Efficacy of a radioprotective drug, 2-mercaptopropionylglycine (MPG), in its free form and after its encapsulation into liposomes have been studied in normal and cancer bearing mice. Cancer was induced in micy by oral administration of aqueous extract of betel nut (AEBN) for 3 months. Radioprotection afforded by free MPG and liposome encapsulated MPG (LEM) in normal and cancerous tissue were evaluated by monitoring levels of glutathione (GSH) and γ-glutamyltranspeptidase (GGT) enzyme and state of structural organization of chromatin. The results of our studies reveal that in cancerous tissues LEM afforded better radioprotection than the free form of MPG. (orig.)
The radioprotective action and cytotoxicity of various sulfhydryl compounds; 2-mercaptopropionylglycine (MPG), 2-mercaptopropionylglycine-amide (MPG-amide), 2-mercaptopropionylphenylalanine (MPPA), 2-mercaptopropionylphenylglycine (MPPG), 3-mercaptopropionylglycine (3-MPG), AET, cysteine and cysteamine were compared in irradiated and unirradiated mouse L cells using colony forming ability as a criterion. It was indicated that the sulfhydryl compounds divided into three classes, according to their radioprotective action and toxicity. Most effective radioprotection was obtained by cysteamine and cysteine, followed by AET and MPG-amide in that order. Toxicity of these sulfhydryl compounds were generally observed in concentrations in the range of 0.1 - 2 mM, while they are much less toxic and effectively radioprotective in higher concentration, especially in cysteamine and cysteine. On the other hand, MPG, MPPA, MPPG, and 3-MPG were all non-toxic and generally ineffective in protecting irradiated cells, except that MPG in concentrations around 0.02 mM and 15 mM and MPPA and 3-MPG around 15 mM have a slight but significant protective action. (auth.)
Since cysteine was found to protect lethally irradiated rats, sulfhydryl compounds that provide protection of laboratory animals against lethal doses of ionizing radiations have also been given much attention. The SH compounds have been the most extensively investigated, and β-aminoethylisothiouronium (AET) and cysteamine have been selected as being representative of those drugs that are highly protective. However, clinical application is limited, as the toxicity of these compounds is high. In a series of experiments to reevaluate radioprotective agents with low toxicity, the authors found that 2-mercaptopropionylglycine (MPG) and adrenochrome monoguangylhydrazone methanesulfonate (AMM) have a potent radioprotector effect in a dose far below their toxic doses in both mice and humans. Recently, the development of effective thiophosphate derivatives of cysteamine, namely WR-2721 [S-2-(3-amino-propylaminoethyl)phosphorothioate] by the U.S. Army Medical Research and Development Commands, led to a reevaluation of these compounds and their potential in radiotherapy. Initial investigations indicated that WR-2721 provided a considerable degree of radioprotection to normal tissues. This compound provided excellent protection for normal tissues (DMF = 2-2.5) but little protection for the transplanted tumor. Thus this drug may have a differential protection in vivo and may be useful for improving the therapeutic ratio in cancer radiotherapy. The results of animal and chemical experiments in Japan are summarized herein
Experiments were undertaken to study the goblet cell changes in the jejunum of mice irradiated in the presence and absence of the protective drug 2-mercaptopropionylglycine (MPG). One group of adult Swiss albino mice of 6 to 8 weeks was injected with the drug (MPG) intraperitoneally and a second group was injected with distilled water in the same manner and served as a control. 15-30 minutes after injection animals from both the groups were exposed to a Co-60 source to give a total dose of 1000 R at the rate of 25 R/min. Three animals from each group were sacrificed at different successive intervals. 5μ paraffin sections of the jejunum were prepared and goblet cells were counted in the crypt and villus region. The results from the two groups were compared. The results from MPG treated mice indicated that there was a protection from the radiation-induced changes. The drug accelerated the regeneration process leading to the restoration of normal number of goblet cells by the last interval studied. (orig.)
Capillary electrophoresis coupled with inductively coupled mass spectrometry as an alternative to cloud point extraction based methods for rapid quantification of silver ions and surface coated silver nanoparticles.
Qu, Haiou; Mudalige, Thilak K; Linder, Sean W
Speciation and accurate quantification of ionic silver and metallic silver nanoparticles are critical to investigate silver toxicity and to determine the shelf-life of products that contain nano silver under various storage conditions. We developed a rapid method for quantification of silver ions and silver nanoparticles using capillary electrophoresis (CE) interfaced with inductively-coupled plasma mass spectrometry (ICPMS). The addition of 2-mercaptopropionylglycine (tiopronin) to the background electrolyte was used to facilitate the chromatographic separation of ionic silver and maintain the oxidation state of silver. The obtained limits of detection were 0.05 μg kg(-1) of silver nanoparticles and 0.03 μg kg(-1) of ionic silver. Nanoparticles of varied sizes (10-110 nm) with different surface coating, including citrate acid, lipoic acid, polyvinylpyrrolidone and bovine serum albumin (BSA) were successfully analyzed. Particularly good recoveries (>93%) were obtained for both ionic silver and silver nanoparticle in the presence of excess amount of BSA. The method was further tested with six commercially available dietary supplements which varied in concentration and matrix components. The summed values of silver ions and silver nanoparticles correlated well with the total silver concentration determined by ICPMS after acid digestion. This method can serve as an alternative to cloud point extraction technique when the extraction efficiency for protein coated nanoparticles is low. PMID:26724893
Chemical radiation protection in rodents was first discovered in 1949 and clinical application in cases of acute radiation sickness seemed to be promising. Numerous chemicals were screened in various laboratories, but clinically available chemical protectors were not discovered. It was concluded in 1962 that although a number of compounds may be capable of efficient protection of mice when given before exposure to X or γ rays, none could be considered a practical agent for protection of humans. On the basis of synthesis, stability, and effectiveness of oral administration, as well as dose-reduction properties, S-(2-aminoethyl)isothiouronium (AET) would seem to be the drug of choice. However, preliminary tests of AET in humans indicated that the toxicity may be far too great. New chemical protectors have been reported, following two different lines of research in Japan and in the United States. In Japan, an adrenochrome derivative, adrenochrome monoguanylhydrazone methanesulfonate (AMM) and a new sulfhydrl compound, 2-mercaptopropionylglycine (MPG), which are both effective in much lower doses than their toxic dose in mice, were reported. In the United States, after a large screening of various kinds of derivatives of cysteamine, WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid was reported to have a very high dose-reduction factor of 2.5 or more, thus effective even at a less toxic dose. To make use of these chemicals in cases of cancer radiotherapy, differential protection between tumor and normal tissues has to be established. Studies along this line have been also carried out with WR-2721 and MPG. The results obtained so far are promising for the improvement of radiotherapy. In this chapter, experimental studies on these chemicals are reviewed, emphasizing the authors own research