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

Robert C.G. Martin, Qiaohong Liu, John M. Wo, Mukunda B. Ray, Yan Li

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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 chemopreventive agent to prevent oxidative injury and subsequent BE and EAC formation. Experimental Design: Our esophagoduodenal anastomotic (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.

Original languageEnglish (US)
Pages (from-to)5176-5182
Number of pages7
JournalClinical Cancer Research
Volume13
Issue number17
DOIs
StatePublished - Sep 1 2007

Fingerprint

Barrett Esophagus
Chemoprevention
Superoxide Dismutase
Adenocarcinoma
Esophagitis
Epithelium
Staining and Labeling
Peptic Esophagitis
Deoxyguanosine
Thiobarbituric Acid Reactive Substances
Incidence
Wounds and Injuries
Proliferating Cell Nuclear Antigen
Metaplasia
Lipid Peroxidation
DNA Damage
Oxidative Stress
Research Design
Antioxidants
Epithelial Cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Chemoprevention of carcinogenic progression to esophageal adenocarcinoma by the manganese superoxide dismutase supplementation. / Martin, Robert C.G.; Liu, Qiaohong; Wo, John M.; Ray, Mukunda B.; Li, Yan.

In: Clinical Cancer Research, Vol. 13, No. 17, 01.09.2007, p. 5176-5182.

Research output: Contribution to journalArticle

Martin, Robert C.G. ; Liu, Qiaohong ; Wo, John M. ; Ray, Mukunda B. ; Li, Yan. / Chemoprevention of carcinogenic progression to esophageal adenocarcinoma by the manganese superoxide dismutase supplementation. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 17. pp. 5176-5182.
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abstract = "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 chemopreventive agent to prevent oxidative injury and subsequent BE and EAC formation. Experimental Design: Our esophagoduodenal anastomotic (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.",
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