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

• Published in: Canadian journal of physiology and pharmacology Vol. 99; no. 5; pp. 522 - 535
• Main Authors: Rahman, Ziaur, Dwivedi, Durgesh Kumar, Jena, G.B
• Format: Journal Article
• Language: English
• Published: 1840 Woodward Drive, Suite 1, Ottawa, ON K2C 0P7 NRC Research Press 01.05.2021; Canadian Science Publishing NRC Research Press
• Subjects: Alcohol; Alcohol, Denatured; Animal models; Animals; Anti-Ulcer Agents - pharmacology; Anti-Ulcer Agents - therapeutic use; Antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Apoptosis; Apoptosis - drug effects; Care and treatment; Catalase; Causes of; Collagen; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - chemically induced; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; diabète sucré de type II; Dosage; Endothelin 1; Endothelins; Ethanol; Ethanol - adverse effects; Ethanol - toxicity; Gastric Mucosa - drug effects; Gastric Mucosa - metabolism; Gastric Mucosa - pathology; gastric ulcer; Glutathione; Goblet cells; Health aspects; Heat shock proteins; High fat diet; Hsp70 protein; Hydroquinone; Hydroquinones - pharmacology; Hydroquinones - therapeutic use; Inflammation; Low fat diet; Male; Malondialdehyde; Metformin; Metformin - pharmacology; Metformin - therapeutic use; Mucosa; NF-E2-Related Factor 2 - metabolism; NF-κB protein; Nrf2; Nutrient deficiency; Omeprazole; Oxidative Stress - drug effects; pH effects; Physiological aspects; Prevention; Rats; Rats, Wistar; Reactive oxygen species; Rodents; Signal Transduction - drug effects; Stomach ulcer; Stomach Ulcer - chemically induced; Stomach Ulcer - drug therapy; Stomach Ulcer - metabolism; Stomach Ulcer - pathology; Stomach Ulcer - prevention & control; t-Butylhydroquinone; tert-butylhydroquinone; Transcription factors; Type 2 diabetes; type II diabetes mellitus; Ulcers; ulcère gastrique; Canada; tert-butylhydroquinone; type II diabetes mellitus; Nrf2; gastric ulcer; ethanol; ulcère gastrique; diabète sucré de type II
• ISSN: 0008-4212; 1205-7541; 1205-7541
• DOI: 10.1139/cjpp-2020-0173

Ethanol consumption increases the prevalence of gastric ulcer (GU) in rats with type II 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 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 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, heat shock protein 70 (HSP70), NF-κB, 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.