Protective effect of magnesium on indomethacin-induced gastric ulcer in mice

Gastric ulcer disease is a common problem of the gastrointestinal tract, with increasing incidence and prevalence attributed to a loss of balance between aggressive and protective factors. Gastric ulcer is a chronic condition characterized by damage to the mucosal, submucosal, and muscular layers of the stomach, primarily caused by excessive secretion of gastric acid, pepsin, and other digestive enzymes. The role of antioxidants in promoting ulcer healing is well established. Magnesium (Mg), being a main macro element, exhibits various beneficial effects, including antioxidant, analgesic, anti-inflammatory, antidiabetic, antacid, anti-apoptotic, and free radical-scavenging properties. In this study, we investigated the effect of magnesium sulfate (MgSO₄) on indomethacin-induced gastric ulcers in male Balb/c mice. The effect of orally administered MgSO₄ (0.05, 0.1, and 0.2 g/kg) was assessed in both gastric ulcer and healthy mice. The animals were randomly assigned to 10 groups: healthy control; sham; MgSO₄ alone at 0.05, 0.1, or 0.2 g/kg; gastric ulcer control (indomethacin, 18 mg/kg); MgSO₄ at 0.05, 0.1, or 0.2 g/kg) plus indomethacin; and omeprazole (20 mg/kg) plus indomethacin. Treatment were administered intragastrically for 14 consecutive days. All mice underwent a 24-h fasting period before the final day of treatment. Six hours after the last dose, indomethacin was administered orally to induce gastric ulceration. The mice were then sacrificed for histopathological and biochemical assessments. Administration of MgSO₄ significantly reduced the ulcerated area, decreased malondialdehyde (MDA) levels, and increased gastric antioxidative enzyme activity, consistent with histopathological evidence of mucosal protection. In ulcer-induced mice, MgSO₄ significantly decreased the expression of Epidermal Growth Factor (EGF), 70-kDa Heat Shock Protein (HSP-70), and Spasmolytic Polypeptide (SP) expression in the gastric tissue. In conclusion, magnesium may act as an anti-ulcerogenic and gastroprotective agent in mice.