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Selenium-mediated arsenic excretion in mammals: a synchrotron-based study of whole-body distribution and tissue-specific chemistry
Metallomics ( IF 2.9 ) Pub Date : 2017-10-09 00:00:00 , DOI: 10.1039/c7mt00201g
Olena Ponomarenko 1, 2, 3, 4, 5 , Paul F. La Porte 6, 7, 8, 9, 10 , Satya P. Singh 1, 2, 3, 4, 5 , George Langan 8, 9, 11 , David E. B. Fleming 5, 12, 13, 14 , Julian E. Spallholz 9, 15, 16, 17 , Mohammad Alauddin 9, 18, 19, 20 , Habibul Ahsan 7, 8, 9, 21 , Selim Ahmed 22, 23, 24, 25 , Jürgen Gailer 5, 26, 27, 28 , Graham N. George 1, 2, 3, 4, 5 , Ingrid J. Pickering 1, 2, 3, 4, 5
Affiliation  

Arsenicosis, a syndrome caused by ingestion of arsenic contaminated drinking water, currently affects millions of people in South-East Asia and elsewhere. Previous animal studies revealed that the toxicity of arsenite essentially can be abolished if selenium is co-administered as selenite. Although subsequent studies have provided some insight into the biomolecular basis of this striking antagonism, many details of the biochemical pathways that ultimately result in the detoxification and excretion of arsenic using selenium supplements have yet to be thoroughly studied. To this end and in conjunction with the recent Phase III clinical trial “Selenium in the Treatment of Arsenic Toxicity and Cancers”, we have applied synchrotron X-ray techniques to elucidate the mechanisms of this arsenic–selenium antagonism at the tissue and organ levels using an animal model. X-ray fluorescence imaging (XFI) of cryo-dried whole-body sections of laboratory hamsters that had been injected with arsenite, selenite, or both chemical species, provided insight into the distribution of both metalloids 30 minutes after treatment. Co-treated animals showed strong co-localization of arsenic and selenium in the liver, gall bladder and small intestine. X-ray absorption spectroscopy (XAS) of freshly frozen organs of co-treated animals revealed the presence in liver tissues of the seleno bis-(S-glutathionyl) arsinium ion, which was rapidly excreted via bile into the intestinal tract. These results firmly support the previously postulated hepatobiliary excretion of the seleno bis-(S-glutathionyl) arsinium ion by providing the first data pertaining to organs of whole animals.

中文翻译:

哺乳动物中硒介导的砷排泄:基于同步加速器的全身分布和组织特异性化学研究

砷中毒是一种因摄入受砷污染的饮用水而引起的综合症,目前已影响到东南亚及其他地区的数百万人。先前的动物研究表明,如果硒与亚硒酸盐并用,则基本上可以消除亚砷酸盐的毒性。尽管随后的研究为这种惊人的拮抗作用的生物分子基础提供了一些见识,但使用硒补充剂最终导致砷的解毒和排泄的生化途径的许多细节尚未得到彻底研究。为此,并结合最近的III期临床试验“硒在砷中毒和癌症的治疗中”,我们使用动物模型通过同步加速器X射线技术在组织和器官水平上阐明了这种砷-硒拮抗作用的机制。注射了亚砷酸盐,亚硒酸盐或这两种化学物质的实验室仓鼠的冷冻干燥全身切片的X射线荧光成像(XFI),为处理后30分钟的两种类金属的分布提供了见识。共同治疗的动物在肝脏,胆囊和小肠中显示出强烈的砷和硒共定位。共同治疗动物的新鲜冷冻器官的X射线吸收光谱法(XAS)表明,硒油中的硒(-)在肝脏组织中存在 在治疗后30分钟提供了两种类金属的分布的见解。共同治疗的动物在肝脏,胆囊和小肠中显示出强烈的砷和硒共定位。共同治疗动物的新鲜冷冻器官的X射线吸收光谱法(XAS)表明,硒油中的硒(-)在肝脏组织中存在 在治疗后30分钟提供了两种类金属的分布的见解。共同治疗的动物在肝脏,胆囊和小肠中显示出强烈的砷和硒共定位。共同治疗动物的新鲜冷冻器官的X射线吸收光谱法(XAS)表明,硒油中的硒(-)在肝脏组织中存在S-谷胱甘肽)ion离子,它通过胆汁迅速排入肠道。这些结果通过提供有关整只动物器官的第一批数据,坚决支持了硒二-(S-谷胱甘肽)ion离子的先前假定的肝胆排泄。
更新日期:2017-11-16
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