ascorbic-acid and Esophagitis--Peptic

There is a strong male predominance of oesophageal adenocarcinoma, which might be related to the higher prevalence of precursor lesions such as erosive reflux oesophagitis in men compared with women. This experiment investigated the gender difference in a reflux oesophagitis model of rats and explored the potential role of oestrogen in controlling oesophageal tissue damage.. An acid-reflux oesophagitis model was surgically produced in male and female rats, and ascorbic acid in the diet and sodium nitrite in the drinking water were administered to half of either group to provoke luminal exogenous nitric oxide (NO) as an exacerbating agent. Seven days after the surgery, the oesophagus was excised, and the injury area, myeloperoxidase activity and pro-inflammatory cytokine levels were measured. Furthermore, 17β-oestradiol was administered to ovariectomised female rats or male rats, which then underwent reflux oesophagitis surgery.. While there was no gender difference in oesophageal damage in the baseline model, oesophageal damage was more intensively observed in males than in females in the presence of exogenous NO administration. While oesophageal damage was increased in ovariectomised rats compared with sham ovariectomised, exacerbated oesophageal damage was attenuated by the replacement of 17β-oestradiol. In addition, exacerbated oesophageal damage in male rats was suppressed by 17β-oestradiol.. This is the first study showing the prominent gender difference in the severity of oesophageal tissue damage in a gastro-oesophageal reflux disease-related animal model, highlighting the critical involvement of oestrogen in controlling gastro-oesophageal reflux disease-related oesophageal epithelial injury.

Topics: Animals; Ascorbic Acid; Biomarkers; Chronic Disease; Cytokines; Disease Models, Animal; Esophagitis, Peptic; Esophagus; Estradiol; Estrogens; Female; Gastroesophageal Reflux; Male; Mucous Membrane; Nitric Oxide; Ovariectomy; Peroxidase; Random Allocation; Rats; Rats, Wistar; Severity of Illness Index; Sex Factors; Sodium Nitrite; Stomach

The incidence of esophageal adenocarcinoma in humans is increasing more rapidly than any other malignancy in the United States. Animal studies have demonstrated the efficacy of freeze-dried berry supplementation on carcinogen-induced esophageal squamous cell carcinoma in rats; however, no such studies have been done in esophagoduodenal anastomosis (EDA), an animal model for reflux-induced esophageal adenocarcinoma (EAC) development. Eight-week-old male Sprague-Dawley rats were randomized into 3 groups: EDA + control diet (EDA-CD; n = 10); EDA + 2.5% black raspberry diet (EDA-BRB; n = 11) and EDA + 2.5% blueberry diet (EDA-BB; n = 12). After 2 wk of feeding the respective diets, the rats underwent EDA surgery to induce gastroesophageal reflux and then continued the diet. Measurement of feed intake suggested that all EDA-operated animals had lower feed intake starting at 10 wk after surgery and this was significant close to termination at 24 wk. There were no significant differences in either reflux esophagitis (RE), intestinal metaplasia (IM) (70% in CD, 64% in BRB, and 66% in BB; P = 0.1) or EAC incidence (30% for CD, 34% for BRB, and 25% for BB; P = 0.2) with supplementation. Berry diets did not alter COX-2 levels, but BB diet significantly reduced MnSOD levels (1.23 ± 0.2) compared to control diet (2.05 ± 0.14; P < 0.05). We conclude that a dietary supplementation of freeze-dried BRB and BB at 2.5% (w/w) was not effective in the prevention of reflux-induced esophageal adenocarcinoma in this EDA animal model.

Topics: Adenocarcinoma; Anastomosis, Surgical; Animals; Anthocyanins; Ascorbic Acid; Biomarkers; Blueberry Plants; Cyclooxygenase 2; Dietary Supplements; Disease Models, Animal; Disease Progression; Esophageal Neoplasms; Esophagitis, Peptic; Esophagus; Food Handling; Freeze Drying; Fruit; Linear Models; Male; Plant Preparations; Rats; Rats, Sprague-Dawley; Selenium; Superoxide Dismutase; Weight Gain

Cytotoxic concentrations of nitric oxide are generated luminally at the gastroesophageal junction through the entero-salivary recirculation of dietary nitrate in humans. The site of luminal nitric oxide generation shifts to the lower esophagus when gastric acid is refluxed into the esophagus. The aim of this study was to investigate the influence of persistent administration of exogenous nitric oxide on esophageal damage.. 0.1% sodium nitrite and/or 1% ascorbic acid was administered in an established rat acid-refluxed esophagitis model. Co-administration of both reactants in this model is thought to induce high concentrations of nitric oxide luminally in the esophagus by an acid-catalyzed chemical reaction when refluxed gastric acid is present. The tissue damage was evaluated by a macroscopic lesion index and myeloperoxidase activity. Nitrotyrosin was assessed immunohistochemically as a footprint of peroxynitrite formation.. Co-administration of sodium nitrite and ascorbic acid induced a 4- to 5-fold increase in the esophageal damage compared with baseline reflux esophagitis, while the damage was unchanged when either of the reagents alone was given. Nitrotyrosine was strongly stained in the tissue from the co-administration. Treatment of superoxide scavengers efficiently prevented the exacerbation of esophageal damage by exogenous nitric oxide exposure, suggesting an essential role of superoxide in esophageal damage.. Exogenous luminal nitric oxide greatly exacerbated the tissue damage of reflux esophagitis. Diffusion of the luminal nitric oxide into the adjacent superoxide-enriched inflamed tissue of the esophagus could lead to the production of the highly toxic agent peroxynitrite, thus causing exacerbation of the esophageal damage.

