• Journal of Radiation Protection and Research
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• v.8 no.2
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• pp.1-7
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• 1983

S-2-($\omega-aminoalkylamino) ethyl dihydrogen phosphorothioates and S-2-($\omega$-aminoalkylamino) ethyl isothiuronium bromides were prepared from easily available starting compounds via convenient synthetic processes. The isothiuronium derivatives showed extreme drug toxicities as compared to that of AET, which seemed to be due to an intramolecular rearrangement of these compounds. The propyl derivative of the phosphorothioate could show better radioprotective effect than those of AET and WR-638, whereas the ethyl derivative of the equivalent drug dose revealed far less protective effect. The correlation between radioprotective effects, drug toxicities, and chemical structures were discussed through infrared spectroscopy.

• Journal of Radiation Protection and Research
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• v.7 no.1
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• pp.11-16
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• 1982

Cysteamine(Mercaptoethyiamine, MEA), S,2-Aminoethylisothiouronium Bromide. HBr (AET), and S-(2-Aminoethyl) Dihydrogen Phosphorothioate (WR-638) were prepared and radioprotective effects of these chemicals and their combinations against $^{60}Co$ ${\gamma}-ray$ radiation were studied ,in irradiated ICR mice. Intraperitonially administered chemicals or their combinations resulted drug deaths in cases of MEA, AET, and their combinations, whereas there were a slight or no drug death in cases of WR-638 and the combination of AET with WR-638. All tested chemicals and their combinations yielded radioprotective effects against $^{60}Co$ $\gamma-ray$ radiation. An additive radioprotection effect was observed in case of the combination of AET with WR-638.

• Radiation Oncology Journal
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• v.33 no.3
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• pp.256-260
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• 2015

Purpose: Mefenamic acid (MEF) as a non-steroidal anti-inflammatory drug is used as a medication for relieving of pain and inflammation. Radiation-induced inflammation process is involved in DNA damage and cell death. In this study, the radioprotective effect of MEF was investigated against genotoxicity induced by ionizing radiation in human blood lymphocytes. Materials and Methods: Peripheral blood samples were collected from human volunteers and incubated with MEF at different concentrations (5, 10, 50, or $100{\mu}M$) for two hours. The whole blood was exposed to ionizing radiation at a dose 1.5 Gy. Lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis blocked binucleated lymphocyte. Results: A significant decreasing in the frequency of micronuclei was observed in human lymphocytes irradiated with MEF as compared to irradiated lymphocytes without MEF. The maximum decreasing in frequency of micronuclei was observed at $100{\mu}M$ of MEF (38% decrease), providing maximal protection against ionizing radiation. Conclusion: The radioprotective effect of MEF is probably related to anti-inflammatory property of MEF on human lymphocytes.

• Journal of Radiation Protection and Research
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• v.10 no.2
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• pp.122-129
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• 1985

S-2, W-diaminopentyl isothiuronium bromide and relevant thiophosphate derivative were prepared starting from both phthalimide and l-ornithinic acid. Drug toxicities of the prepared isothiuronium bromide and S-2-(W-aminoalkylamino) ethyl isothiuronium bromides were tested through ICR male mice, 4 and 8 weeks old and weighing $25{\sim}35g$. The former compound was found to be less toxic than those of latter compounds. This difference of drug toxicities seemed to be originated from their chemical structures, which were examined through IR Spectrometry Radioprotective effects of these compounds were discussed through relevant research data and diaminopentyl derivatives are considered to be a potent radioprotectant with low drug toxicity.

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.217-220
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• 1988

At present, the treatment of the radiation-induced diseases are only performing by the palliative treatment technique. Moreover, radioprotective drugs are a little toxic for human being and this seriously limits their application with various complication in clinical uses. Accordingly, new radioprotectors need developing. In our Lab., we synthesized trithioformaldehyde (TTFA), containing three sulfur atom, and examined the effect on mouse jejunal crypt cells after irradiation. Mice treated with TTF A (2.0 g/ kg) showed 78% survival ratio at 30 day after 800 rad irradiation. 1.0 g/kg and 2.0 g/kg of TTF A increased resistance of jejunal crypt cells to single doses of radiation by protection factors of 1.17 and 1.23, respectively.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.145-150
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• 1990

Mesna has been used with ifosfamide to prevent urotoxicity in the treatment of testicular cancers. This drug also protected the toxicities of adriamycin without compromising cytostatic activity. With an idea of radioprotective role of sulfhydryl group of radioprotectors and of mesna decreasing the toxic effect of adriamycin which produces free radicals, mesna and radiation were administered to mice to study the protective effect of this drug and to identify the difference in regenerative capacity of the germ cells in the testis between radiation-treated and both mesna-and radiation-treated groups. The shape and numbers of spermatogenic cells in the seminiferous tubules were examined every week after irradiation. In both groups, initial reduction and later recovery in germ cell numbers and shape was observed. The lowest germ cell number was found around three weeks after irradiation. Mean germ cell number of the mesna-treated group was significantly higher than radiation-treated group at all observed periods (p<0.05). More competent regeneration was present in mesna-treated group. These results suggest that mesna protect the testis from radiation injury. Further study will be necessary to identify whether mesna protects other tissues from radiation and it does not hamper tumor control.

• Journal of Pharmaceutical Investigation
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• v.17 no.2
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• pp.55-60
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• 1987

WR 2721 (S-2-(3-aminopropylaminoethylphosphorothioate) is a radioprotective drug that is now undergoing clinical trials in the United States and Japan. a liquid chromatographic electrochemical method for the determination of WR 2721 an WR 3689 [S-2-(3-methylaminopropylamino)ethylphorothioate] in human plasma was developed in this study. This method includes the use of a Hg/Au electrochemical detector and a cyano column for the direct measurement of WR 2721 and WR 3689 in plasma. An analog of WR 2721, WR 149846 was used as an internal standard. WR 2721 and WR 3689 could be well separated from the solvent front, with a mobile phase of acetonitrile-water (20:80), 0.1M acetic acid and 1.2 mM sodium octane sulfonate. This method was shown to be precise. Both intra-day and inter-day results were within 10% CV. Also, sample preparation was fairly simple. Since WR 2721 and WR 3689 were unstable at room temperature, it was essential to use an automatic sample processor with a refrigerator, especially for carrying out routine analyses.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.463-466
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• 2016

Glioblastoma (GBM) is the most common and aggressive type of primary brain neoplasm. The current standard therapy for GBM consists of maximal surgical resection within safe limits, followed by radiation therapy (RT) and chemotherapy with temozolomide. Despite advances in treatment, the prognosis of GBM remains poor. Epileptic seizure is one of the most common symptoms in patients with GBM. Valproic acid (VPA), a histone deacetylase inhibitor, is often used as an anti-epileptic drug in patients with brain neoplasms due to its effectiveness and low toxicity profile. Several in vivo and in vitro studies have indicated that VPA has radiosensitizing effects for gliomas and radioprotective influence on normal brain tissue or hippocampal neurons. The results of several retrospective studies have also indicated potential benefit to improve survival of patients with GBM. Moreover, the promising treatment results of a phase 2 trial of concurrent radiation therapy, temozolomide, and VPA for patients with GBM have been recently reported. The use of VPA in patients with GBM has thus recently receiving more attention. In this article, we review the role of VPA in radiation therapy for GBM, focusing on the clinical evidence.