Rat Esophagus Research Articles

Indicators of humoral immunity under chemical burns of esophagus in rats

It is well known that the immune system has been actively involved in the regeneration and healing processes of post burn wounds. However, unanswered questions remain concerning the role of humoral immunity in the healing mechanisms and development of burn wound complications. We have developed an experimental model of chemical esophageal burn (CEB) which corresponds to esophageal burn in 1-8 years old children. We studied the features of humoral immunity upon CEB in rats. A decrease in IgG levels and an increase in levels of medium- and low- molecular circulating immune complexes (CIC) on the first day of esophageal burns were observed. On the 21st day of burn, we observed an increase in the IgG concentration and a tendency to accumulation of medium- and low-molecular CIC. The studied indicators can be used to differentiate CEB development and create a timeline of burn wounds.

Experimental study of the relationship between the angiopoietin-1/tyrosine kinase receptors-2 system and the neoangiogenesis in lower esophagus of rats with portal hypertension

Objective To establish a rat model of portal hypertension and explore the relationship between the angiopoietin-1(Ang-1)/tyrosine kinase receptors 2(Tie-2) system and the neoangiogenesis in lower esophagus of rats with portal hypertension. Methods Fifty SD rats were randomly divided into two groups:experimental group(thirty rats, partial portal vein and left suprarenal vein were ligatured to make portal hypertension model) and control group(twenty rats, the portal vein and left suprarenal vein were separated but not ligatured). The lower esophageal tissue was obtained two weeks after the operation.The immunohistochemical streptavidin-perosidase(SP) technique was used to detect the expression of Ang-1, Tie-2 and CD34.The microvessel density (MVD) was determined by CD34 staining.The relationship between Ang-1, Tie-2 and the neoangiogenesis in lower esophagus was analyzed after that. Results The models of portal hypertension were set up successfully in 37 rats(17 in experimental group and 20 in control group).Compared with those of control group, the differences in the expression of Ang-1, Tie-2 and MVD were statistically significant(P 0. 05), but the expression of Tie-2 was positively correlated with MVD(r= 0. 71, P< 0. 05). Conclusion The expression of Ang-1, Tie-2 and MVD is obviously higher in lower esophagus of rats in experimental group than that in the control group.The Ang-1/Tie-2 system is possibly related to the neoangiogenesis in lower esophagus of rats with portal hypertension. Key words: Portal hypertension; Angiopoietin-1; Tyrosine kinase receptors 2; Microvessel density

In oesophageal squamous cells, nitric oxide causes S-nitrosylation of Akt and blocks SOX2 (sex determining region Y-box 2) expression

ObjectiveBarrett's metaplasia might develop if GORD causes oesophageal squamous cells to convert into columnar cells. Acid and bile exposures upregulate columnar differentiation genes like CDX2 in oesophageal squamous cells, but...

Tu1155 Stress Softening Behavior in the Mucosa-Submucosa and Muscle Layers in Normal and Diabetic Rat Esophagus

Tu1155 Stress Softening Behavior in the Mucosa-Submucosa and Muscle Layers in Normal and Diabetic Rat Esophagus

Distribution of Interstitial Cells of Cajal in the Esophagus of Fetal Rats with Esophageal Atresia

Distribution of Interstitial Cells of Cajal in the Esophagus of Fetal Rats with Esophageal Atresia

Differential responses to steroid hormones in fibroblasts from the vocal fold, trachea, and esophagus.

There is accumulating evidence that fibroblasts are target cells for steroids such as sex hormones and corticoids. The characteristics of fibroblasts vary among tissues and organs. Our aim in this study is to examine differences in responses to steroid hormones among fibroblasts from different cervicothoracic regions. We compared the actions of steroid hormones on cultured fibroblasts from the vocal folds, which are considered to be the primary target of steroid hormones, and the trachea and esophagus in adult male rats. Expression of steroid hormone receptors (androgen receptor, estrogen receptor α, and glucocorticoid receptor) was identified by immunofluorescence histochemistry. Androgen receptor was much more frequently expressed in fibroblasts from the vocal fold than in those from the trachea and esophagus. Cell proliferation analysis showed that administration of testosterone, estradiol, or corticosterone suppressed growth of all 3 types of fibroblasts. However, mRNA expression for extracellular matrix-associated genes, including procollagen I and III and elastin, and hyaluronic acid synthase I was elevated only by addition of testosterone to fibroblasts from the vocal fold. These results indicate that each steroid hormone exerts region-specific effects on cervicothoracic fibroblasts with different properties through binding to specific receptors.

