Gastric mucosal toxicity of duodenal juice constituents in the rat. Acute studies using ex vivo rat gastric chamber model.
To determine the acute gastrotoxicity of refluxed duodenal contents, an ex vivo rat gastric chamber was used to study mucosal damage produced by conjugated and unconjugated human bile acids and lysolecithin at neutral and acidic pH; the effects of trypsin, human duodenal aspirate, and combinations of chenodeoxycholic acid, lecithin, and lysolecithin were also studied. At neutral pH, all bile acids except tauroursodeoxycholic acid, caused dose-dependent falls in mucosal potential difference and losses of mucosal nucleic acid into the chamber fluid, indicating mucosal damage. The di-alpha-hydroxy bile acids, deoxycholic and chenodeoxycholic acids, were more gastrotoxic than cholic and ursodeoxycholic acids, and all unconjugated bile acids were more toxic than their conjugated species, none of which produced damage at concentrations below 2.0 mM. For all but the taurine conjugates, bile acid-induced changes in potential difference were lower at acidic then at neutral pH. Lysolecithin gastrotoxicity, comparable at neutral pH to that of chenodeoxycholic acid, was also reduced at acidic pH. Lecithin decreased the gastrotoxicity of chenodeoxycholic acid and lysolecithin. Trypsin produced no damage, and the gastrotoxicity of human duodenal aspirate was unaffected by prior heat inactivation of pancreatic enzymes.
Armstrong
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D
Gastroenterology Unit, UMDS of Guy's Hospital, London, UK.
Rytina
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ER
Murphy
G M
GM
Dowling
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RH
D000704:Analysis of Variance; D000818:Animals; D001647:Bile Acids and Salts / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007419:Intestinal Secretions / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D001647:Bile Acids and Salts