Effects of sulfhydryl-related compounds on indomethacin-induced gastric lesions in rats: role of endogenous sulfhydryls in the pathogenesis.
The role of mucosal sulfhydryl (SH) in the pathogenesis of indomethacin-induced gastric lesions was investigated in rats. Indomethacin (25 mg/kg, s.c.) caused high-amplitude gastric contractions, resulting in linear hemorrhagic lesions in the corpus mucosa within 4 hr, but did not induce any changes in the mucosal SH levels. These lesions were prevented significantly by prior s.c. administration of cysteamine, glutathione (GSH) or diethylmaleate (DEM), irrespective of whether the mucosal SH was increased by the former two agents or reduced by the latter. N-Ethylmaleimide (NEM) tended to worsen such lesions without any effect on the mucosal SH contents. Gastric hypermotility caused by indomethacin was inhibited significantly by DEM, cysteamine and GSH, while acid secretion was reduced by DEM and NEM. Both cysteamine and GSH prevented the indomethacin-induced linear lesions even in the stomach perfused with 150 mM HCl, whereas in the animals treated with DEM, nonlinear damage was induced exclusively in the antrum by indomethacin in the presence of acid. We conclude that the mucosal SH has no relation to the ulcerogenicity of indomethacin in the gastric corpus mucosa.
Ueshima
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Takeuchi
K
K
Okabe
S
S
D000818:Animals; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000737:chemistry; D007213:Indomethacin / Q000008:administration & dosage; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000502:physiology; D013276:Stomach Ulcer / Q000139:chemically induced*; D013438:Sulfhydryl Compounds / Q000032:analysis / Q000502:physiology*
D013438:Sulfhydryl Compounds; D007213:Indomethacin