Pirfenidone prevents rat esophageal stricture formation

BackgroundAccidental ingestion of caustic substances induces esophageal injuries and stenosis formation. The main aim for acute phase treatment is to prevent esophageal stenosis. Pirfenidone (PFD) is a pyridone with antifibrotic and anti-inflammatory effects. Esophagus stenosis takes place after a strong inflammation process where proinflammatory and profibrogenic cytokines play an important role. The present study investigates the efficacy of PFD on the prevention of stricture development after esophageal caustic injuries in a rat model. Material and methodsCaustic esophageal burn was produced by application of 32% of NaOH to the distal esophagus of healthy rats. PFD in the form of 8% gel was administered at a dose of 200 mg/kg/d. Animals were divided in three experimental groups as follows: healthy rats, animals injured with NaOH without PFD treatment, and rats injured with NaOH and treated with PFD. Efficacy of the treatment was assessed by measuring image esophagoscopy and esophagography with contrast barium at the 21st d. Histology staining with Sirius-red was performed to evaluate collagen deposition and stenosis area. Gene expression of transforming growth factor β1, collagen-1, plasminogen activator inhibitor-1, connective tissue growth factor, and matrix metalloproteinase 2 were measured by quantitative reverse transcription polymerase chain reaction. ResultsThere was significant difference in means of stenosis by esophagoscopy and esophagogram. Collagen deposition in the damaged area increased significantly when rats were burned with NaOH, and decreased notably in PFD treated group. Profibrogenic key molecules transforming growth factor β1, collagen 1, plasminogen activator inhibitor-1 and connective tissue growth factor expression were significantly lower respect to control group without PFD treatment where matrix metalloproteinase 2 expression was no different in all groups. ConclusionsThis study suggests that PFD reduces stenosis on caustic esophageal burn by decreasing profibrogenic genes expression and ameliorates fibrosis significantly in the chronic phase.

Selective inhibition of nitric oxide synthase causes increased muscle thickness in rat esophagus

AimAchalasia is a primary motor dysfunction of esophagus which can be created experimentally by nitric oxide synthase (NOS) inhibition. Although several theories have been suggested, mechanism of increased esophageal muscle thickness in achalasia is still unclear. An experimental study was performed to evaluate the esophageal muscle thickness after selective inhibition of NOS in rats. Materials and methodsWistar albino rats (n=18) weighing 150–200g of both sexes were included in the study. After anesthetization with ketamine hydrochloride, esophageal body and distal esophagus were sampled in control group (CG, n=6). In sham group (SG, n=6), intraperitoneal saline (1ml) injection was performed for 21days. l-NAME (l-nitroarginin metyl ester, selective inhibitor of NOS) group (LNAMEG, n=6) received 100mg/kg/d l-NAME intraperitoneally for 21days. The esophageal body and distal esophagus were removed for histopathological analysis in each group. All samples were evaluated for total and circular muscle thickness with hemotoxylene–eosine (HE) staining. ResultsNone of the samples showed pathologic finding in esophageal mucosa. There was no difference between CG and SG for total and circular muscle thickness in esophageal body and distal esophagus. LNAMEG had higher median levels of both total and circular muscle thickness than CG and SG in esophageal body (P<0.05). However, in distal esophageal segments, only total muscle thickness was statistically higher in LNAMEG than CG and SG (P<0.05). ConclusionSelective inhibition of NOS causes increased total smooth muscle thickness in esophageal body and distal esophagus. However, this effect could not detected in circular muscle in the distal esophagus. We suggest that NOS inhbition not only increases esophageal peristalsis but also causes muscle hypertrophy in esophagus.

Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophageal and intestinal microvascular endothelial cells

Polyphenolic compounds (anthocyanins, flavonoid glycosides) in berries prevent the initiation, promotion, and progression of carcinogenesis in rat's digestive tract and esophagus, in part, via anti-inflammatory pathways. Angiogenesis has been implicated in the pathogenesis of chronic inflammation and tumorigenesis. In this study, we investigated the anti-inflammatory and anti-angiogenic effects of black raspberry extract (BRE) on two organ specific primary human intestinal microvascular endothelial cells, (HIMEC) and human esophageal microvascular endothelial cells (HEMEC), isolated from surgically resected human intestinal and donor discarded esophagus, respectively.HEMEC and HIMEC were stimulated with TNF-α/IL-1β with or without BRE. The anti-inflammatory effects of BRE were assessed based upon COX-2, ICAM-1 and VCAM-1 gene and protein expression, PGE2 production, NFκB p65 subunit nuclear translocation as well as endothelial cell–leukocyte adhesion. The anti-angiogenic effects of BRE were assessed on cell migration, proliferation and tube formation following VEGF stimulation as well as on activation of Akt, MAPK and JNK signaling pathways.BRE inhibited TNF-α/IL-1β-induced NFκB p65 nuclear translocation, PGE2 production, up-regulation of COX-2, ICAM-1 and VCAM-1 gene and protein expression and leukocyte binding in HEMEC but not in HIMEC. BRE attenuated VEGF-induced cell migration, proliferation and tube formation in both HEMEC and HIMEC. The anti-angiogenic effect of BRE is mediated by inhibition of Akt, MAPK and JNK phosphorylations.BRE exerted differential anti-inflammatory effects between HEMEC and HIMEC following TNF-α/IL-1β activation whereas demonstrated similar anti-angiogenic effects following VEGF stimulation in both cell lines. These findings may provide more insight into the anti-tumorigenic capacities of BRE in human disease and cancer.

Abstract 1247: Assessment of the roles of prostaglandin E2 receptors in a rodent model of chemically induced esophageal carcinogenesis

Abstract Esophageal carcinogenesis is a multistage process characterized by morphological changes from normal esophagus to basal cell hyperplasia, dysplasia, carcinoma in situ and squamous cell carcinoma (SCC). Our laboratory has used a rodent model of N-nitrosomethylbenzylamine (NMBA)-induced esophageal SCC to investigate molecular carcinogenesis and identify putative chemopreventive agents. In our previous studies, we found that the expression of cyclooxygenase-2 and the production of prostaglandin E2 (PGE2) in rat esophageal epithelium were elevated in papillomatous lesions relative to precancerous and normal tissues. PGE2 exerts its cellular effect by binding to its cognate receptors. There are four subtypes of PGE2 receptors, EP1, EP2, EP3 and EP4, which are involved in carcinogenesis depending on the cell or tissue types. The overall objective of the current study was to assess the roles of PGE2 receptors in NMBA-induced rat esophageal tumorigenesis. F344 rats were injected subcutaneously with NMBA (0.30 mg/kg b.w.) three times per week for five weeks. One week after NMBA treatment, animals were randomized into five experimental groups and fed 300 ppm celcecoxib plus 50 ppm S,S'-1,4-phenylenebis(1,2-ethanediyl)bisisothiourea (PBIT) starting from week 6, 9, 12 , or 15, respectively, or 5% freeze-dried black raspberries (BRB) starting from week 6. Esophagi were collected at 29 weeks. Results of real-time PCR, western blot analysis and immunohistochemistry demonstrated a correlation between the upregulation of EP1, EP2, EP3 and EP4 and neoplastic progression in the rat esophagus. The expression of the PGE2 receptors in preneoplastic tissues and papillomas was significantly elevated when compared to normal tissues. Moreover, we observed that celecoxib + PBIT and 5% BRB significantly reduced EP2 expression. Our data suggest, therefore, that the production of PGE2 receptors by the esophageal epithelium is associated with the development of NMBA-induced esophageal tumorigenesis in rats, and EP2 antagonist may have chemopreventive potential in esophageal cancer. Research efforts are needed to elucidate the function of PGE2 receptors and related oncogenic pathways in esophageal SCC. (Supported by NIH/NCI R01 CA131073-01A1). Citation Format: Ni Shi, Tong Chen. Assessment of the roles of prostaglandin E2 receptors in a rodent model of chemically induced esophageal carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1247. doi:10.1158/1538-7445.AM2014-1247

Abstract 1253: Dual PI3K/mTOR inhibitor NVP-BEZ235 in combination with AKT inhibitor MK2206 in esophageal carcinoma cells

