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


CONCLUSIONS
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.
Piazuelo
Elena
E
Instituto Aragonés de Ciencias de la Salud, Unidad Mixta de Investigación, Zaragoza, Spain. epiazor@unizar.es
Cebrián
Carmelo
C
Escartín
Alfredo
A
Jiménez
Pilar
P
Soteras
Fernando
F
Ortego
Javier
J
Lanas
Angel
A
D000230:Adenocarcinoma / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D001471:Barrett Esophagus / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000209:etiology / Q000517:prevention & control*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000494:pharmacology*
D016166:Free Radical Scavengers; D013482:Superoxide Dismutase