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LEC大鼠遗传性肝炎发展过程中对外源物质的UDP-葡萄糖醛酸基转移酶活性增加。

Increase of UDP-glucuronosyltransferase activities toward xenobiotics during the development of hereditary hepatitis in LEC rats.

作者信息

Yokota H, Ikezoe H, Inaba T, Sanda D, Yuasa A, Kasai N

机构信息

Department of Veterinary Biochemistry, School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan.

出版信息

Biochem Pharmacol. 1994 Mar 15;47(6):1091-3. doi: 10.1016/0006-2952(94)90422-7.

DOI:10.1016/0006-2952(94)90422-7
PMID:8147909
Abstract

UDP-glucuronosyltransferase activities were induced spontaneously during the development of hepatitis in LEC (Long Evans Cinnamon-like coat color) rats. Transition of hepatic microsomal UDP-glucuronosyltransferase activities was observed during the development of the LEC rat, which displayed spontaneous fulminant hepatitis with severe jaundice at about 12-16 weeks after birth. UDP-glucuronosyltransferase activities toward various substrates in 8-week-old LEC and LEA (Long Evans Agouti coat color; control) rats were similar. After 8 weeks of age, the transferase activities of LEA rats towards all substrates tested, except for bilirubin, decreased slightly during the next 24 weeks. In LEC rats, the transferase activities towards serotonin and several phenolic xenobiotics, such as 4-nitrophenol, 1-naphthol and 4-methylumbelliferone, but not 4-hydroxybiphenyl, increased about 2-fold at 16 weeks of age. During the 24 weeks following the first 8 weeks of age, the high level activities towards the xenobiotics continued, with the exception of bilirubin transferase activity which decreased gradually. These results suggest that a form of UDP-glucuronosyltransferase, which catalyzes the glucuronidations of serotonin and these xenobiotics except for 4-hydroxybiphenyl, is induced during the development of hepatitis in the LEC rat.

摘要

在LEC(长 Evans 肉桂色被毛)大鼠肝炎发展过程中,UDP-葡萄糖醛酸基转移酶活性自发诱导产生。在LEC大鼠发育过程中观察到肝微粒体UDP-葡萄糖醛酸基转移酶活性的转变,该大鼠在出生后约12 - 16周时出现自发性暴发性肝炎并伴有严重黄疸。8周龄的LEC大鼠和LEA(长 Evans 刺豚鼠色被毛;对照)大鼠对各种底物的UDP-葡萄糖醛酸基转移酶活性相似。8周龄后,LEA大鼠对除胆红素外的所有测试底物的转移酶活性在接下来的24周内略有下降。在LEC大鼠中,对血清素和几种酚类异生物质(如4-硝基苯酚、1-萘酚和4-甲基伞形酮,但不包括4-羟基联苯)的转移酶活性在16周龄时增加了约2倍。在8周龄后的24周内,除胆红素转移酶活性逐渐下降外,对外源物质的高水平活性持续存在。这些结果表明,在LEC大鼠肝炎发展过程中,一种催化血清素和除4-羟基联苯外的这些外源物质葡萄糖醛酸化的UDP-葡萄糖醛酸基转移酶形式被诱导产生。

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