当前位置： SCI文献检索 > TOXICOLOGY AND APPLIED PHARMACOLOGY期刊下所有文献 > Biliary excretion and enterohepatic circulation of 2,4-dinitrotoluene metabolites in Fischer-344 rats.

Biliary excretion and enterohepatic circulation of 2,4-dinitrotoluene metabolites in Fischer-344 rats.

Abstract：

:Technical grade dinitrotoluene (DNT) is hepatocarcinogenic when fed to rats. DNT is oxidatively metabolized by hepatic enzymes and reductively metabolized by rat intestinal microflora in vitro. The objectives of the present studies were to determine the importance of bile as a route of excretion for DNT metabolites and to investigate the role of enterohepatic circulation in the metabolism of DNT. The common bile ducts of male and female F-344 rats were cannulated with an uninterrupted cannula at the hepatic and ileal ends. After 24 hr, male rats were given a po dose of 35, 63, or 100 mg 2,4-[14C]DNT/kg; female rats received 35 mg 2,4-[14C]DNT/kg. Immediately prior to dosing, the cannula was snipped and bile was allowed to collect in a glass reservoir, surgically implanted in the peritoneal cavity, which could be sampled externally. In males, excretion of 14C in bile was linearly related to dose. From 9.2 to 29.2 mumol eq of [14C]DNT (approximately 25% of the dose) appeared in bile within 24 hr. Females dosed with 35 mg/kg excreted only 18% of the dose in the bile. Over 90% of the radioactivity in the bile was the glucuronide conjugate of 2,4-dinitrobenzyl alcohol (DNBAlc-G). In comparison to control rats, in which bile flow to the small intestine was uninterrupted, collection of bile decreased the amount of 14C excreted in urine. In both males and females most of the 2,4-DNT dose excreted in the urine was in the form of the oxidized metabolites DNBAlc-G and 2,4-dinitrobenzoic acid. These results indicate that bile is an important route of excretion for 2,4-DNT metabolites and that metabolites excreted in the bile can be reabsorbed from the gut.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Medinsky MA,Dent JG

doi

10.1016/0041-008x(83)90279-x

subject

Has Abstract

pub_date

1983-05-01 00:00:00

pages

359-66

issue

3

eissn

0041-008X

issn

1096-0333

journal_volume

68

pub_type

杂志文章

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