Methotrexate is a novel inducer of rat liver and intestinal sulfotransferases.
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 1mg/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.
Maiti
Smarajit
S
264 McElroy Hall, Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA.
Chen
Guangping
G
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D015238:Sulfotransferases / Q000096:biosynthesis*; D015262:Xenobiotics / Q000493:pharmacokinetics
D015262:Xenobiotics; D015238:Sulfotransferases; D008727:Methotrexate