Abstract The long-term goal of our research is to investigate the molecular carcinogenesis of esophageal squamous cell carcinoma and to develop strategies for esophageal cancer prevention. Previous studies in our laboratory demonstrated an association between activation of PI3K/AKT/mTOR pathways and the development of N-nitrosomethylbenzylamine (NMBA)-induced tumors in the rat esophagus. The objective of current study is to evaluate the effects of NVP-BEZ235, a dual PI3K/mTOR inhibitor, and MK2206, an AKT inhibitor, alone or in combination in esophageal cancer cell lines, KYSE-70, -150, -270 and -410. The cancer cell lines were treated with different doses of NVP-BEZ235 (1, 10, 50, 100, 1000 nMol/L) and MK2206 (0.5, 1, 3, 10, 20 uMol/L), or NVP-BEZ235 100 nMol/L plus MK2206 3 uMol/L. Western blot was performed to assess the activation of PI3K/AKT/mTOR pathways. Cell proliferation, apoptosis and cell cycle were analyzed by WST1 and flow cytometry. We found that the combination of NVP-BEZ235 and MK2206 significantly reduced the phosphorylation of p-AKTT308, p-AKTS473, p-mTORS2448, p-S6S235/236 and p-4EBP1T37/46, when compared to NVP-BEZ235 (1000 nMol/L) and MK2206 (20 uMol/L) alone (p&amp;lt;0.05). The cell proliferation rate was reduced by NVP-BEZ235 1000 nMol/L, MK2206 20 uMol/L, or NVP-BEZ235 plus MK2206 to 20% (p&amp;lt;0.01), 24% (p&amp;lt;0.01) and 17% (p&amp;lt;0.01), respectively. The NVP-BEZ235 1000 nMol/L and MK2206 10 uMol/L induced apoptosis in esophageal cancer cells to 30% and 20% (p&amp;lt;0.01), respectively. NVP-BEZ235 plus MK2206 induced apoptosis in esophageal cancer cells to 45% (p&amp;lt;0.01). The combination treatment increased the proportion of cells at G0/G1 phase compared to cells treated with NVP-BEZ235 or MK2206 alone. Our results indicate that co-targeting the PI3K/mTOR and AKT signaling pathways produces synergistic activity against esophageal carcinoma cell growth. This in-vitro study provides evidence to test the efficacy of NVP-BEZ235 in combination with MK2206 in inhibition of esophageal tumor development in vivo. (Supported by NIH/NCI R01 CA131073-01A1). Citation Format: Hao Yu, Ni Shi, Zui Pan, Tong Chen. Dual PI3K/mTOR inhibitor NVP-BEZ235 in combination with AKT inhibitor MK2206 in esophageal carcinoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1253. doi:10.1158/1538-7445.AM2014-1253

Overexpression of human β-defensin 2 promotes growth and invasion during esophageal carcinogenesis.

Human β-defensin 2 (HBD-2) is an antimicrobial peptide produced by mucosal surfaces in response to microbial exposure or inflammatory cytokines. Although HBD-2 is expressed in the esophagus in response to stress and infectious agents, little is known regarding its expression and functional role in esophageal carcinogenesis. In the current investigation, normal esophagus and N-nitrosomethylbenzylamine (NMBA)-induced precancerous and papillomatous lesions of the rat esophagus were characterized for HBD-2 encoding gene Defb4 and protein. HBD-2 was found to be overexpressed in esophagi of rats treated with NMBA compared to animals in control group. Results of Real-time PCR, Western blot and immunohistochemistry demonstrated a positive correlation between the overexpression of HBD-2 and the progression of rat squamous cell carcinogenesis (SCC) in the esophagus. We also observed that HBD-2 is overexpressed in tumor tissues removed from patients with esophageal SCC. Moreover, Defb4 silencing in vitro suppresses the tumor cell proliferation, mobility and invasion in esophageal SCC cell line KYSE-150. The results from this study provide experimental evidence that HBD-2 may play an oncogenic role in the initiation and progression of esophageal SCC and thus serves as a target for chemopreventive and therapeutic interventions.

The histological study of the effect of nanosorbent “Ingo-2” on the esophagus and stomach of white rats

The histological study of the effect of nanosorbent “Ingo-2” on the esophagus and stomach of white rats

Comprehensive spectral endoscopy of topically applied SERS nanoparticles in the rat esophagus.

