Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2005; 11(47): 7436-7443
Published online Dec 21, 2005. doi: 10.3748/wjg.v11.i47.7436
Superoxide dismutase prevents development of adenocarcinoma in a rat model of Barrett’s esophagus
Elena Piazuelo, Carmelo Cebrián, Alfredo Escartín, Pilar Jiménez, Fernando Soteras, Javier Ortego, Angel Lanas
Elena Piazuelo, Pilar Jiménez, Instituto Aragonés de Ciencias de la Salud, Unidad Mixta de Investigación, C/Domingo Miral s/n 50009 Zaragoza, Spain
Javier Ortego, Carmelo Cebrián, Service of Pathology, Hospital Clínico Universitario “Lozano Blesa”, Avenida San Juan Bosco, 15 50009 Zaragoza, Spain
Fernando Soteras, Alfredo Escartín, Unidad Mixta de Investigación, University of Zaragoza, Domingo Miral s/n 50009 Zaragoza, Spain
Angel Lanas, Service of Gastroenterology, Hospital Clínico Universitario “Lozano Blesa”, Avenida San Juan Bosco, 15 50009 Zaragoza, Spain
Author contributions: All authors contributed equally to the work.
Supported by grants from CICYT (SAF2000-0123) and Instituto de Salud Carlos III (C03/02). Elena Piazuelo is supported by Instituto de Salud Carlos III and Instituto Aragonés de Ciencias de la Salud
Correspondence to: Elena Piazuelo Ortega, Unidad Mixta de Investigación, Servicio de Biomedicina y Biomateriales, Universidad de Zaragoza, C/Domingo Miral, s/n. 50009 Zaragoza, Spain. epiazor@unizar.es
Telephone: +34-976-762538 Fax: +34-976-762539
Received: December 15, 2004
Revised: February 13, 2005
Accepted: February 18, 2005
Published online: December 21, 2005
Abstract

AIM: To test whether antioxidant treatment could prevent the progression of Barrett’s esophagus to adenocarcinoma.

METHODS: In a rat model of gastroduodenoesophageal reflux by esophagojejunal anastomosis with gastric preservation, groups of 6-10 rats were randomized to receive treatment with superoxide dismutase (SOD) or vehicle and followed up for 4 mo. Rat’s esophagus was assessed by histological analysis, superoxide anion and peroxinitrite generation, SOD levels and DNA oxidative damage.

RESULTS: All rats undergoing esophagojejunostomy developed extensive esophageal mucosal ulceration and inflammation by mo 4. The process was associated with a progressive presence of intestinal metaplasia beyond the anastomotic area (9% 1st mo and 50% 4th mo) (94% at the anastomotic level) and adenocarcinoma (11% 1st mo and 60% 4th mo). These changes were associated with superoxide anion and peroxinitrite mucosal generation, an early and significant increase of DNA oxidative damage and a significant decrease in SOD levels (P<0.05). Exogenous administration of SOD decreased mucosal superoxide levels, increased mucosal SOD levels and reduced the risk of developing intestinal metaplasia beyond the anastomotic area (odds ratio = 0.326; 95%CI: 0.108-0.981; P = 0.046), and esophageal adenocarcinoma (odds ratio = 0.243; 95%CI: 0.073-0.804; P = 0.021).

CONCLUSION: Superoxide dismutase prevents the progression of esophagitis to Barrett’s esophagus and adenocarcinoma in this rat model of gastrointestinal reflux, supporting a role of antioxidants in the chemoprevention of esophageal adenocarcinoma.

Keywords: Barrett’s esophagus; Esophageal adenocarcinoma; Free radicals; Oxidative damage; Superoxide dismutase