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We investigated the antioxidant and anti-ulcerogenic effects of fulvic acid (FA) on oxidative damage caused by water avoidance stress (WAS) in rat gastrointestinal mucosa. Three experimental groups were established: control (C), chronic stress (CS), and chronic stress + FA (CS + FA). After WAS, a single dose of FA was administered for 10 days to the CS + FA group. Samples of the pyloric region of the stomach were stained with hematoxylin and eosin (H & E) and periodic acid-Schiff (PAS). Immunohistochemical staining was performed for inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) levels were measured biochemically. By light microscopy, we observed loss of gastric epithelial cells and greater polymorphonuclear cell migration into the mucosa in the CS group compared to the C group. We found intact epithelial cell structure and a thick superficial mucus layer in the CS + FA group compared to the CS group. These findings in the CS + FA group were similar to those for group C. iNOS staining was stronger in the CS group compared to the C group. TOS and OSI levels in the CS + FA group were decreased compared to the CS group, but TAS, SOD, GPx and CAT levels were increased. We found that WAS caused damage to epithelium and connective tissue of the stomach mucosa and that this damage was prevented by FA. Therefore, administration of FA appears to prevent stress induced damage to rat stomach. [ABSTRACT FROM AUTHOR]