Prevention by aluminium phosphate of gastric lesions induced by ethanol in the rat: role of endogenous prostaglandins and sulfhydryls.
This study was designed to demonstrate the cytoprotective effect of an antacid containing aluminium phosphate (Phosphalugel) against ethanol-induced gastric injury in the rat and to determine whether this cytoprotective effect is mediated by endogenous prostaglandins and sulfhydryls. We have quantitatively evaluated gastric mucosal lesions using macroscopic and histological techniques one hour after ethanol administration. Two ml of aluminium phosphate given orally one hour before administration of 2 ml of 100% ethanol significantly (p less than 0.01) reduced the area of macroscopic lesions induced by ethanol (3.3 +/- 0.9%) when compared to distilled water (20 +/- 4.8%). The histological study showed that aluminium phosphate prevented deep tissue necrosis. However, it did not protect surface epithelial cells against ethanol injury. Pretreatment with indomethacin, 5 mg/kg sc one hour before aluminium phosphate, slightly but significantly (p less than 0.05) reduced the cytoprotective effect of aluminium phosphate. Macroscopic lesions occupied 4.3 +/- 0.94% and 1.88 +/- 0.41% of total mucosal area in indomethacin group and in vehicle group, respectively. On the other hand, the sulfhydryl blocker, N-ethyl-maleimide, 10 mg/kg sc, given one hour before aluminium phosphate, completely abolished the cytoprotective effect of aluminium phosphate (32.92 +/- 4.85% in N-ethyl-maleimide group versus 3.78 +/- 1.41% in vehicle group; p less than 0.01). These results show that aluminium phosphate has a cytoprotective effect against ethanol injury in the rat. This property appears to be mediated by both endogenous prostaglandins and sulfhydryls.
Duchateau
A
A
Laboratory of Cellular Digestive Morphology, University of Medicine, Reims, France.
Thiefin
G
G
Varin-Bischoff
S
S
Garbe
E
E
Zeitoun
P
P
D000535:Aluminum / Q000494:pharmacology*; D017607:Aluminum Compounds; D000818:Animals; D000863:Antacids / Q000494:pharmacology; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005033:Ethylmaleimide / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010710:Phosphates / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000378:metabolism
D017607:Aluminum Compounds; D000863:Antacids; D010710:Phosphates; D011453:Prostaglandins; D013438:Sulfhydryl Compounds; D000431:Ethanol; D000535:Aluminum; C012714:aluminum phosphate; D005033:Ethylmaleimide; D007213:Indomethacin