Effect of aspirin treatment on the prevention of esophageal adenocarcinoma in a rat experimental model

Abstract

Abstract. Aspirin has been proposed in recent years as a candidate for chemoprevention of adenocarcinoma in patients with Barrett's esophagus. The aim of the present study was to evaluate the effect of acetylsalicylic acid (ASA) in an experimental model of esophageal adenocarcinoma. An animal model of gastroenteroesophageal reflux was established using Wistar rats undergoing esophagojejunostomy with gastric preservation. Following surgery, rats were divided into three groups: i) control (vehicle); ii) ASA 50 mg/kg/day; and iii) ASA 5 mg/kg/day. Four months after surgery, the surviving animals were sacrificed and the rat esophagi were assessed for histological and biochemical [prostaglandin E 2 (PGE 2 ) and lipoxin A 4 (LXA 4 ) levels] analysis. As in the control rats, those receiving aspirin treatment showed no decrease in inflammation grade, extent of ulcerated esophageal mucosa, length of intestinal metaplasia in continuity with anastomosis, presence of intestinal metaplasia beyond anastomosis, severity of dysplasia or incidence of adenocarcinoma. In contrast, aspirin-treated rats showed decreased esophageal tissue levels of PGE 2 and increased LXA 4 , significantly in the high-dose aspirin group (P=0.008 and P=0.01, respectively). In this rat model of gastroesophageal reflux, the administration of aspirin modified esophageal tissue levels of PGE 2 and LXA 4 , but was not effective in preventing the development of esophageal adenocarcinoma.

Promises and Limitations of Current Models for Understanding Barrett’s Esophagus and Esophageal Adenocarcinoma

“…In one example, after EJ with gastric preservation and 4 months of aspirin (0, 5, or 50 mg/kg/day), tissue levels of prostaglandin E 2 levels were reduced in rats on high-dose aspirin, with no reduction in neoplasia. 76 In a different study 40 weeks after EJ, administration of ursodeoxycholic acid was associated with 10% vs 71% rate of columnar cells in the esophagus and no adenocarcinoma vs 64% in controls. 77 In another study 40 weeks after EJ, a traditional Japanese medicine, hangeshashinto (TJ-14), was associated with a reduction in prostaglandin E 2 levels, reduced rates of columnar lining (50% vs 83% in control), and less adenocarcinoma (10% vs 67% in control).…”

Low-Dose Acetylsalicylic Acid Reduces T Cell Immune Activation: Potential Implications for HIV Prevention

“…At low doses, ASA acts as an anticoagulation drug, which blocks the normal function of the cyclooxygenase (COX)-1 and -2 enzymes ( 4 ). By blocking the function of the COX enzymes, ASA prevents the synthesis of the pro-inflammatory lipids thromboxane ( 5 ) and some prostaglandins ( 6 ) while inducing the synthesis of the anti-inflammatory 15-epi-lipoxin ( 7 ). Furthermore, ASA inhibits the activation of NF-κB thereby blocking transcription of pro-inflammatory mediators ( 8 ) resulting in decreased infiltration of immune cells into tissues ( 9 ).…”

DataSheet_1.pdf

“…At low doses, ASA acts as an anticoagulation drug, which blocks the normal function of the cyclooxygenase (COX)-1 and -2 enzymes (4). By blocking the function of the COX enzymes, ASA prevents the synthesis of the pro-inflammatory lipids thromboxane (5) and some prostaglandins (6) while inducing the synthesis of the anti-inflammatory 15-epi-lipoxin (7). Furthermore, ASA inhibits the activation of NF-kB thereby blocking transcription of pro-inflammatory mediators (8) resulting in decreased infiltration of immune cells into tissues (9).…”