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

Figure 1 Pathological findings in the esophagus of rats with esophagojejunostomy. (A) Development of intestinal metaplasia in the area of anastomosis contiguous to the jejunal epithelium. Characteristic jejunal epithelial villi (white arrow) contrast with blunt villi of metaplastic areas (black arrow). The gray arrow shows the site of anastomosis (H&E staining, ×12.5); (B) A higher magnification of (A) shows the metaplastic epithelium in detail, with incomplete development of villi and crypts lined by absorptive cells with brush borders and goblet cells (H&E, ×100); (C) Intestinal metaplasia developed distant from the anastomosis, consisting of isolated goblet cells immersed within squamous epithelium (H&E, ×100); (D) Formation of mucus glands in squamous epithelium; (E) Development of mucinous adenocarcinoma from metaplasia in continuity, infiltrating the esophageal wall in depth. The site of anastomosis is shown by the gray arrow (H&E, ×12.5).

Figure 2 Superoxide anion levels in distal esophagus at different time points (A) and in different types of lesion (B) after esophagojejunostomy. ^aP<0.05 vs control group (sham-operated rats) (n = 6-10).

Figure 3 Superoxide dismutase levels in distal esophagus at different time points (A) and in different types of lesion (B) after surgery. ^aP<0.05 vs control group (sham-operated rats) (n = 6-10).

Figure 4 Representative nitrotyrosine immunohistochemical staining in the distal esophagus of rats without reflux (sham operation), showing weak and superficial staining (A) and stronger staining (B) in the cytoplasm of squamous epithelial cells of rats after 8 weeks of reflux (esophagojejunostomy).

Figure 5 Cu, Zn-SOD and MnSOD expression in total protein extracts from sham-operated rats and rats with esophagojejunostomy. (A) A band of 16 ku corresponding to Cu, Zn-SOD observed in both normal rats and rats with enteroesophageal reflux; (B) Esophagojejunostomy-induced progressive increase of MnSOD expression; (C) Absent or weak nitrated MnSOD in control esophagus and its increase after esophagojejunostomy. Lanes 1-3: sham-operated rats; lanes 4-6: esophagojejunostomy 2 mo of evolution; lanes 7-8: esophagojejunostomy 4 mo of evolution; lane 9: molecular weight marker.

Figure 6 Incidence of intestinal metaplasia distant from the anastomosis site (A) and esophageal adenocarcinoma (B). The risk of both intestinal metaplasia and adenocarcinoma was significantly lower in the SOD-treated group than in the control group (P = 0.046 and P = 0.021, respectively) (n = 6-10).