Pro-ulcerogenic activity of sodium arsenite in the gastric mucosa of male wistar rats
Background: The gastrointestinal tract is constantly exposed to various protective and aggressive factors from food and the environment. Recent studies have shown that environmental factors, including heavy metal exposure and diet may alter gastrointestinal mucosal integrity. Arsenic (extensively available in the form of oxides or sulfides or as a salt of iron, sodium, calcium, copper, etc) is a major contaminant of soil, air as well as various water sources used for human and industrial activities, making it a huge public health burden. The present study was designed to characterize gastrointestinal alterations induced by sodium arsenite (SA) exposure.
Methods: Sixty-four male Wistar rats were divided into four groups (n = 16) in two separate studies. Groups I and 2 received distilled water and indomethacin (40mg/kg, p.o) respectively while groups 3 and 4 animals received 5mg/kg and 10mg/kg SA respectively for two weeks prior to administration of indomethacin. In the first study, gastric acid secretion (GAS) was studied using the continuous perfusion technique. In the second study, animals were sacrificed after indomethacin administration. Ulcer was assessed based on macroscopic appearance of the stomach using an ulcer score scale. Each excised stomach was thoroughly cleaned and small sections were taken for histological analysis. Data were analysed using one-way ANOVA and differences considered significant at p<0.05.
Results: Basal GAS was 0.08 ± 0.004 mEq/L in control rats. Indomethacin increased GAS significantly (0.14 mEq/L). The effect of indomethacin was augmented in rats with prior exposure to SA in a dose-dependent manner (0.17±0.01 and 0.26±0.02 mEq/L respectively). In the second study, SA significantly increased mean ulcer score, parietal and mucous cell counts when compared with the unexposed groups. Moderate epithelial erosion with infiltration of inflammatory cells as well as decreased intraglandular mucin and mucous secreting cells were observed in the stomach tissues of sodium arsenite treated rats.
Conclusion: It is suggested that sodium arsenite potentiates gastric ulceration during indomethacin induced ulceration by increasing basal gastric acid secretion, increased parietal cell counts with extensive damage to the mucous secreting cells thereby distrupting the cyto-protecting ability of the stomach.
Keywords: Sodium arsenite, gastric ulcer, gastric acid secretion, parietal cell count