The Intervention of tert-Butylhydroquinone Protects Ethanol-Induced Gastric Ulcer in Type-II Diabetic Rats: Role of Nrf2 pathway.

Ethanol consumption increases the prevalence of gastric ulcer (GU) in rats with type 2 diabetes (T2D). Induction of GU by absolute ethanol (5 mL/kg or 3.94 g/kg) in the animal model resembles human ulcer characteristics. The aim was to investigate the role of the Nrf2 pathway in the treatment of GU in diabetic condition. The rats were exposed to absolute ethanol before one hour of sacrifice and T2D was induced by combined exposure of high-fat diet and low dose streptozotocin. Pre-treatment of tBHQ (25 and 50 mg/kg), metformin (500 mg/kg) and omeprazole (20 mg/kg) were given once daily for last three consecutive weeks. In ethanol-exposed diabetic rats, pretreatment with tBHQ, omeprazole, and metformin reduced gastric mucosal lesion, ulcer index, histological alterations, MDA level and apoptosis. Further, the intervention of tBHQ, omeprazole and metformin improved the integrity of the stomach mucosa, glutathione, gastric pH, collagen and goblet cells. tBHQ treatment improved ethanol-induced alterations of Nrf2, catalase, HSP70, NF-κB and endothelin-1 expressions in diabetic rats. In diabetic conditions, the incidence of GU is increased due to elevated levels of ROS, inflammatory mediators, depleted levels of cellular antioxidants, altered gastric parameters. The tBHQ intervention could be a rational strategy to protect these changes.