Free radicals and antioxidant systems in reflux esophagitis and Barrett's esophagus.
OBJECTIVE
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.


CONCLUSIONS
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.
Jiménez
Pilar
P
Aragonés Institute of Health Sciences, and Gastroenterology Service, Lozano Blesa University Hospital Clinic, Avenida San Juan Bosco, C/Domingo Miral, s/n. 15-50009 Zaragoza, Spain. pilarj@unizar.es
Piazuelo
Elena
E
Sánchez
M Teresa
MT
Ortego
Javier
J
Soteras
Fernando
F
Lanas
Angel
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism*; D004941:Esophagitis / Q000209:etiology* / Q000378:metabolism*; D005260:Female; D005609:Free Radicals / Q000378:metabolism*; D005764:Gastroesophageal Reflux / Q000150:complications*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D005609:Free Radicals; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D010088:Oxidoreductases; D013482:Superoxide Dismutase; D005978:Glutathione