The dual modulatory effect of folic acid supplementation on indomethacin-induced gastropathy in the rat.

BACKGROUND/AIMS Folic acid modulates several disorders in humans. We investigated the effects of folic acid supplementation at varying doses on ulcer formation in the rat. MATERIALS AND METHODS Male Wistar rats were treated with 1 mg/kg, 2 mg/kg and 3 mg/kg diet of folic acid for 21 days. Gastric ulceration was induced by indomethacin, scored, and assayed to determine the concentration of mucus, malondialdehyde, catalase, and superoxide dismutase in homogenized samples. Normal saline- and ranitidine-treated groups served as negative and positive control, respectively. RESULTS Indomethacin caused severe damage to the glandular portion of the rats' stomachs with increase in malondialdehyde concentration and reduction in mucus, catalase and superoxide dismutase concentration (p < 0.001). Folic acid supplementation at 2 mg/kg diet reduced significantly the formation of gastric lesions by indomethacin, while at 3 mg/kg, potentiation of the lesions was observed (p < 0.05). Malondialdehyde concentration significantly decreased and superoxide dismutase activity increased in the 2 mg/kg folic acid pre-treated group, while 3 mg/kg folic acid significantly increased the malondialdehyde concentration and decreased both catalase and superoxide dismutase. Mucus concentration was increased in the 2 mg/kg folic acid pretreated group, but decreased in the 3 mg/kg folic acid pretreated group when compared with controls. Pre-treatment with 1 mg/kg diet of folic acid produced no significant changes. Histopathological studies underlined differences in the indomethacin-induced alterations in gastric mucosal structure following pre-treatment with a 2 mg/kg or 3 mg/kg diet of folic acid. CONCLUSIONS Folic acid is gastroprotective at the basal requirement supplemental dose; high dose may be dangerous to the integrity of the stomach.