代谢
GI tract指的是人体的消化道，是人们接触环境化学物质的主要途径。在这项研究中，我们检查了有机锡化合物通过口服给药在小肠上皮细胞中的作用，这是一个对药物和其他化学物质代谢非常活跃的器官。一系列正丁基锡化合物通过灌胃的方式给予雄性Sprague-Dawley大鼠（体重225-275克），单次剂量高达250微摩尔/千克体重。二(三正丁基锡)氧化物以剂量和时间依赖性的方式减少了肠道细胞色素P450的含量和功能活性，同时微囊体血红素加氧酶的活性增加了3倍。二正丁基锡二氯化物对血红素加氧酶和细胞色素P450的影响在小肠中非常明显，并在口服暴露21小时内延伸到肝脏和肾脏，而二(三正丁基锡)氧化物对肝脏的影响要晚得多（6天后），此时细胞色素P450的含量显著减少了30%。此外，四正丁基锡在24小时内对细胞色素P450的影响局限于肠上皮细胞。这些研究表明有机锡化合物在肠道中具有重要的药理作用，并提示口服摄入有机锡与其他环境污染物可能会改变小肠中细胞色素P450依赖性的外源化学物质和该单加氧酶系统的天然底物的代谢。
The GI tract is a major route by which humans are exposed to environmental chemicals. We have examined in these studies the effects of oral admin of organotin cmpds in the small intestinal epithelium, an organ which exhibits highly active drug & other chemical metab. A series of n-butyltin cmpds was admin by gavage to male Sprague-Dawley rats (225-275g) in single doses up to to 250 umol/kg bw. Bis(tri-n-butyltin)oxide produced dose & time dependent decr in the content & functional activity of intestinal cytochrome p450, together with an elevation (3-fold) in the activity of microsomal heme oxygenase. The effects of di-n-butyltin dichloride on heme oxygenase & cytochrome p450 were pronounced in the small intestine & extended to the liver & kidneys within 21hr after oral exposure, whereas bis(tri-n-butyltin)oxide did not affect the liver until much later (6 days), when cytochrome p450 content was reduced markedly (30%). Furthermore, the effects produced by tetra-n-butyltin on cytochrome p450 at 24hr were localized in the intestinal epithelium. These studies indicate important pharmacological effects of organotin cmpd in the gut, & raise the possibility that concurrent oral ingestion of organotins with other environmental pollutants may alter the cytochrome p450 dependent metab of xenobiotics & natural substrates of this monooxygenase system in the small intestine.
来源:Hazardous Substances Data Bank (HSDB)
