Effect of a synthetic analog of prostaglandin E1 on the intestinal mucosa of methotrexate-treated rats.
Administration of methotrexate to rats sometimes induces small intestinal damage. A synthetic analog of prostaglandin E1, OP-1206 [17S,20-dimethyl-trans-delta2-prostaglandin E1] may possibly provide therapeutic benefits to help recovery from such small intestinal damage. The purpose of this study was to evaluate the effect of OP-1206 on methotrexate-induced small intestinal damage in rats. Methotrexate (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 the small intestine of the rats were examined histologically and biochemically. The methotrexate treatment of rats caused a severe histological change in the small intestinal mucosa, whereas the treatment combined of OP-1206 with methotrexate showed similar histological features of the small intestinal mucosa as that of the control rats. On the other hand, an acute intestinal inflammation was evaluated by determining myeloperoxidase activity. The myeloperoxidase activity in the small intestinal mucosa of the methotrexate-treated rats increased remarkably, whereas that of the methotrexate and OP-1206-treated rats was significantly lower than that of the methotrexate-treated rats. Thus, it was shown histologically and biochemically that OP-1206 was effective in protecting the small intestine from methotrexate-induced damage.
Gao
F
F
Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Ueda
S
S
Horie
T
T
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology; D007249:Inflammation; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; D005343:Fibrinolytic Agents; D011459:Prostaglandins E, Synthetic; D014665:Vasodilator Agents; C025090:ONO 1206; D009195:Peroxidase; D000527:Alprostadil; D008727:Methotrexate