Importance of the stress response in acid-induced mucosal injury in opossum esophagus

Abstract

Recent studies suggest that oxidative stress occurs during the development of reflux esophagitis. Changes in heat shock protein (HSP) expression have been observed in patients and in animal models of gastrointestinal disease, although the esophagus has largely been ignored. Aim: To study changes in antioxidant enzyme levels and HSP expression following the induction of esophegitis and after one week of recovery in anesthetized opossums. Methods: The esophagus was pertused intraluminally for 45 minutes on each of 3 consecutive days with either 0.9% saline (NS) (n = 6; control) or 100 mM HCI (n = 6). 24 hours later, the esophagus was excised and samples were removed from distal, middle and proximal sites (1-3, 5-7 and 9-11 cm above the LES, respectively). An additional group of recovery animals (n = 4) was also perfused repeatedly with acid, but was then allowed 7 days to recover prior to tissue removal. Myeloperoxidase (MPO) activity (index of naatrophil accumulation) and mucocal levels of the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were determined spectrophotomatrically for each sample, while mucocal HSP 60, 72 and 90 were examined using western blot. Results: Repeated acid exposure caused significant increases in MPO activity (p<O.O01, p<O.O01, p<O.01), GPx levels (p<O.OB, p<O.O01, p<O.O01) and HSP 90 (p<O.05, p<O.O01, p<O.01) at all 3 sites, compared to controls (p values listed for distal, middle and proximal sites, respectively). No changes in SOD or CAT were found at any site. HSP 72 was found to be significantly decreased (p<O.01, p<O.01) at the distal and middle sites after acid, but no change occurred at the proximal site. HSP 60 content was significantly increased (p<O.05) at the proximal site only. In recovery animals, MPO activity, antioxidant enzyme levels and HSP content were not different from controls at any site. Conclusions: Repeated intraluminal acid exposure induces marked esophageal inflammation that is accompanied by oxidative stress and differential changes in HSP expression, all of which are relatively short-lived it no further exposure occurs. It is not known if the changes in antioxidant status and HSP expression are related. Similar stress responses may also occur in patients chronically challenged with refluxed gastric contents and could play a role in the pathogenesis of gastroesophageal reflux disease.