Correlation between methotrexate-induced intestinal damage and decrease in polyamine content.
A synthetic analog of prostaglandin E(1), OP-1206 [17S, 20-dimethyl-trans-Delta(2)-prostaglandin E(1)] protects the small intestine from the methotrexate (MTX)-induced damage. The purpose of this study is to evaluate the protective effect of OP-1206 on the methotrexate-induced small intestinal damage in rats from the biochemical point of view. MTX (15 mg/kg body weight) was orally administered to rats once daily for 5 days. OP-1206 (0.5 microg/kg body weight) was orally administered to rats twice a day for 5 days, and on the 6th day biochemical components in the jejunal mucosa of the treated rats were determined. The contents of DNA, RNA, proteins and polyamines (spermine and spermidine) in the jejunal mucosa of rats were markedly decreased by the MTX treatment. The coadministration of OP-1206 with MTX prevented such decreases caused by the MTX treatment. The MTX treatment decreased the incorporation of 3H-thymidine into DNA in the jejunal mucosa, while the coadministration of OP-1206 with MTX prevented it. These results indicated that OP-1206 could protect the intestinal mucosa against the biochemical effects of MTX through a trophic action on intestinal villi. Further, it should be noted that polyamines may possibly play an important role of modulation action on intestinal mucosa.
Gao
Feng
F
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Japan.
Tomitori
Hideyuki
H
Igarashi
Kazuei
K
Horie
Toshiharu
T
D000284:Administration, Oral; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis; D004359:Drug Therapy, Combination; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000633:toxicity*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D012313:RNA / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D011459:Prostaglandins E, Synthetic; D013096:Spermine; D012313:RNA; C025090:ONO 1206; D004247:DNA; D000527:Alprostadil; D008727:Methotrexate