The early detection and biological investigation of esophageal cancer would benefit from the development of advanced imaging techniques to screen for the molecular changes that precede and accompany the onset of cancer. Surface-enhanced Raman scattering (SERS) nanoparticles (NPs) have the potential to improve cancer detection and the investigation of cancer progression through the sensitive and multiplexed phenotyping of cell-surface biomarkers. Here, a miniature endoscope featuring rotational scanning and axial pull back has been developed for 2D spectral imaging of SERS NPs topically applied on the lumenal surface of the rat esophagus. Raman signals from low-pM concentrations of SERS NP mixtures are demultiplexed in real time to accurately calculate the concentration and ratio of the NPs. Ex vivo and in vivo experiments demonstrate the feasibility of topical application and imaging of multiplexed SERS NPs along the entire length of the rat esophagus.

Increased immunoreactivity of cathepsins in the rat esophagus under chronic acid reflux esophagitis.

We have designed a stable rat chronic acid reflux esophagitis (RE) model. In gastrointestinal lesions, several lysosomal cathepsins are known to participate in epithelial permeability in cell-cell connections, such as tight junctions in ulcerative colitis. However, very few studies have focused on the distribution of cathepsins in the esophageal multilayer squamous epithelium. Therefore to clarify the role of cathepsins in RE, we investigated their immunohistological localization in the esophageal epithelium under normal conditions and after RE. Of the cathepsins examined (cathepsins B, C, D, F, H, L, S, and X), granular immunoreactivity for cathepsins B, C, D and L was observed in the control esophageal epithelia; although, their distribution differed depending on the enzyme examined. In the RE model, immunoreactivity of these cathepsins was increased in esophageal epithelial cells and activated macrophages. The immunoreactivity for cathepsins F, H, S and X was barely detectable in the control esophageal epithelium. However, in the RE model, we noticed a slight increase in the expression of cathepsins H and X in the epithelial cells. Furthermore, activated macrophages of the RE model possessed intense immunoreactivity for these cathepsins, which may have been related to esophageal inflammatory mechanisms.

Effect of modified Zhuye Shigao Decoction and its components on preventing radiation esophagitis of rats.

To investigate the effect of Modified Zhuye Shigao Decoction (MZSD) and its components on preventing radiation esophagitis of rats. One hundred Wistar rats were randomly divided into 5 groups, including the control group, radiation model group, MZSD group, Zhuye Shigao Decoction (ZSD) group, and added ingredients group, 20 rats in each group. The model of radiation esophagitis of rat was established by once local radiation of 40 Gy (330 Mu/min) with a high energy linear accelerator. The administration of Chinese medicine was continued for 14 days from 7 days before radiation application in the three treatment groups. On the 7th and 14th day, the serum was isolated and the levels of inflammatory cytokines tumor necrosis factor (TNF-α), interleukin 1β (IL-1β) and IL-8 were tested. The pathological slices of esophagus were obtained, and the pathological changes were observed. During the whole process, weight and food intake were recorded each day. On the 7th day after radiation, the esophagus of rats in the MZSD group was almost intact, and the pathological injury score was significantly lower than that of the radiation model group, ZSD group and added ingredients group (P<0.01). Compared with the control group, the body weight and food intake of rats in the radiation model group were significantly decreased, and the levels of TNF-α, IL-1β and IL-8 were significantly increased (P<0.05 or P<0.01), while the MZSD group showed a significant increase in body weight and food intake, and a significant decrease in the levels of TNF-α, IL-1β and IL-8 compared with the radiation model group, ZSD group and added ingredients group (P <0.05 or P<0.01). MZSD prevents the development of radiation esophagitis probably by inhibiting the generation and release of the inflammatory cytokines TNF-α, IL-1β and IL-8.

