Gao Feng, Tomitori Hideyuki, Igarashi Kazuei, Horie Toshiharu
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Japan.
Life Sci. 2002 Dec 27;72(6):669-76. doi: 10.1016/s0024-3205(02)02241-5.
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.
前列腺素E(1)的合成类似物OP-1206 [17S, 20-二甲基-反式-Δ(2)-前列腺素E(1)]可保护小肠免受甲氨蝶呤(MTX)诱导的损伤。本研究的目的是从生化角度评估OP-1206对MTX诱导的大鼠小肠损伤的保护作用。将MTX(15 mg/kg体重)每日一次口服给予大鼠，持续5天。将OP-1206(0.5 μg/kg体重)每日两次口服给予大鼠，持续5天，并在第6天测定处理后大鼠空肠黏膜中的生化成分。MTX处理使大鼠空肠黏膜中的DNA、RNA、蛋白质和多胺(精胺和亚精胺)含量显著降低。OP-1206与MTX共同给药可防止MTX处理引起的这种降低。MTX处理降低了3H-胸腺嘧啶核苷掺入空肠黏膜DNA中的量，而OP-1206与MTX共同给药可防止这种情况。这些结果表明，OP-1206可通过对肠绒毛的营养作用保护肠黏膜免受MTX的生化影响。此外，应注意多胺可能在调节肠黏膜方面发挥重要作用。
