The Role of Zileuton in Indomethacin- Induced Gastric Ulceration in Pyloric-Ligated Diabetic Rats

Zileuton is an active inhibitor of 5-lipoxygenase, it also inhibits leukotrienes (LTB4, LTC4, LTD4, and LTE4) formation. It has antioxidant and anti-inflammatory properties which renders it an attractive candidate for protection against peptic ulcer. Therefore, this study was performed to assess the protective property of this agent against indomethacin (IND)-induced gastric ulceration in diabetic rats. A total of 36 adult male albino rats were used in the study and divided into 6 groups (6 rats each) into the following groups: normal control group, diabetic control group, diabetic IND group (single intraperitoneal injection of 30 mg/kg), diabetic IND/ omeprazole-treated group (40 mg/kg/day), diabetic IND/ zileuton-treated group (25mg/kg/day), diabetic IND/ omeprazole/ zileuton-treated group. The treated drugs were administered 14 days before pyloric ligation and IND administration to the diabetic rats. Zileuton pretreatment significantly attenuated the gastric mucosal lesions induced by IND administration, decreased the total gastric acidity, and pepsin activity with marked attenuation of the gastric mucosal lipid peroxidation and serum tumor necrosis factor alpha. In addition, zileuton pretreatment significantly increased the activity of both catalase and superoxide dismutase, gastric mucosal levels of nitric oxide and the concentration of mucin in gastric juice in comparison to the diabetic indomethacin-treated rats. Furthermore, zileuton pretreatment had antiapoptotic effect as evident by immunological study of caspase 3. In conclusion, zileuton can be considered a potential therapeutic agent to protect against the major clinical challenge of gastric injury in diabetic rats.