Protective effect of prostaglandins on the methotrexate induced damage of small intestine in rats.
Methotrexate (MTX) treatment causes the damage of the small intestine, resulting in malabsorption. The aim of this study was to investigate the effect of prostaglandins (PGs), prostaglandin E1 (PGE1) and prostaglandin I2 (PGI2) analogues, on the MTX-induced damage of rat small intestine by examining the permeability of the small intestinal epithelium. The rats were treated as follows: MTX (15 mg/kg/day), MTX and PGE1/PGI2 analogues (0.5 and 5 micrograms/kg/twice a day), PGE1/PGI2 analogues alone, and sterile saline (control). All drugs were given orally for 5 days. The intestinal permeability of fluorescein isothiocyanate labeled dextran with average molecular mass 4.4 KDa (FD-4) was examined to evaluate the dysfunction of the small intestine by the in vitro everted small intestine technique. The permeation clearance of FD-4 obtained from the in vitro experiment of the MTX-treated rats increased remarkably, but that of the MTX and PGE1/PGI2 analogue-treated rats was significantly lower than that of the MTX-treated rats. These results indicated that PGE1 or PGI2 analogues possibly alleviated the MTX-induced damage of the small intestine of rats.
Gao
F
F
Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Horie
T
T
D000527:Alprostadil / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000737:chemistry / Q000627:therapeutic use*; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects* / Q000503:physiopathology; D008286:Malabsorption Syndromes / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D011464:Epoprostenol; D000527:Alprostadil; D008727:Methotrexate