Abstract | BACKGROUND:
Endothelins have been implicated in gastric mucosal damage in a variety of animal models. Exogenous ET-1 and ET-3 are causally associated with experimental gastric ulcers. Furthermore, clinical reports also show elevated plasma and gastric mucosal endothelin-1 levels in patients suffering from peptic ulcers. AIM: METHODS: Water immersion restrained stress (WIRS) and indomethacin were used to provoke gastric mucosal damage. Endothelin receptor antagonists were administered orally prior to the induction of gastric damage. The gastric lesion index (mm), assessed macroscopically, and myeloperoxidase (MPO) activity were used as markers of the extent of mucosal injury. RESULTS:
Bosentan at 100 and 30 mg/kg administered orally caused attenuation of gastric damage in the WIRS model by 58% and 42%, respectively. Bosentan also caused complete reduction of MPO activity. In indomethacin-induced gastric damage, 100 mg/kg bosentan attenuated gastric damage by 45% and 61% as measured by the gastric lesion index and MPO activity respectively. Ro 48-5695 was at least 30 times more potent than bosentan in reducing indomethacin-induced mucosal damage and at 3 mg/kg, caused a decrease of 49% in the gastric lesion index and a reduction in MPO activity of 41%. Bosentan and Ro 48-5695 possess weak antisecretory properties as tested in the mouse gastric gland assay, than cannot, alone, account for their anti- ulcer properties. CONCLUSIONS:
|
Authors | I Padol, J Q Huang, R H Hunt |
Journal | Alimentary pharmacology & therapeutics
(Aliment Pharmacol Ther)
Vol. 13
Issue 4
Pg. 537-44
(Apr 1999)
ISSN: 0269-2813 [Print] England |
PMID | 10215740
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Anti-Ulcer Agents
- Endothelin Receptor Antagonists
- Ro 48-5695
- Sulfonamides
- Indomethacin
|
Topics |
- Animals
- Anti-Ulcer Agents
(therapeutic use)
- Disease Models, Animal
- Endothelin Receptor Antagonists
- Indomethacin
(pharmacology)
- Male
- Mice
- Rats
- Rats, Wistar
- Stomach Ulcer
(chemically induced, prevention & control)
- Stress, Physiological
(physiopathology)
- Sulfonamides
(therapeutic use)
|