Volume 127, Issue 9 pp. 2009-2019
Carcinogenesis

Exogenous luminal nitric oxide exposure accelerates columnar transformation of rat esophagus

Hiroyuki Endo

Hiroyuki Endo

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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Katsunori Iijima

Corresponding Author

Katsunori Iijima

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

Tel.: 81-22-717-7171, Fax: +81-22-717-7177

Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1Seiryo-machi, Aobaku, Sendai 980-8574, JapanSearch for more papers by this author
Kiyotaka Asanuma

Kiyotaka Asanuma

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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Nobuyuki Ara

Nobuyuki Ara

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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Hirotaka Ito

Hirotaka Ito

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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Naoki Asano

Naoki Asano

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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Kaname Uno

Kaname Uno

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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Tomoyuki Koike

Tomoyuki Koike

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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Akira Imatani

Akira Imatani

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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Tooru Shimosegawa

Tooru Shimosegawa

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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First published: 26 August 2010
Citations: 21

Abstract

Exposure of the esophageal mucosa to refluxed gastroduodenal contents is recognized to be an important risk factor for Barrett's esophagus (BE). At the human gastroesophageal junction, nitric oxide is generated luminally through the enterosalivary recirculation of dietary nitrate, and in cases with gastroesophageal reflux, the site of luminal nitric oxide generation could shift to the distal esophagus. The aim of this study is to investigate whether exogenous luminal nitric oxide could promote the development of BE in rats. Sodium nitrite plus ascorbic acid were administered to a rat surgical model of BE, in which the gastroduodenal contents were refluxed into the esophagus to generate exogenous luminal nitric oxide in the esophagus by the acid-catalyzed chemical reaction between the 2 reagents. The emergence of BE was evaluated histologically in the early phase (several weeks) after the surgery with or without exogenous nitric oxide administration. To elucidate the histogenesis of BE, CDX2, MUC2 and MUC6 expressions were investigated immunohistochemically. Coadministration of sodium nitrite plus ascorbic acid significantly accelerated the timing of emergence and increased the area of BE compared with controls. Administration of either reagent alone did not show any promotive effects on BE formation. Immunohistochemically, the columnar epithelium thus induced was similar to the specialized intestinal metaplasia in human BE. The results of this animal model study suggest that exogenous luminal nitric oxide could be involved in the pathogenesis of the columnar transformation of the esophagus. Further studies in human are warranted.

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