Topics: Analysis of Variance; Animals; Ascorbic Acid; Biopsy, Needle; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Esophagitis, Peptic; Esophagogastric Junction; Immunohistochemistry; Male; Nitric Oxide; Omeprazole; Peroxidase; Probability; Random Allocation; Rats; Rats, Wistar; Sensitivity and Specificity

Reflux-induced injury and oxidative stress result in esophageal inflammation and the potential for progression to intestinal metaplasia and adenocarcinoma. Proton-pump inhibitors represent the standard medical approach, but anti-inflammatories and antioxidants offer novel therapeutic possibilities.. Six weeks after an esophagojejunostomy reflux procedure, female Wistar rats (n = 100) were randomized to receive either an antioxidant (vitamin C, 8 mg or 28 mg/day), a cyclooxygenase-2 (COX-2) inhibitor (rofecoxib, 1 mg/day), or no therapy. After sacrifice 16 weeks later, esophageal injury was scored using pathologic and image analysis scoring.. Esophagitis was present in all 63 animals completing the study and was severe in 27 (43%). No animal developed metaplasia or tumor. The extent of inflammation and esophageal ulceration were not significantly different between experimental groups.. In this model of reflux injury, antioxidants and COX-2 inhibitors failed to ameliorate the severe inflammation induced. Further experimental designs should evaluate these novel approaches in less severe experimental models.

Topics: Animals; Antioxidants; Ascorbic Acid; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Dose-Response Relationship, Drug; Esophagitis, Peptic; Esophagus; Female; Jejunum; Lactones; Random Allocation; Rats; Rats, Wistar; Sulfones

Combined treatment with sodium nitrite (NaNO2) and ascorbic acid (AsA) has already been shown to promote rat forestomach carcinogenesis, possibly due to nitric oxide generation under acidic conditions. We hypothesized that a similar effect might occur in the esophagus when the luminal pH is decreased by acid reflux. To clarify this possibility, reflux esophagitis model rats (F344 male) were coadministered 0.2% NaNO2 in the drinking water and 1% AsA in the diet. After 32 weeks of the combined treatment, a significant increase in the incidence of epithelial hyperplasias of the lower-middle and lowest parts of the esophagus were observed compared with the basal-diet group, along with exacerbation of dysplasia and extension of the lesions. Additionally, one squamous cell papilloma was found only in the combined-treatment group. Subsequently, we confirmed the enhancing effects of NaNO2 and AsA cotreatment in the rat N-bis(2-hydroxypropyl)nitrosamine-initiated esophageal tumorigenesis model. The incidence of hyperplasia was enhanced in all segments, along with the incidence and multiplicity of squamous cell papillomas in the lowest segment of the esophagus. Thus, the data demonstrate that combined treatment with NaNO2 and AsA exerts promoting effects on rat esophageal carcinogenesis under acid reflux conditions, as in the forestomach. These findings suggest that the risk of excessive intake of a combination of nitrite and antioxidants for esophageal carcinogenesis is appreciable, particularly in patients with reflux esophagitis.

Topics: Animals; Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Cocarcinogenesis; Disease Models, Animal; Esophageal Neoplasms; Esophagitis, Peptic; Food Preservatives; Male; Rats; Rats, Inbred F344; Sodium Nitrite

Reflux-induced injury and oxidative stress result in esophageal inflammation and the potential for progression to intestinal metaplasia and adenocarcinoma. Proton-pump inhibitors represent the standard medical approach, but anti-inflammatories and antioxidants offer novel therapeutic possibilities.. Six weeks after an esophagojejunostomy reflux procedure, female Wistar rats (n = 100) were randomized to receive either an antioxidant (vitamin C, 8 mg or 28 mg/day), a cyclooxygenase-2 (COX-2) inhibitor (rofecoxib, 1 mg/day), or no therapy. After sacrifice 16 weeks later, esophageal injury was scored using pathologic and image analysis scoring.. Esophagitis was present in all 63 animals completing the study and severe in 27 (43%). No animal developed metaplasia or tumor. The extent of inflammation and esophageal ulceration were not significantly different between experimental groups.. In this model of reflux injury, antioxidants and COX-2 inhibitors failed to ameliorate the severe inflammation induced. Further experimental designs should evaluate these novel approaches in less severe experimental models.

Topics: Animals; Antioxidants; Ascorbic Acid; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Esophagitis, Peptic; Esophagus; Female; Inflammation; Jejunum; Lactones; Models, Animal; Random Allocation; Rats; Rats, Wistar; Sulfones; Ulcer

It has been speculated that impaired salivary flow contributes to abnormal acid clearance of the esophagus in gastroesophageal reflux and results in reflux esophagitis (RE). To test this hypothesis, salivary functions were measured by quantitative salivary scintigraphies in patients with RE and in age- and sex-matched controls for comparison. Nineteen patients with RE and 36 healthy volunteers were enrolled in the study. After an intravenous injection of 5 mCi Tc-99m pertechnetate, sequential images of 1 min/frame were acquired for 30 min. The 1- and 15-min uptake ratios (UR) of the tracer in the four major salivary glands over the backgrounds were calculated. Saliva excretion was stimulated by 1 tablet of 200 mg ascorbic acid given orally 15 min after injection of the tracer, then the maximal excretion ratios (ER) of the four major salivary glands were calculated for the sialagogue stimulation. RE patients had lower values of 1st and 15th min UR and maximal ER than controls in the 4 major salivary glands. Poor salivary functions which represented a decrease in both UR and ER for patients with RE have been confirmed by quantitative salivary scintigraphy in this study.

Topics: Adult; Aged; Ascorbic Acid; Esophagitis, Peptic; Esophagoscopy; Female; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Prognosis; Radionuclide Imaging; Saliva; Salivary Gland Diseases; Salivary Glands