Investigation of the Gastroprotective Effect of Betaine-Homocysteine Homeostasis on Oxidative Stress, Inflammation and Apoptosis in Ethanol-Induced Ulcer Model

ABSTRACTBackground: There is a growing interest in the use of natural compounds for the treatment ofgastric ulcers. The multifunctional roles of betaine in various diseases make this natural substancea favorable pre-drug for ulcer treatment. This study aims to determine the competence of betainein gastroprotection against ethanol-induced damage and to explore underlying mechanismsconsidering its effects on liver and kidney activity and blood parameters.Methods: Wistar albino rats were orally treated with vehicle (distilled water) or betaine (250mg/kg) for twenty-one days and then ulcer formation was induced by ingestion of 75% ethanol.Gastric mucosal damage was evaluated by gross examination and histopathological analysis.Homocysteine levels, lipid peroxidation, total antioxidant status (TAS), total oxidant status (TAS),antioxidant enzymes and pro-inflammatory and anti-inflammatory cytokines levels were assessedby enzyme-linked immunosorbent assay (ELISA) or immunohistochemistry. Furthermore, routinebiochemical tests were performed and hematological parameters were analyzed.Results: Betaine ameliorated any gastric mucosal damage and reduced homocysteine levelssignificantly. The TOS and malondialdehyde (MDA) levels were decreased while the TAS, glutathione(GSH) levels and catalase (CAT) activity were increased upon the betaine treatment. Betaine reducedapoptosis by regulating Bax and Bcl-2 levels, however, it did not alter inflammatory mediators.Additionally, betaine improved serum potassium (K+) and blood urea nitrogen (BUN) levels, whereasit increased alanine aminotransferase (ALT) levels and impaired hematological parameters.Conclusions: Altogether, these data illustrated that betaine exhibits a gastroprotective effectagainst ulcers through the homocysteine pathway by modulating oxidative stress in the gastrictissue; however, its systemic effects should not be ignored.