Chemoprevention of carcinogenic progression to Esophageal adenocarcinoma by the manganese superoxide dismutase supplementation

Purpose: Oxidative stress is related to the carcinogenic pathway of reflux esophagitis to Barrett's metaplasia to esophageal adenocarcinoma (EAC). Recent studies have shown that a decreased manganese superoxide dismutase (MnSOD) level is associated with the increased incidences of Barrett's esophagus (BE) and EAC. The aim of this study was to investigate MnSOD supplementation as a chernopreventive agent to prevent oxidative injury and subsequent BE and EAC formation. Experimental Design: Our esophagoduodenal anastornotic (EDA) model was done on rats according to our established procedure and treated with Mn(III)tetrakis(4-benzoic acid) porphyrin (MnTBAP; 10 mg/kg, i.p. every 3 days). Histologic changes Were determined after the EDA model at 1, 3, and 6 months. Lipid peroxidation and 8-hydroxy-deoxyguanosine for DNA oxidative damage were determined by thiobarbituric acid-reactive substance assay and immunohistochemical staining. Enzymatic activities of MnSOD and Cu/ZnSOD were evaluated, and the rate of proliferation was determined by proliferating cell nuclear antigen staining. Results: Severe esophagitis was seen in 100% of the EDA rats, and morphologic transformation within the esophageal epithelium was observed with intestinal metaplasia (40% of animals) and cancer (40% of animals) identified after 3 months. Decreased oxidative damage, along with the decreased degree of esophagitis and incidence of BE (20%) and EAC (0%), was found in MnTBAP-treated EDA rats comparing with the saline-treated EDA control. Decreased proliferation (46%) and increased SOD enzymatic activities (25%) were also found in the EDA rats treated with MnTBAP. Conclusion: MnTBAP protected rat esophageal epithelium from oxidative injury induced by EDA, and it could prevent the transformation of esophageal epithelial cell to BE to EAC by preservation of antioxidants.