Esophageal Cancer
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2005; 11(18): 2697-2703
Published online May 14, 2005. doi: 10.3748/wjg.v11.i18.2697
Free radicals and antioxidant systems in reflux esophagitis and Barrett’s esophagus
Pilar Jiménez, Elena Piazuelo, M. Teresa Sánchez, Javier Ortego, Fernando Soteras, Angel Lanas
Pilar Jiménez, Elena Piazuelo, M. Teresa Sánchez, Angel Lanas, Instituto Aragonés de Ciencias de la Salud and Service of Gastroenterology, Hospital Clínico Universitario “Lozano Blesa”, Avenida San Juan Bosco, 15 50009 Zaragoza, Spain
Javier Ortego, Service of Pathology, Hospital Clínico Universitario “Lozano Blesa”, Avenida San Juan Bosco, 15 50009 Zaragoza, Spain
Fernando Soteras, University of Zaragoza, Domingo Miral, s/n. 50009 Zaragoza, Spain
Author contributions: All authors contributed equally to the work.
Supported by the grant FIS 99/0569 from the Fondo de Investigaciones Sanitarias and Instituto de Salud Carlos III (C03/02)
Correspondence to: Pilar Jiménez Molinos, Unidad Mixta de Investigación, C/Domingo Miral, s/n. 50009 Zaragoza, Spain. pilarj@unizar.es
Telephone: +34-976-762538 Fax: +34-976-762539
Received: August 10, 2004
Revised: August 11, 2004
Accepted: September 16, 2004
Published online: May 14, 2005
Abstract

AIM: Experimental studies suggest that free radicals are involved in acid and pepsin-induced damage of esophageal mucosa. The profile and balance between free radicals and antioxidant systems in human esophagitis are unknown.

METHODS: Superoxide anion and its powerful oxidant reaction with nitric oxide (peroxynitrite) generation were determined in esophageal mucosal biopsies from 101 patients with different gastro-esophageal reflux diseases and 28 controls. Activity of both superoxide dismutase (SOD) and catalase, and reduced glutathione (GSH) levels, were also assessed. Expression of Cu,ZnSOD, MnSOD and tyrosine-nitrated MnSOD were analyzed by Western blot and/or immunohistochemistry.

RESULTS: The highest levels of superoxide anion generation were found in patients with severe lesions of esophagitis. Peroxynitrite generation was intense in Barrett’s biopsies, weaker in esophagitis and absent/weak in normal mucosa. Expression of Cu,ZnSOD and MnSOD isoforms were present in normal mucosa and increased according to the severity of the lesion, reaching the highest level in Barrett’s esophagus. However, SOD mucosal activity significantly decreased in patients with esophagitis and Barrett’s esophagus, which was, at least in part, due to nitration of its tyrosine residues. Catalase activity and GSH levels were significantly increased in mucosal specimens from patients with esophagitis and/or Barrett’s esophagus.

CONCLUSION: A decrease in SOD antioxidant activity leading to increased mucosal levels of superoxide anion and peroxynitrite radicals may contribute to the development of esophageal damage and Barrett’s esophagus in patients with gastroesophageal reflux. Administration of SOD may be a therapeutic target in the treatment of patients with esophagitis and Barrett’s esophagus.

Keywords: Superoxide anion; Peroxynitrite; Antioxidant enzymes; Esophagitis; Barrett’s esophagus