J Korean Med Sci.  2005 Feb;20(1):56-60. 10.3346/jkms.2005.20.1.56.

Expression of Inducible Nitric Oxide Synthase Is Increased in Rat Barrett's Esophagus Induced by Duodenal Contents Reflux

• Bae JD
• Jung KH
• Ahn WS
• Bae SH
• Jang TJ

• KMID: 1781725
• DOI: http://doi.org/10.3346/jkms.2005.20.1.56

Abstract

Barrett's esophagus is a premalignant condition of esophageal adenocarcinoma. Inducible nitric oxide synthase (iNOS) is induced by cytokines and can generate locally high concentrations of nitric oxide (NO), whose metabolites can mediate genotoxicity and influence multistage carcinogenesis by causing DNA damage. Therefore, we evaluated the immunolocalization and expression of iNOS in surgically induced rat Barrett's esophagus. Esophagoduodenal anastomosis was performed in rats for inducing reflux of duodenal contents. Rats were killed at postoperative 10, 20, 30 and 40 weeks. We examined histologic changes and iNOS expression in esophagus by immunohistochemistry and reverse transcription-poly-merase chain reaction. Eighty six percent of experimental rats showed Barrett's esophagus above esophagoduodenal junction. iNOS immunoreactivity was clearly observed in the epithelial cells of Barrett's esophagus, predominantly at the apical surface of epithelial cells. Cytoplasmic staining was also seen only in atypical Barrett's esophagus. iNOS mRNA was detected only in the lower esophagus of experimental group. In conclusion, this study suggests that iNOS has some roles on Barrett's esophagus formation.

Keyword

Barrett Esophagus; inducible nitric oxide synthase

MeSH Terms

Anastomosis, Surgical
Animals
Barrett Esophagus/*enzymology/*surgery
Cytoplasm/metabolism
DNA Damage
Disease Models, Animal
Duodenum/*enzymology/surgery
Esophagus/metabolism
Immunohistochemistry
Male
Models, Anatomic
Neoplasms, Experimental/pathology
Nitric Oxide/metabolism
Nitric-Oxide Synthase/*biosynthesis
RNA/metabolism
RNA, Messenger/metabolism
Rats
Rats, Sprague-Dawley
Research Support, Non-U.S. Gov't
Reverse Transcriptase Polymerase Chain Reaction
Time Factors

Figure

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  Fig. 1 End to side esophagoduodenal anastomosis.

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  Fig. 2 Gross finding of esophagoduodenal anastomosis group. Experimental rats show abnormally dilated esophagus, and esophageal inner surface displays whitish nodular patches, which are prominent in lower esophagus. Superficial ulcers are present mainly in lower esophagus. E, esophagus; E-D, anastomosis of esophagoduodenostomy site; S, stomach; D, duodenum.

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  Fig. 3 Histology and immunohistochemical staining of esophagogastric junction and Barrett's esophagus. Histology (A-D) and immunohistochemical staining (E-H, iNOS) of control esophagogastric junction (A, E) and Barrett's esophagus (B-D, F-H). Esophagogastric junction of control rats did not show iNOS expression (E). Short (F) and long (G) Barrett's esophagus revealed iNOS expression in apical surface of epithelial cells. Atypical Barrett's esophagus (H) revealed immunolocalization of iNOS in the cytoplasm of epithelial cells. Magnification: A, E, F ×400; B, C, G ×200; D, H ×100.

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  Fig. 4 iNOS expression level according to Barrett's esophagus type by immunohistochemical staining. There is no significant difference (p>0.05).

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  Fig. 5 (A) iNOS mRNA in the lower esophageal tissue of experimental rats (E) and normal one (N). (B) iNOS mRNA in the lower (LE) and upper (UE) esophagus, and duodenum (D) of experimental rats.

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