Early results of the screening program for radioprotectors

Brown, Darrell Q.; Pittock, J; Rubinstein, J

doi:10.1016/0360-3016(82)90685-x

Cited by 51 publications

(13 citation statements)

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“…In addition to its high efficacy in ameliorating xerostomia resulting from irradiation (4,5), high frequencies of deleterious side effects (nausea, cutaneous reactions, hypotension, etc.) and even tumor radioprotection have been reported, which limit its use (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Research progress in the radioprotective effect of superoxide dismutase

et al. 2012

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Irradiation from diverse sources is ubiquitous and closely associated with human activity. Radiation therapy (RT), an important component of the multiple radiation origins, contributes significantly to oncotherapy by killing tumor cells. On the other hand, RT can also cause some undesired normal tissue injuries that afflict numerous cancer patients. Although many promising radioprotective agents are emerging, few of them have entered the market successfully due to various limitations. At present, the most accepted hypothesis for the radiation-caused injury involves reactive oxygen species (ROS) generation. Superoxide dismutase (SOD), the unique enzyme responsible for the dismutation of superoxide radicals, is expected to occupy an indispensable position in the treatment of ROS-mediated tissue injuries originating from exposure to radiation. This review focuses on the mechanism of radioprotection by SOD at the tissue or organ level, cellular level, and molecular level, respectively, in order to provide references for further investigation of radiation injury and development of new radioprotectors.

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Section: Introductionmentioning

confidence: 99%

Research progress in the radioprotective effect of superoxide dismutase

et al. 2012

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“…7,15 Over the past few decades, a number of active compounds with potential radioprotective effects have been studied at the cellular level and in animal models. [34][35][36] In particular, sulfur compounds have been tested in animal models for their possible protective effects against inflammation induced by radiation. 37,38 In the present study, we used AMS, an organic sulfur compound from garlic, that is known to act as an antitumor agent by inhibiting cytochrome P450 2E1 protein as well as an anti-inflammatory agent by suppressing nitric oxide production in LPS-stimulated macrophages.…”

Section: Discussionmentioning

confidence: 99%

Allylmethylsulfide Down-Regulates X-Ray Irradiation-Induced Nuclear Factor-κB Signaling in C57/BL6 Mouse Kidney

Lee

Chung

Kim

et al. 2009

Journal of Medicinal Food

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Allylmethylsulfide (AMS), a volatile organosulfur derivative from garlic, has been shown to have radioprotective effects in radiation-challenged cell and animal models, but the mechanism of radioprotection is not well understood. To determine the mechanism of radioprotection in an in vivo model, we first verified the antioxidant capacity of AMS using 2,2'-azobis(2-amidinopropane) dihydrochloride-induced human embryonic kidney 293T cells by measuring reactive oxygen species generation, reduced glutathione, protein tyrosine kinase/protein tyrosine phosphatase balance, and nuclear factor-kappaB (NF-kappaB) protein levels. We then investigated the protective effects of AMS (55 and 275 micromol/kg, intraperitoneal treatment) on 15 Gy X-ray-irradiated mouse kidney. The results showed that AMS decreased the free radical-induced lipid peroxidation in mice exposed to X-rays. Moreover, the antioxidative AMS suppressed the activation of NF-kappaB and its dependent genes such as vascular cell adhesion molecule-1, inducible nitric oxide synthase, and cyclooxygenase-2 through inhibition of IkappaBalpha phosphorylation and activation of IkappaB kinase alpha/beta and mitogen-activated protein kinases (MAPKs). Based on these results, AMS may be a useful radioprotective agent by down-regulating the MAPKs and NF-kappaB signaling pathway that can be induced via X-ray irradiation.

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“…In a preclinical study, WR-2721 demonstrated a DRF of 2.7 for H-ARS and 1.8 for GI-ARS, when administered intraperitoneally (ip) at a dose of 500 mg/kg to mice before irradiation ( Table 2) [48][49][50][51]. The drug dose used was relatively high in terms of adverse sideeffects, as LD 50 dose for the drug alone was 704 mg/kg [48].…”

Section: Article Highlightsmentioning

confidence: 99%

“…The usual toxic effects of amifostine are hypotension, emesis, somnolence, and sneezing in patients who received [48] 500 -1.64 [49] 400 2.25 - [50] 365 2.29 1.55 [51] single or multiple doses [46]. Other minor adverse effects are malaise, hypocalcemia, metallic taste, hiccups, chills, flushed feeling, idiosyncratic reactions, fever, and/or rash.…”

Section: Mechanisms and Toxicities Of Amifostinementioning

confidence: 99%

The efficacy and safety of amifostine for the acute radiation syndrome

Singh

Seed²

2019

Expert Opinion on Drug Safety

119

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Introduction: A radiation countermeasure that can be used prior to radiation exposure to protect the population from the harmful effects of radiation exposure remains a major unmet medical need and is recognized as an important area for research. Despite substantial advances in the research and development for finding nontoxic, safe, and effective prophylactic countermeasures for the acute radiation syndrome (ARS), no such agent has been approved by the United States Food and Drug Administration (FDA). Area covered: Despite the progress made to improve the effectiveness of amifostine as a radioprotector for ARS, none of the strategies have resolved the issue of its toxicity/side effects. Thus, the FDA has approved amifostine for limited clinical indications, but not for non-clinical uses. This article reviews recent strategies and progress that have been made to move forward this potentially useful countermeasure for ARS. Expert opinion: Although the recent investigations have been promising for fielding safe and effective radiation countermeasures, additional work is needed to improve and advance drug design and delivery strategies to get FDA approval for broadened, non-clinical use of amifostine during a radiological/nuclear scenario. ARTICLE HISTORY

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Early results of the screening program for radioprotectors

Cited by 51 publications

References 1 publication

Research progress in the radioprotective effect of superoxide dismutase

Research progress in the radioprotective effect of superoxide dismutase

Allylmethylsulfide Down-Regulates X-Ray Irradiation-Induced Nuclear Factor-κB Signaling in C57/BL6 Mouse Kidney

The efficacy and safety of amifostine for the acute radiation syndrome

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