Superoxide dismutase prevents development of adenocarcinoma in a rat model of Barrett’s esophagus

Piazuelo, Elena; Cebrián, Carmelo; Escartín, Alfredo; Jiménez, Pilar; Soteras, Fernando; Ortego, Javier; Lanas, Ángel

doi:10.3748/wjg.v11.i47.7436

Cited by 32 publications

(19 citation statements)

References 28 publications

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“…A progressive increase of MnSOD is found after EDA 3 and 6 months, which is corresponding to our previous observation (13,26). The increased MnSOD levels in the esophageal epithelium of EDA rat may reflect an adaptive process and the reasons could be as follows: (a) MnSOD is an inducible antioxidant and it can be induced to a high level by several stimuli, including oxidative stress and inflammatory (32), or (b) a compensatory mechanism against the decreased MnSOD enzymatic activity (14). In this regard, although there is a relative higher MnSOD level in the EDA esophageal epithelium, it is possible that the scavenging effect of SOD might be insufficient to decrease mucosal injury induced by continuous reflux extending over a much longer period.…”

Section: Discussionmentioning

confidence: 64%

Chemoprevention of Carcinogenic Progression to Esophageal Adenocarcinoma by the Manganese Superoxide Dismutase Supplementation

Martin¹,

Liu²,

Wo³

et al. 2007

Clinical Cancer Research

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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.Esophageal adenocarcinoma (EAC) has received considerable attention because of the dramatically increased incidence in the past 2 decades and the poor prognoses with a 5-year survival rate of 10% to 20% (1 -5). Currently, it is widely accepted that a cause-effect relationship exists between gastroesophageal reflux disease and EAC. Oxidative stress has been proposed to be closely related to the carcinogenic progression of reflux esophagitis, Barrett's metaplasia, and EAC. It has been shown that reactive oxygen species increase with the grade of reflux esophagitis and are highest in Barrett's esophagus (BE) in clinical patients (6). Several studies have also shown that reactive oxygen species cause DNA injury, such as strand breakage, alterations in guanine and thymine bases, and DNA cross-linkage (7,8). Therefore, oxidative DNA damage may contribute to the accumulation of genetic damage, and the accumulation of genetic and epigenetic aberrations produces one or more clones with metaplastic and/or malignant potential (9).In our previous studies using an external esophageal perfusion rat model (10 -13), we have shown significant increased levels of lipid peroxidation and 8-hydr...

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Section: Discussionmentioning

confidence: 64%

Chemoprevention of Carcinogenic Progression to Esophageal Adenocarcinoma by the Manganese Superoxide Dismutase Supplementation

Martin¹,

Liu²,

Wo³

et al. 2007

Clinical Cancer Research

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“…ROS scavengers can reduce esophageal mucosal damage. For example, SOD prevents the development to BE and EA in rats (231). Supplementation of ␣-tocopherol decreases EA progression in rats (50).…”

Section: Reflux Esophagitis Barrett's Esophagus and Esophageal Adenmentioning

confidence: 99%

Oxidative Stress: An Essential Factor in the Pathogenesis of Gastrointestinal Mucosal Diseases

Bhattacharyya

Chattopadhyay

Mitra

et al. 2014

Physiological Reviews

1,784

1,258

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Reactive oxygen species (ROS) are generated as by-products of normal cellular metabolic activities. Superoxide dismutase, glutathione peroxidase, and catalase are the enzymes involved in protecting cells from the damaging effects of ROS. ROS are produced in response to ultraviolet radiation, cigarette smoking, alcohol, nonsteroidal anti-inflammatory drugs, ischemia-reperfusion injury, chronic infections, and inflammatory disorders. Disruption of normal cellular homeostasis by redox signaling may result in cardiovascular, neurodegenerative diseases and cancer. ROS are produced within the gastrointestinal (GI) tract, but their roles in pathophysiology and disease pathogenesis have not been well studied. Despite the protective barrier provided by the mucosa, ingested materials and microbial pathogens can induce oxidative injury and GI inflammatory responses involving the epithelium and immune/inflammatory cells. The pathogenesis of various GI diseases including peptic ulcers, gastrointestinal cancers, and inflammatory bowel disease is in part due to oxidative stress. Unraveling the signaling events initiated at the cellular level by oxidative free radicals as well as the physiological responses to such stress is important to better understand disease pathogenesis and to develop new therapies to manage a variety of conditions for which current therapies are not always sufficient.

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“…A separate study demonstrated decreased SOD expression with more advanced neoplasia in BE [Hermann et al 2005]. Rats fed diets supplemented with manganese-SOD developed significantly fewer EACs as compared to control rats [Martin et al 2007;Piazuelo et al 2005].…”

Section: Antioxidantsmentioning

confidence: 89%

Review: Chemoprevention of esophageal adenocarcinoma

Abrams

2008

Therap Adv Gastroenterol

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The incidence of esophageal adenocarcinoma (EAC) is rising rapidly in Western countries, and effective chemoprevention for this malignancy is lacking. Endoscopic surveillance of patients with Barrett's esophagus is currently employed to diagnose EAC at earlier stages, but this strategy has several limitations. Non-steroidal anti-inflammatory drugs and proton pump inhibitors are the most promising agents for prevention of EAC, and a randomized controlled trial of aspirin and esomeprazole is ongoing. Other agents under investigation include green tea, berries, and antioxidants. Cost-effectiveness analyses have shown that chemopreventive agents need to be highly effective at preventing EAC in order to have benefit beyond endoscopic surveillance.

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Superoxide dismutase prevents development of adenocarcinoma in a rat model of Barrett’s esophagus

Abstract: 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.

Cited by 32 publications

References 28 publications

Chemoprevention of Carcinogenic Progression to Esophageal Adenocarcinoma by the Manganese Superoxide Dismutase Supplementation

Chemoprevention of Carcinogenic Progression to Esophageal Adenocarcinoma by the Manganese Superoxide Dismutase Supplementation

Oxidative Stress: An Essential Factor in the Pathogenesis of Gastrointestinal Mucosal Diseases

Review: Chemoprevention of esophageal adenocarcinoma

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