Is the ex vivo rat gastric chamber model suitable for studying the gastrotoxicity of refluxed duodenal contents? Initial results using deoxycholic acid.
Duodenogastric reflux has been implicated in the pathogenesis of gastric mucosal disease but the relative toxicities of its constituents are not known. The suitability of the ex vivo rat gastric chamber model for systematic studies of bile acid gastrotoxicity was assessed using deoxycholic acid (DCA 0.2-5.0 mmol/l). Acute challenge with 5.0 mmol/l DCA produced significant loss of gastric transmucosal potential difference (delta PD = 25.9 +/- 3.3 mV: mean +/- SEM; p less than 0.01) compared with saline challenge (1.5 +/- 0.5 mV). Significant delta PD values were produced by DCA concentrations down to 0.5 mmol/l (16.0 +/- 2.8 mV). Challenge with 5.0 mmol/l DCA also caused significant increases in chamber fluid concentrations of nucleic acid (2.8 +/- 0.3 micrograms/ml; p less than 0.05) and acid phosphatase (130 +/- 23.4 microU/ml; p less than 0.01). This study demonstrates DCA gastrotoxicity at concentrations comparable to human intragastric total bile acid concentrations and the suitability of this model for studying the toxic components of refluxed duodenal contents.
Armstrong
D
D
Gastroenterology Unit, UMDS of Guy's Hospital, London, UK.
Farrell
M
M
Hanby
A
A
Murphy
G M
GM
Dowling
R H
RH
D000818:Animals; D003840:Deoxycholic Acid / Q000009:adverse effects*; D004383:Duodenogastric Reflux / Q000503:physiopathology*; D004563:Electrochemistry; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008297:Male; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains
D003840:Deoxycholic Acid