Adaptive cytoprotection of gastric surface epithelial cells against injury by physiologic concentrations of bile acid.
The purpose of this study was to determine whether adaptive cytoprotection of gastric mucosa could be demonstrated with concentrations of bile acid, which is normally found in the human stomach, and whether cyclooxygenase inhibition, in turn, could blunt the response. Surface epithelial cell exfoliation and ion fluxes were used as end points. A transduodenal gastric cannula was placed, and the pylorus/gastroesophageal junction was ligated in adult male Sprague-Dawley rats that had been anesthetized. In experiment 1 (N = 30), rat stomachs were exposed for 15 minutes to 5 ml of either a neutral test solution (160 mmol/L NaCl, pH 7) or 1 mmol/L acidified taurocholate (ATC) (100 mmol/L HCl, 60 mmol/L NaCl, 1 mmol/L taurocholic acid; pH 1.2). All rats were subsequently exposed for 15 minutes to 5 mmol/L ATC during which time mucosal injury was assessed by measuring net flux of H+, Na+, and K+, volume, and DNA efflux. In experiment 2 (N = 35), all stomachs were pretreated for 15 minutes with 1 mmol/L ATC before mucosal injury with 5 mmol/L ATC (15 minutes). Eighteen rats were pretreated with indomethacin (5 mg/kg) subcutaneously 75 minutes before the experiment was begun, and the same parameters were measured. Pretreatment of rat gastric mucosa with 1 mmol/L ATC significantly attenuated the mucosal injury that was seen with subsequent exposure to 5 mmol/L ATC, resulting in significantly (p less than 0.05) less luminal H+ loss (-16 +/- 4 vs -32 +/- 4 mEq/15 min) and DNA efflux (181 +/- 21 vs 270 +/- 25 micrograms/15 min) than the nonadapted group. Indomethacin pretreatment significantly attenuated the adaptive protective response, resulting in greater loss of H+ (-29 +/- 4 vs -18 +/- 3) and DNA efflux (190 +/- 35 vs 110 +/- 18, both p less than 0.05) after exposure to 5 mmol/L ATC. These studies demonstrate that adaptive cytoprotection of gastric mucosa occurs with physiologic concentrations of an irritant that is normally present in the stomach. Indomethacin blunts this effect, which suggests that adaptive cytoprotection in this setting may be mediated by production of endogenous prostaglandins.
Dempsey
D T
DT
Reichle Research Laboratory, Department of Surgery, Temple University, Philadelphia, Pa.
Mercer
D W
DW
Deb
B
B
Sauter
A
A
Ritchie
W P
WP
D000143:Acids; D000222:Adaptation, Physiological; D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology*; D005753:Gastric Mucosa / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000494:pharmacology
D000143:Acids; D001647:Bile Acids and Salts; D013656:Taurocholic Acid; D007213:Indomethacin