A Fusion of Field and Laboratory Studies in the Investigation of Arsenic

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  • KUMAGAI Yoshito
    Doctoral Programs in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba

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  • ヒ素研究におけるフィールドサイエンスと実験科学の融合
  • ヒソ ケンキュウ ニ オケル フィールドサイエンス ト ジッケン カガク ノ ユウゴウ

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  Arsenic is ubiquitously distributed in nature throughout Earth's crust and thus the major source of exposure to this metalloid for the general population is naturally polluted drinking water from wells. In East Asia, more than 30 million people are chronically exposed to arsenic. Interestingly, the manifestations of vascular diseases caused by prolonged exposure to arsenic are consistent with those induced by impaired production of endothelium-derived nitric oxide (NO). However, no information has been available on the relation between NO synthesis and chronic arsenic poisoning in humans. A cross-sectional study in an endemic area of chronic arsenic poisoning in Inner Mongolia and experimental animal studies indicated that long-term exposure to arsenic by drinking water causes reduction of NO production in endothelial cells. Subsequent examinations with rabbits showed that decreased NO production during arsenic exposure is, at least in part, due to an “uncoupling” of endothelial NO synthase evoked by decreased levels of (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4), a cofactor of the enzyme, leading to endothelial dysfunction. Furthermore, an intervention study in the area of chronic arsenic poisoning in Inner Mongolia suggested that decreased NO levels and peripheral vascular disease in arsenosis patients can be reversed by exposure cessation. In our cellular experiments, we found that arsenic exposure causes adaptive responses against oxidative stress and arsenic cytotoxicity through Nrf2 activation. This review summarizes the results of our recent studies on a fusion of field and laboratory studies on the chronic arsenic poisoning and cellular protection against the metalloid.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 129 (10), 1177-1185, 2009-10-01

    The Pharmaceutical Society of Japan

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