The intervention of tert-butylhydroquinone protects ethanol-induced gastric ulcer in type II diabetic rats: the role of Nrf2 pathway

Ethanol consumption increases the prevalence of gastric ulcer (CU) in rats with type II diabetes (T2D). Induction of CU 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 nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the treatment of GU in diabetic condition. The rats were exposed to absolute ethanol 1 h before sacrifice and T2D was induced by combined exposure of high-fat diet and low dose streptozotocin. Pretreatment of tert-butylhydroquinone (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, malondialdehyde level, and apoptosis. Furthermore, the intervention of tl3HQ, 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, heat shock protein 70 (HSP70), NF-kappa B, and endothelin-1 expressions in diabetic rats. In diabetic conditions, the incidence of GU is increased due to elevated levels of reactive oxygen species, inflammatory mediators, depleted levels of cellular antioxidants, and altered gastric parameters. The tBHQ intervention could be a rational strategy to protect these changes.

Automated summary

The study found that ethanol consumption increases the prevalence of gastric ulcers in rats with type II diabetes, but intervention with tBHQ can reduce ethanol-induced ulceration and improve gastric mucosal structure and integrity.