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肠道在四氯化碳排泄中的作用。

The role of the intestinal tract in the elimination of carbon tetrachloride.

作者信息

Page D A, Carlson G P

机构信息

Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907-1334.

出版信息

Toxicol Appl Pharmacol. 1994 Feb;124(2):268-74. doi: 10.1006/taap.1994.1032.

Abstract

The target organ toxicity, mechanisms of toxicity, and metabolism of carbon tetrachloride (CCl4) have been studied extensively. However, there is a paucity of information concerning its elimination. Previous inhalation studies showed that a significant amount of 14C appeared in the feces of rats and monkeys exposed to 14CCl4. The nature of the compound(s) excreted in the feces has not been well characterized. Fecal excretion is a major route of elimination for many lipophilic compounds that are resistant to metabolism. A mechanism of excretion for these compounds is the direct exsorption from the blood to the lumen of the intestinal tract. The primary purpose of this study was to determine if fecal elimination contributes significantly to the elimination of CCl4. The secondary purpose was to determine the mechanism (biliary and/or nonbiliary, i.e., direct exsorption) of fecal elimination of CCl4 and/or its metabolite(s) in Sprague-Dawley rats. The results indicate that both biliary and nonbiliary mechanisms contribute to the fecal elimination of CCl4 following a single iv dose (1 mmol/kg), but this route accounts for less than 1% of the administered dose. The results also indicate that CCl4 is not eliminated unchanged in the feces following either acute treatment (iv or ip) or repeated inhalation exposures. Fecal elimination of CCl4 does not significantly contribute to the overall elimination of CCl4.

摘要

四氯化碳(CCl4)的靶器官毒性、毒性机制及代谢已得到广泛研究。然而,关于其消除的信息却很匮乏。以往的吸入研究表明,暴露于14CCl4的大鼠和猴子粪便中出现了大量的14C。粪便中排泄的化合物的性质尚未得到很好的表征。粪便排泄是许多抗代谢亲脂性化合物的主要消除途径。这些化合物的排泄机制是从血液直接排泌到肠道腔内。本研究的主要目的是确定粪便消除是否对CCl4的消除有显著贡献。次要目的是确定Sprague-Dawley大鼠粪便中CCl4和/或其代谢物的消除机制(胆汁性和/或非胆汁性,即直接排泌)。结果表明,单次静脉注射剂量(1 mmol/kg)后,胆汁性和非胆汁性机制均对CCl4的粪便消除有贡献,但该途径占给药剂量的比例不到1%。结果还表明,无论是急性治疗(静脉注射或腹腔注射)还是反复吸入暴露后,CCl4在粪便中均不会以原形消除。CCl4的粪便消除对CCl4的总体消除没有显著贡献。

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