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百菌清在无菌和常规大鼠体内的离体胃肠道生物转化

Ex vivo gastrointestinal biotransformation of chlorothalonil in the germ-free and conventional rat.

作者信息

Hillenweck A, Corpet D E, Killeen J C, Bliss M, Cravedi J P

机构信息

Laboratoire des Xénobiotiques, INRA, Toulouse, France.

出版信息

Xenobiotica. 1998 Nov;28(11):1017-28. doi: 10.1080/004982598238912.

DOI:10.1080/004982598238912
PMID:9879634
Abstract
  1. The metabolism and absorption of chlorothalonil and corresponding diglutathione and dicysteine conjugates was studied using isolated everted gastrointestinal sacs of the conventional and germ-free rat. An HPLC method was used to analyse mucosal and serosal fluids. Thiol metabolites of chlorothalonil were determined by GC/MS. 2. Low absorption of the substrates was observed, with < 4% of the radioactivity being recovered from the serosal buffers and the digestive tissues. A major part of the radioactivity was recovered from the mucosal fluids and it corresponded to unchanged chlorothalonil. Traces of unchanged chlorothalonil and mono-, di- and trimethylthio metabolites were present in serosal fluids as well as unidentified polar peaks. An important transformation (> 75%) of the chlorothalonil conjugates was observed. The di- and trimethylthio metabolites of chlorothalonil were detected from both sides of the everted gut sac of rat incubated with the diglutathione and dicysteine conjugates. 3. Few differences were observed between the conventional and germ-free rat: absorption was higher in the duodenum of germ-free rat, but tissue retention was more significant in the duodenum of the conventional rat.
摘要
  1. 使用常规大鼠和无菌大鼠的离体翻转胃肠囊研究了百菌清及其相应的二谷胱甘肽和二半胱氨酸共轭物的代谢和吸收。采用高效液相色谱法分析粘膜和浆膜液。百菌清的硫醇代谢物通过气相色谱/质谱法测定。2. 观察到底物的吸收较低,从浆膜缓冲液和消化组织中回收的放射性不到4%。大部分放射性从粘膜液中回收,且与未变化的百菌清相对应。浆膜液中存在痕量未变化的百菌清以及单甲基硫、二甲基硫和三甲基硫代谢物以及未鉴定的极性峰。观察到百菌清共轭物发生了重要转化(>75%)。在用二谷胱甘肽和二半胱氨酸共轭物孵育的大鼠翻转肠囊两侧均检测到百菌清的二甲基硫和三甲基硫代谢物。3. 在常规大鼠和无菌大鼠之间观察到的差异很少:无菌大鼠十二指肠的吸收较高,但常规大鼠十二指肠中的组织滞留更显著。

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