Cimetidine reduces bile acid-mediated small intestinal mucosal injury in rats in vivo.
Whether cimetidine has protective effects on the gastrointestinal mucosa independent of its ability to reduce gastric acid secretion is still controversial. To study this, rats had small intestinal mucosal injury induced in vivo by perfusion with 5 mM chenodeoxycholic acid. Control rats were compared to rats receiving either intraperitoneal or intravenous pretreatment with 50 mg/kg cimetidine or intraluminal pretreatment with 0.5 mM cimetidine. Mucosal injury was assessed by measuring villus tip epithelial cell denudation by computerized quantitative morphology. Intraperitoneal cimetidine reduced the average denudation/villus (micrometers) caused by 45-min perfusion with chenodeoxycholic acid: control = 39.1 +/- 7.7 (SEM), intraperitoneal cimetidine = 20.8 +/- 3.5 (P less than 0.05). Additionally, both intraluminal and intravenous cimetidine reduced villus denudation caused from 30 min perfusion with chenodeoxycholic acid: control = 62.5 +/- 5.8, intravenous cimetidine = 42.6 +/- 4.7 (P less than 0.05), intraluminal cimetidine = 44.6 +/- 7.2 (P less than 0.05). The observation that reduced mucosal injury is observed in an in vivo model that is independent of gastric acid supports the conclusion that cimetidine indeed has acid-independent protective properties.
Erickson
R A
RA
Department of Medicine, Veterans Administration Medical Center, Long Beach, California 90822.
D000818:Animals; D002635:Chenodeoxycholic Acid / Q000633:toxicity*; D002927:Cimetidine / Q000008:administration & dosage / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects; D008297:Male; D010477:Perfusion; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002635:Chenodeoxycholic Acid; D002927:Cimetidine