Ketotifen is protective against indomethacin-induced intestinal ulceration in the rat.
Ketotifen is an anti-allergic agent that was recently shown to prevent experimental gastric and colonic mucosal injury. We studied the effect of ketotifen on indomethacin-induced small intestinal ulceration in the rat. Ulceration was produced by s.c. injection of 30 mg/kg indomethacin, 30 min after refeeding 24 h fasted rats. Total ulcer area (mm2), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were measured 24 h after indomethacin administration. Study groups received ketotifen 100 micrograms/ 100 g body weight 30 min before and 5 h after indomethacin administration, either i.p. or orally. There were 7-9 animals in each group. Ulcer area was significantly reduced by oral administration of ketotifen from 229 +/- 26 to 146 +/- 28 mm2. PGE2 level was reduced by ketotifen from 505 +/- 73 to 228 +/- 68 ng/mg protein, and LTB4 was reduced from 289 +/- 68 to 59 +/- 26 ng/mg protein. Intraperitoneal administration of ketotifen had no effect on any of the measured parameters. Ketotifen had a definite protective effect on small intestinal mucosa in the rat, which was accompanied by a reduction of mucosal inflammatory mediators. Ketotifen may have a role in the prevention or treatment of small intestinal damage induced by nonsteroidal anti-inflammatory drugs.
Zahavi
I
I
Division of Pediatric Gastroenterology and Nutrition, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Weizen
T
T
Marcus
H
H
Karmeli
F
F
Dinari
G
G
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D015232:Dinoprostone / Q000032:analysis; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004381:Duodenal Ulcer / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D007213:Indomethacin / Q000009:adverse effects*; D007665:Ketotifen / Q000627:therapeutic use*; D007975:Leukotriene B4 / Q000032:analysis; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006634:Histamine H1 Antagonists; D007975:Leukotriene B4; D015232:Dinoprostone; D007665:Ketotifen; D007213:Indomethacin