A prostaglandin E1 analog, OP-1206, alleviates 5-fluorouracil-induced injury of rat small intestine.
5-Fluorouracil (5-FU) often causes the gastrointestinal toxicity, including enterocolitis. We investigated effects of OP-1206 (17S, 20-dimethyl-trans-delta2-prostaglandin E1) on 5-FU-induced leukocyte infiltration and epithelial barrier dysfunction of rat small intestine. Myeloperoxidase (MPO) activity of the small intestine was assayed as an index of leukocyte infiltration. Intestinal epithelial permeability was determined by the small intestinal absorption of a paracellular permeation marker, fluorescein isothiocyanate-labeled dextran (molecular weight; 4,400) (FD-4) using the in situ closed intestinal loop technique. The MPO activity and FD-4 permeation were significantly increased by the administration of 5-FU to rats for 4 days, while on the coadministration of 5-FU and OP-1206, they were similar to those of control rats treated with saline solution alone, respectively. These observations indicate that OP-1206 reduced the leukocyte infiltration and the change in epithelial permeability of rat small intestine induced by 5-FU.
Hirata
K
K
Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Horie
T
T
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D003911:Dextrans / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005472:Fluorouracil / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000201:enzymology / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D008297:Male; D010539:Permeability; D009195:Peroxidase / Q000378:metabolism; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000964:Antimetabolites, Antineoplastic; D003911:Dextrans; D005456:Fluorescent Dyes; D011459:Prostaglandins E, Synthetic; C025090:ONO 1206; D009195:Peroxidase; D000527:Alprostadil; D016650:Fluorescein-5-isothiocyanate; D005472:Fluorouracil