P49 Inhibitory actions of hydrogen sulfide on contractions of the esophageal striated muscle

Inhibitory effects of hydrogen sulfide (H2S) on the smooth muscle motility of the ileum and the colon have been reported. However, it is unclear whether H2S can affect the esophageal motility. Therefore, the aim of the present study was to clarify the effects of H2S on the motility of the esophageal striated muscle in the rat. An isolated segment of the rat esophagus was placed in an organ bath and the mechanical responses were recorded using a force transducer. Electrical stimulation of the vagus nerve evoked the contractile response in the esophageal segment. The vagally mediated contraction was inhibited by application of a H2S donor, NaHS. NaHS did not affect the contraction induced by electrical field stimulation, which directly can excite the striated muscle not via vagus nerves. This shows that H2S can influence not directly the striated muscle but neurons. RT-PCR revealed the expression of CBS and CSE mRNA in the esophageal tissue. These findings suggest that H2S might be produced in the esophageal tissue and might regulate the motility of the esophageal striated muscle.

Contractions reverse stress softening in rat esophagus.

Strain/stress induced tissue softening is usually referred to irreversible softening. The aim of this study was to investigate whether stress softening in rat esophagus is reversible after potassium chloride (KCl) induced contraction. Three series of inflation-deflation loadings were carried out on esophageal specimens obtained from 20 Wistar rats. All specimens were subjected to the first two series in Ca(2+)-free Krebs solution(Krebs(-)) and then incubated in Ca(2+)-containing Krebs solution (Krebs(+)) for 1 h. Ten specimens were distended to pressure 1.0 kPa and activated with KCl for 3 min. The other ten specimens, however, were distended to 1.0 kPa without KCl activation. Subsequently, after incubation in Krebs(-) for 1 h, all 20 specimens were subjected to the third series testing. The stored energy in the esophageal tissues (hysteresis loop area) and the esophageal wall stiffness were compared between two groups within the three series loadings. Results indicated that incubation in Krebs(+) cannot recover the stress softening induced energy and stiffness loss, but in contrast, these loss were recovered markedly (p < 0.05) after KCl activation. In conclusion, stress softening in rat esophagus is reversible after the activation of KCl-induced contractions. This mechanism could be related to regeneration of tissue properties in rat esophagus.

Pharmacological profile of DA-6886, a novel 5-HT4 receptor agonist to accelerate colonic motor activity in mice

DA-6886, the gastrointestinal prokinetic benzamide derivative is a novel 5-HT4 receptor agonist being developed for the treatment of constipation-predominant irritable bowel syndrome (IBS-C). The purpose of this study was to characterize in vitro and in vivo pharmacological profile of DA-6886. We used various receptor binding assay, cAMP accumulation assay, organ bath experiment and colonic transit assay in normal and chemically constipated mice. DA-6886 exhibited high affinity and selectivity to human 5-HT4 receptor splice variants, with mean pKi of 7.1, 7.5, 7.9 for the human 5-HT4a, 5-HT4b and 5-HT4d, respectively. By contrast, DA-6886 did not show significant affinity for several receptors including dopamine D2 receptor, other 5-HT receptors except for 5-HT2B receptor (pKi value of 6.2). The affinity for 5-HT4 receptor was translated into functional agonist activity in Cos-7 cells expressing 5-HT4 receptor splice variants. Furthermore, DA-6886 induced relaxation of the rat oesophagus preparation (pEC50 value of 7.4) in a 5-HT4 receptor antagonist-sensitive manner. The evaluation of DA-6886 in CHO cells expressing hERG channels revealed that it inhibited hERG channel current with an pIC50 value of 4.3, indicating that the compound was 1000-fold more selective for the 5-HT4 receptor over hERG channels. In the normal ICR mice, oral administration of DA-6886 (0.4 and 2mg/kg) resulted in marked stimulation of colonic transit. Furthermore, in the loperamide-induced constipation mouse model, 2mg/kg of DA-6886 significantly improved the delay of colonic transit, similar to 10mg/kg of tegaserod. Taken together, DA-6886 is a highly potent and selective 5-HT4 receptor agonist to accelerate colonic transit in mice, which might be therapeutic agent having a favorable safety profile in the treatment of gastrointestinal motor disorders such as IBS-C and chronic constipation.

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

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 50mg/kg/day; and iii) ASA 5mg/kg/day. Four months after surgery, the surviving animals were sacrificed and the rat esophagi were assessed for histological and biochemical [prostaglandin E2 (PGE2) and lipoxin A4 (LXA4 ) 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 PGE2 and increased LXA4, 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 PGE2 and LXA4, but was not effective in preventing the development of esophageal adenocarcinoma.