Keith Jason D, Pacey Gilbert E, Cotruvo Joseph A, Gordon Gilbert
Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA.
Toxicology. 2006 Apr 17;221(2-3):225-8. doi: 10.1016/j.tox.2006.02.003. Epub 2006 Mar 10.
This study was designed to identify and quantify the effects of reducing agents on the rate of bromate ion reduction in real and synthetic gastric juice. This could be the first element in the sequence of a pharmacokinetic description of the fate of bromate ion entering the organism, being metabolized, and subsequently being tracked through the system to the target cell or eliminated. Synthetic gastric juice containing H+ and Cl- did exhibit reduced bromate ion levels, but at a rate that was too slow for a significant amount of bromate to be reduced under typical stomach retention time conditions. The reaction orders for Cl- and H+ were 1.50 and 2.0, respectively. Addition of the reducing agents hydrogen sulfide (which was shown to be present and quantified in real gastric juice), glutathione, and/or cysteine increased the rate of bromate ion loss. All of the reactions showed significant pH effects. Half-lives as short as 2 min were measured for bromate ion reduction in 0.17 M H+ and Cl- and 10(-4) M H2S. Therefore, the lifetime of bromate ion in solutions containing typical gastric juice concentrations of H+, Cl-, and H2S is 20-30 min. This rate should result in as much as a 99% reduction of bromate ion during its residence in the stomach. Bromate ion reduction in real gastric juice occurred at a rapid rate. A comparison of real and synthetic gastric juice containing H+, Cl-, cysteine, glutathione, and hydrogen sulfide showed that the component most responsible for the considerable decrease of the concentration of bromate ion in the stomach is hydrogen sulfide.
本研究旨在确定并量化还原剂对真实胃液和合成胃液中溴酸根离子还原速率的影响。这可能是对进入生物体、被代谢、随后在系统中被追踪至靶细胞或被清除的溴酸根离子命运进行药代动力学描述序列中的首个要素。含有H⁺和Cl⁻的合成胃液确实显示出溴酸根离子水平降低，但在典型的胃滞留时间条件下，其降低速率过慢，无法使大量溴酸根被还原。Cl⁻和H⁺的反应级数分别为1.50和2.0。添加还原剂硫化氢（已证实在真实胃液中存在并可定量）、谷胱甘肽和/或半胱氨酸可提高溴酸根离子的损失速率。所有反应均显示出显著的pH效应。在0.17 M H⁺、Cl⁻和10⁻⁴ M H₂S中，溴酸根离子还原的半衰期短至2分钟。因此，在含有典型胃液浓度的H⁺、Cl⁻和H₂S的溶液中，溴酸根离子的寿命为20 - 30分钟。该速率应导致溴酸根离子在胃中停留期间减少多达99%。真实胃液中溴酸根离子的还原速率很快。对含有H⁺、Cl⁻、半胱氨酸、谷胱甘肽和硫化氢的真实胃液和合成胃液进行比较表明，对胃中溴酸根离子浓度显著降低最负责的成分是硫化氢。
