Clinica Chimica Acta, 178 (1988) 313-326 Elsevier 313 CCA 04323 Is the ex vivo rat gastric chamber model suitable for studying the gastrotoxicity of refluxed duodenal contents? Initial results using deoxycholic acid D. Armstrong, M. Farrell, A. Hanby, G.M. Murphy and R.H. Dowling Gastroenrerology Unit, UMDS of Guy’s and St Thomas’ Hospitals, London (UK) (Received 26 April 1988; revision received 29 August 1988; accepted after revision 24 September 1988) Key worak Gastrotoxicity; Duodenogastric reflux; Rat; Deoxycholic acid; Gastric; Stomach; Bile acid zyxwvutsrqpo Summary 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 gastrotoxic- ity 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 (APD = 25.9 f 3.3 mV: mean f SEM; p < 0.01) compared with saline challenge (1.5 f 0.5 mV). Significant APD values were produced by DCA con- centrations down to 0.5 mmol/l (16.0 it 2.8 mV). Challenge with 5.0 mmol/l DCA also caused significant increases in chamber fluid concentrations of nucleic acid (2.8 f 0.3 pg/ml; p < 0.05) and acid phosphatase (130 f 23.4 /.~U/rnl; p < 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. Introduction Duodenogastric reflux has been implicated in the pathogenesis of a variety of gastric mucosal diseases ranging from gastritis [l], with or without associated dyspeptic symptoms [2,3], through benign gastric ulceration [4], to intestinal metap- lasia and epithelial dysplasia - possible precursors of frank gastric carcinoma [5]. Refluxed duodenal juice contains a number of potentially gastrotoxic substances, Correspondence to: D. Armstrong, Gastroenterology Unit, Guy’s Campus, UMDS of Guy’s and St Thomas’ Hospital, St Thomas’ Street, London SE1 9RT, UK. 0009-8981/88/$03.50 6 1988 Elsevier Science Publishers B.V. (Biomedical Division)