The influence of leukotriene receptors' antagonists on experimentally induced ulcer in rats.

AIM

Gastric mucosal cells synthesize a large number of eicosanoids (including leukotrienes) which are distinctively involved in ulcerogenesis. This experimental study investigated the effect of 4 leukotriene receptors' antagonists on indomethacin(IND)-induced ulcer in rats.

MATERIAL AND METHODS

Animals were divided into six groups (of 8 rats each) which received as follows: group I (control)--saline; group II--IND 20 mg/kg p.o.; group III--montelukast sodium 10 mg/kg p.o. and IND 20 mg/kg p.o.; group IV-- a quinolinic derivative (19363) 20 rM/kg p.o. and IND 20 mg/kg p.o.; group V--a phenethylamido derivative (20599) 20 microM/kg p.o. and IND 20 mg/ kg p.o.; group VI--a resatophenone derivative (19072) 20 microM/kg p.o. and IND 20 mg/kg p.o. Animals were sacrificed eight hours after the last administration. The gastric index (UI), gastric pH and histopathological exam were performed on the removed stomachs.

RESULTS

UI was 25.8 +/- 6.3 in group II, 10.20 +/- 2.3 in group III (p < 0.05), 21.60 +/- 2.8 in group IV, 13.40 +/- 2.4 in group V (p < 0.05) and 20.80 +/- 3.9 in group VI. pH values were 2.2 +/- 0.3 in group II, 3.4 +/- 0.9 in group III (p < 0.05), 2.6 +/- 0.8 in group IV, 2.9 +/- 0.7 in group V and 2.5 +/- 0.6 in group VI. The histopathological exam revealed: (i) typical lesions for ulcer in groups II, IV and VI, the most severe being in group II; (ii) only superficial non-hemorrhagic erosions in group V; (iii) small erosion areas alternating with large zones of normal mucosa in group III. The obtained data demonstrated different degrees of gastro-protective activity for the studied leukotriene receptor antagonists.

CONCLUSION

Especially montelukast but also phenethylamido derivative (20599) exhibited a partial gastro-protective effect on IND-induced ulcer in rats.