Evaluation of the heme oxygenase-1 expression in esophagitis and esophageal cancer induced by different reflux experimental models and diethylnitrosamine.
OBJECTIVE
To study the expression of heme-oxygenase-1 (HO-1), an enzyme induced by oxidative stress, in specimens obtained from an experimental model in rats that evaluated the role of gastric and duodenal reflux in esophageal carcinogenesis.


METHODS
Esophageal specimens embedded in paraffin obtained from different experimental groups of rats were used for immunohistochemistry analysis of HO-1 expression. The rats had been divided into the following groups and were killed after 22 weeks: (1) cardioplasty to induce acid reflux; (2) esophagoduodenal anastomosis to induce duodenal reflux; (3) no treatment; (4) cardioplasty + diethylnitrosamine (DEN); (5) esophagoduodenal anastomosis + DEN; and (6) DEN. The study sample comprised 3 specimens from each group with the most severe histopathological lesions found on each study branch.


RESULTS
The expression of HO-1 was seen only in rat specimens submitted to esophagoduodenal anastomosis (Groups 2 and 5), and the analysis of mean fluorescence intensity revealed a significant increase of HO-1 expression (4.8 and 4.6 fold, respectively) when compared with the control group (Group 3) (p<0.05). The main target for HO-1 induction was the inflammatory cells inside the tumor or in subepithelial areas. Rats exposed to gastric reflux had no HO-1 expression.


CONCLUSIONS
Reflux esophagitis induced by reflux of duodenal contents, which provoked considerable oxidative stress, may play an important role in esophageal carcinogenesis. Acid reflux did not induce oxidative stress in this experimental model.
Kruel
Cleber Rosito Pinto
CR
Hospital de Clínicas de Porto Alegre, RS, Brazil. kruelrosito@yahoo.com.br <kruelrosito@yahoo.com.br>
Pinto
Luis Felipe Ribeiro
LF
Blanco
Tania Cristina Moita
TC
Barja-Fidalgo
Theresa Christina
TC
Melo
Levi Lourenzo
LL
Kruel
Cleber Dario Pinto
CD
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002273:Carcinogens; D002277:Carcinoma / Q000139:chemically induced*; D004052:Diethylnitrosamine; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000139:chemically induced*; D004941:Esophagitis / Q000139:chemically induced*; D004947:Esophagus / Q000201:enzymology; D005764:Gastroesophageal Reflux / Q000150:complications*; D051547:Heme Oxygenase-1 / Q000032:analysis*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D002273:Carcinogens; D004052:Diethylnitrosamine; D051547:Heme Oxygenase-1