期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 418, 期 2, 页码 161-168出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.abb.2003.08.019
关键词
methotrexate; aryl sulfotransferase; hydroxysteroid sulfotransferase; induction; rat liver; rat intestine; regulation
资金
- NIGMS NIH HHS [GM59873] Funding Source: Medline
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.
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