Background: There is a growing interest in the use of natural compounds for the treatment of
gastric ulcers. The multifunctional roles of betaine in various diseases make this natural substance
a favorable pre-drug for ulcer treatment. This study aims to determine the competence of betaine
in gastroprotection against ethanol-induced damage and to explore underlying mechanisms
considering 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 assessed
by enzyme-linked immunosorbent assay (ELISA) or immunohistochemistry. Furthermore, routine
biochemical tests were performed and hematological parameters were analyzed.
Results: Betaine ameliorated any gastric mucosal damage and reduced homocysteine levels
significantly. 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 reduced
apoptosis 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, whereas
it increased alanine aminotransferase (ALT) levels and impaired hematological parameters.
Conclusions: Altogether, these data illustrated that betaine exhibits a gastroprotective effect
against ulcers through the homocysteine pathway by modulating oxidative stress in the gastric
tissue; however, its systemic effects should not be ignored.