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 μg/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 tile prevention or treatment of small intestinal damage induced by nonsteroidal anti-inflammatory drugs.