Superoxide dismutase prevents development of adenocarcinoma in a rat model of Barrett's esophagus

查看全文 作　　者：Elena [1]Piazuelo;Carmelo [2]Cebrián;Alfredo [3]Escartín;Pilar [1]Jiménez;Fernando [4]Soteras;Javier [2]Ortego;Angel [5]Lanas

机构地区：[1]Instituto Aragonés de Ciencias de la Salud,Unidad Mixta de Investigación,C/Domingo Miral s/n 50009 Zaragoza,Spain;[2]Service of Pathology,Hospital Clínico Universitario 'Lozano Blesa',Avenida San Juan Bosco,15 50009 Zaragoza,Spain;[3]Unidad Mixta de Investigatión,University of Zaragoza,Domingo Miral s/n 50009 Zaragoza,Spain;[4]Unidad Mixta de Investigación,University of Zaragoza,Domingo Miral s/n 50009 Zaragoza,Spain;[5]Service of Gastroenterology,Hospital Clínico Universitario 'Lozano Blesa',Avenida San Juan Bosco,15 50009 Zaragoza,Spain

出　　处：《World Journal of Gastroenterology》索引2005年第11卷第47期,共8页

基　　金：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 Aragones de Ciencias de la Salud 摘　　要：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 beyondthe 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. 关键词：过氧化物岐化酶食管疾病病理机制治疗

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Superoxide dismutase prevents development of adenocarcinoma in a rat model of Barrett's esophagus

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