Methotrexate is a novel inducer of rat liver and intestinal sulfotransferases

被引：27

作者：

Maiti, S ^{[1
]}

Chen, GP ^{[1
]}

机构：

[1] Oklahoma State Univ, Coll Vet Med, Dept Physiol Sci, Stillwater, OK 74078 USA

来源：

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2003年 / 418卷 / 02期

关键词：

methotrexate; aryl sulfotransferase; hydroxysteroid sulfotransferase; induction; rat liver; rat intestine; regulation;

D O I：

10.1016/j.abb.2003.08.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The antifolate drug methotrexate (MTX) is commonly used in the treatment of different types of cancers and autoimmune diseases. In the present investigation, MTX is shown to be a novel xenobiotic inducer of rat liver and intestinal sulfotransferases (STs). STs are phase II drug metabolizing enzymes. ST induction by hormones and other endogenous molecules has been relatively well studied. Xenobiotic drug induction of STs is not well known. Our enzyme assay, Western blot, and reverse transcription polymerase chain reaction (RT-PCR) results demonstrated that protein and mRNA expressions of aryl sulfotransferase (AST-IV) and hydroxysteroid sulfotransferase (STa) were induced in liver and intestine of male and female rats following MTX treatment at three different doses (0.04, 0.2, and 1 mg/kg/day) for 2 weeks. Intestinal inductions were found to be much greater than those found in liver. MTX is the first antifolate and apoptosis-inducing drug to show induction of STs. (C) 2003 Elsevier Inc. All rights reserved.

引用

页码：161 / 168

页数：8

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