sub-syndrome made available to radiation exposed victims. : The majority of the countermeasures currently being developed for ARS employ the PBDD approach, while the TBDD approach is clearly under-utilized. In the future, an improved drug development strategy might be a 'hybrid' strategy that is more reliant on TBDD for the initial drug discovery via large-scale screening of potential candidate agents, while utilizing PBDD for secondary screening of those candidates, followed by tertiary analytics phase in order to pinpoint efficacious candidates that target the specific sub-syndromes of ARS.
Topics: Acute Radiation Syndrome; Animals; Drug Development; Drug Discovery; Humans; Radiation-Protective Agents
PubMed: 31008662
DOI: 10.1080/17460441.2019.1604674 -
Current Radiopharmaceuticals 2022Natural products can be used as radioprotector agents because of containing phenolic compounds and several flavonoids with antioxidant properties. When the normal cells...
INTRODUCTION
Natural products can be used as radioprotector agents because of containing phenolic compounds and several flavonoids with antioxidant properties. When the normal cells are exposed to ionizing radiation, they generate free radicals and reactive oxygen species that can cause damage in DNA, which leads to cellular dysfunction or even cell death. However, it is necessary to identify new radioprotective agents to protect normal cells. Ferulago angulata (F. angulata), a medicinal plant, can be used as a new radioprotective agent.
PURPOSE
In this study, the radioprotective effect of F. angulata was evaluated against genotoxicity and oxidative stress induced by ionizing radiation in human blood lymphocytes.
METHODS
The antioxidant activity of F. angulata was assayed using FRAP and DPPH methods. Then, the human blood samples were incubated with F. angulata at different concentrations (25, 50, 100, and 200 μM) and subsequently exposed to IR at a dose of 2Gy. The radioprotective effect of F. angulata on the exposed cells was assessed by the micronucleus (MN) method. Also, biomarkers of oxidative stress in the exposed cells were evaluated by malondialdehyde (MDA) and superoxide dismutase (SOD) methods.
RESULTS
Our findings showed that F. angulata reduced the frequency of MN induced by IR in exposed cells. At a 200 μM concentration of F. angulata, the maximum reduction in the frequency of MN (63.11%) was observed that demonstrated a high degree of radioprotection. Afterward, pretreatment at 200 μM concentration of F. angulata inhibited oxidative stress in irradiated lymphocytes, leading to a reduction in MN frequency and MDA levels while SOD activity was enhanced in the exposed cells.
CONCLUSION
F. angulata as a natural radioprotective agent can protect normal cells against reactive oxygen species and genetic damage induced by IR.
Topics: Antioxidants; Apiaceae; DNA Damage; Humans; Radiation-Protective Agents; Radiopharmaceuticals; Reactive Oxygen Species; Superoxide Dismutase
PubMed: 33902426
DOI: 10.2174/1874471014666210426111806 -
Bulletin of Experimental Biology and... Sep 2017We studied radioprotective effects of a preparation based on yeast RNA and its influence on therapeutic efficiency of ionizing radiation against transplanted tumors....
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 (Cs) in a lethal dose (LD) 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.
Topics: Animals; Dose-Response Relationship, Radiation; Leukemia; Lung Neoplasms; Male; Mice; Neoplasm Metastasis; RNA, Fungal; Radiation-Protective Agents; Saccharomyces cerevisiae
PubMed: 28948545
DOI: 10.1007/s10517-017-3868-x -
Free Radical Biology & Medicine Dec 2019The adverse effects of ionizing radiation (IR) on biological tissues are mediated via increased production of reactive oxygen species (ROS) often resulting in...
The adverse effects of ionizing radiation (IR) on biological tissues are mediated via increased production of reactive oxygen species (ROS) often resulting in life-threatening injuries. The effects of ionizing radiation on cells include the formation of ROS, DNA single-strand breaks, double-strand breaks, and extensive base modifications inducing the complex DNA damage. The capacity to endure the radiation insult lies in the biochemical mechanisms and structural properties in many bacterial species such as Deinococcus radiodurans and Thermococcus radiotolerans. In addition, a mechanistic link has established between the presence and accumulation of short peptides and Mn in the protection of bacteria (Deinococcus radiodurans) from the harmful ionizing radiation. This paradigm has opened up novel avenues of radioprotection in diverse settings and systems for human application. We hereby report a new bifunctional system that comprises of thiol groups in the form of Glutathione (GSH), and manganese to mimic the above system for radioprotection. The present study, therefore, adopts a novel approach to use GSH complexed Mn, and this conjugated system is complying with the prerequisite for radioprotection as seen in the above mechanism. This unique conjugate DT(GS)Mn(II) was evaluated for its efficacy invitro and invivo. Radioprotective efficacy of DT(GS)Mn(II) on NIH/3T3 cells revealed that compound could significantly protect cells against radiation-induced toxicity as compared to the standard compound N-acetyl cysteine. Pre-treatment of DT(GS)Mn(II) increased the survival of mice by 50% compared to radiation alone treatment group. A significant decrease in cytochrome c levels in the group pre-treated with test compound (0.50 ± 0.14) compared to radiation alone group (1.60 ± 0.07) was observed. DT(GS)Mn(II) attenuated radiation induced apoptosis by promoted expression of anti-apoptotic Bcl-2 along with suppression of cyt-c release and augmented cell survival following irradiation. A distinct improvement in villi length was observed in the group treated with DT(GS)Mn(II) with an average of 1546 ± 61 μm versus 763 ± 154 μm for radiation alone group. The present findings suggested DT(GS)Mn(II) is a promising radioprotective agent and exerts it protective effect both invitro and invivo systems by decreasing radiation induced cytotoxicity.
Topics: Abnormalities, Radiation-Induced; Acetylcysteine; Animals; Cell Survival; DNA Damage; DNA Repair; Glutathione; Humans; Manganese; Mice; Oxidative Stress; Peptidomimetics; Radiation, Ionizing; Radiation-Protective Agents
PubMed: 31550530
DOI: 10.1016/j.freeradbiomed.2019.09.023