Role of Acid and Pepsin in Acute Experimental Esophagitis

Goldberg, Henry I.; Dodds, Wylie J.; Gee, Sheldon; Montgomery, Carolyn K.; Zboralske, F. Frank

doi:10.1016/s0016-5085(69)80121-6

Cited by 203 publications

(89 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2,3 The refluxed juice, that is, acid and duodenal components, individually or in combination, contributes to the development of GERD. 4 In animal and patient studies, it is shown that acid, particularly in combination with pepsin, can cause severe damage of the esophageal mucosa, [5][6][7] as in esophagitis and stenosis of Barrett's esophagus. 8 Further investigations of the role of bile reflux in the constellation of GERD give new insights into the development of esophagitis, Barrett's esophagus, and esophageal adenocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

Emerging Concepts of Bile Reflux in the Constellation of Gastroesophageal Reflux Disease

Kauer

Stein

2010

Journal of Gastrointestinal Surgery

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

Emerging Concepts of Bile Reflux in the Constellation of Gastroesophageal Reflux Disease

Kauer

Stein

2010

Journal of Gastrointestinal Surgery

View full text Add to dashboard Cite

show abstract

“…It is assumed that the effect of acid suppressant therapy against reflux esophagitis is accounted for, at least partly, by modification of the proteolytic activity of pepsin. Although there is no evidence for a definite role for pepsin in the pathogenesis of esophagitis (6), experimental evidence shows a pathogenic role for pepsin in the development of acute esophagitis models in rabbits and cats (7,8). Nevertheless, the role of pepsin in the refluxate as an aggressive factor has not been well studied.…”

mentioning

confidence: 99%

Essential Role of Pepsin in Pathogenesis of Acid Reflux Esophagitis in Rats

et al. 2006

View full text Add to dashboard Cite

Pepsin, a protease activated by gastric acid, is a component of the refluxate, yet the role of pepsin in the pathogenesis of reflux esophagitis has not been well studied. In the present study, we examined the effect of pepstatin, a specific inhibitor of pepsin, on acid reflux esophagitis. Acid reflux esophagitis was induced in rats by ligating both the pylorus and the forestomach for 3 or 4 hr. Pepstatin, ecabet Na (the anti-ulcer drug), and L-glutamine were administered intragastrically after the ligation. Pepstatin or ecabet Na, given intragastrically, significantly prevented esophageal lesions, even though they did not affect basal acid secretion in pylorus-ligated rats. Pepstatin significantly inhibited pepsin activity in vivo and in vitro, while ecabet Na inhibited this activity in vitro. By contrast, L-glutamine given intragastrically aggravated the lesions in a dose-dependent manner, but even in the presence of L-glutamine the development of esophageal lesions was totally prevented by coadministration of pepstatin or ecabet Na. L-Glutamine increased the pH of gastric contents to approximately 2.0, the optimal pH for the proteolytic activity of pepsin in vitro. In addition, intragastric administration of exogenous pepsin worsened the severity of esophageal damage. These results suggest that pepstatin is highly effective against acid reflux esophagitis, without influencing acid secretion, while L-glutamine aggravated these lesions by increasing the pepsin activity by shifting the intraluminal pH to the optimal pH range for proteolytic action. It is assumed that pepsin plays a major pathogenic role in the development of acid reflux esophagitis.

show abstract

“…Some studies have showed that various grades of esophagitis and Barrett's esophagus are related to gastroesophageal reflux (Goldberg et al, 1969;DeMeester et al, 1980;Stein et al, 1992). Among the gastric refluxates, acid has been shown to be a potent stimulator to induce COX-2 expression and PGs synthesis (Zhang et al, 2001;Lanas and Santolaria, 2001) which contributes to the development of gastro-esophageal reflux diseases.…”

Section: Discussionmentioning

confidence: 99%

Acid-induced COX-2 expression and prostaglandin E2 production via activation of ERK1/2 and p38 MAPK in cultured feline esophageal smooth muscle cells

et al. 2011

View full text Add to dashboard Cite

Cyclooxygenase (COX)-2 is known to play an important role in inflammatory conditions such as reflux esophagitis resulting from acid reflux. In this study, we tested whether an acidic medium (pH 4.0) induces an increase in COX-2 expression or PGE(2) production, and explored the implication of mitogen-activated protein kinases (MAPKs) activation in these responses in cultured cat esophageal smooth muscle cells. Acidic cytotoxicity was assessed and expression changes in COXs or phosphorylated MAPKs were analyzed by Western blotting. PGE(2) production was measured by immunoassay. No significant decrease in cell viability was observed for 6 h exposure to acidic medium. COX-2 expression and PGE(2) production significantly increased to maximal levels at 6 h exposure to acidic medium. The cells also exhibited significant activation of ERK1/2 and p38 MAPK, but not JNK within 10 min under acidic medium. The increments of COX-2 expression and PGE(2) production by acidic medium were decreased by pretreatment with PD98059 or SB202190, respectively. These results suggest that acidic environments may enhance the COX-2 expression and PGE(2) production through activation of ERK1/2 and p38 MAPK in the cultured cat esophageal smooth muscle cells.

show abstract

Role of Acid and Pepsin in Acute Experimental Esophagitis

Cited by 203 publications

References 13 publications

Emerging Concepts of Bile Reflux in the Constellation of Gastroesophageal Reflux Disease

Emerging Concepts of Bile Reflux in the Constellation of Gastroesophageal Reflux Disease

Essential Role of Pepsin in Pathogenesis of Acid Reflux Esophagitis in Rats

Acid-induced COX-2 expression and prostaglandin E2 production via activation of ERK1/2 and p38 MAPK in cultured feline esophageal smooth muscle cells

Contact Info

Product

Resources

About