Effects of leminoprazole, omeprazole and sucralfate on indomethacin-induced delayed healing of kissing gastric ulcers in rats.

We have examined whether or not repeated treatment with indomethacin delays the healing of kissing gastric ulcers induced in rats. The effects of leminoprazole, omeprazole and sucralfate on any delay in ulcer healing caused by indomethacin were also determined in relation to myeloperoxidase activity. Kissing gastric ulcers were induced by luminal application of an acetic acid solution. Indomethacin significantly delayed ulcer healing in a dose-dependent manner. Leminoprazole and omeprazole decreased the size and depth of ulcers, the healing of which was delayed by indomethacin, while sucralfate only decreased the ulcer depth. Histological studies showed that indomethacin inhibited tissue contraction and regeneration of the ulcerated mucosa. Leminoprazole and omeprazole prevented the inhibition of these parameters. The myeloperoxidase (MPO) activity of the ulcer portion in animals treated with indomethacin was markedly higher than in the control group. Both leminoprazole and omeprazole, but not sucralfate, significantly reduced MPO activity in contrast to the control value (in the presence of indomethacin). There was a significant relationship between the ulcerated area and myeloperoxidase activity. These results suggested that: (i) leminoprazole and omeprazole prevent the indomethacin-induced delay in ulcer healing by promoting tissue contraction and regeneration of the ulcerated mucosa; (ii) sucralfate prevents the indomethacin-induced delay in ulcer healing via the promotion of the formation of granulation tissue; and (iii) MPO activity will be useful to biochemically ensure the healing state of ulcers.