Gastric ulcer (GU) is the most common health concern that occurs due to alcohol consumption, smoking and physiological stress. Ethanol-induced GU in animal model resembles the pathophysiology of human ulcer. The present study was designed to investigate the cytoprotective and anti-inflammatory properties of tert-butylhydroquinone (tBHQ), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, against gastric mucosal damage induced by acute exposure of ethanol (5 ml/kg). The intervention of tBHQ (25 and 50 mg/kg, per os (po)) and omeprazole (20 mg/kg, po) was done for 10 consecutive days. Omeprazole was chosen as a standard drug because it is prescribed for the treatment of GU. Pretreatment of tBHQ decreased gastric mucosal lesion, ulcer index, apoptotic cells and lipid peroxidation level induced by ethanol. Furthermore, the intervention of tBHQ increased gastric mucosa integrity, pH, reduced glutathione, collagen and mucus-producing goblet cells. Intervention of tBHQ increased the expression of antioxidant markers such as Nrf2, haeme oxygenase-1 and catalase and decreased the expressions of inflammatory markers such as nuclear factor kappa-light-chain-enhancer of activated B cells and cyclooxygenase-2. The cytoprotective potential of tBHQ against gastric mucosal damage might be due to its ability to enhance cellular antioxidants and anti-inflammatory responses.

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Glibenclamide (GLB), most widely used in the treatment of type II diabetes mellitus, inhibits K channel in pancreatic-β cells and releases insulin, while thioacetamide (TAA) is a well-known hepatotoxicant and most recommended for the induction of acute and chronic liver disease. The purpose of this study was to evaluate the hepatoprotective potential of GLB against TAA-induced hepatic damage in Wistar rats. TAA (200 mg/kg, ip, twice weekly) and GLB (1.25, 2.5, and 5 mg/kg/day, po) were administered for 6 consecutive weeks. Different biochemical, DNA damage, histopathological, TEM, immunohistochemical, and western blotting parameters were evaluated. GLB treatment has no effects on the TAA-induced significant decrease in body and liver weights. TAA treatment significantly increased liver index and treatment with GLB has no effect the same. TAA treatment altered the liver morphology, whereas treatment with GLB normalized the alteration in morphology. Further, significant increase in oxidative stress, apoptosis, and DNA damage was found in TAA-treated animals and GLB treatment significantly reduced these effects. TAA-induced plasma transaminases and serum ALP levels were significantly restored by GLB. Furthermore, histopathological findings showed the presence of lymphocyte infiltration, collagen deposition, bridging fibrosis, degeneration of portal triad, and necrosis in TAA-treated animals and GLB intervention significantly reduced the same. TEM images revealed that GLB significantly normalized the hepatic stellate cell morphology as well as restored the number of lipid droplets. GLB treatment significantly downregulated the expressions of TGF-β1, α-SMA, NLRP3, ASC, caspase-1, and IL-1β, and upregulated MMP-2 and catalase against TAA-induced liver damage. The outcomes of the present study confirmed that GLB ameliorated the liver damage induced by TAA.

The present study was designed to investigate the hepatoprotective potential of dimethyl fumarate (DMF) against thioacetamide (TAA)‐induced liver damage. Wistar rats were treated with DMF (12.5, 25, and 50 mg/kg/day, orally) and TAA (200 mg/kg intraperitoneally, every third day) for 6 consecutive weeks. TAA exposure significantly reduced body weight, increased liver weight and index, and intervention with DMF did not ameliorate these parameters. DMF treatment significantly restored TAA‐induced increase in the levels of aspartate aminotransferase, alanine aminotransferase, γ‐glutamyl transferase, total bilirubin, uric acid, malondialdehyde, reduced glutathione, and histopathological findings such as inflammatory cell infiltration, deposition of collagen, necrosis, and bridging fibrosis. DMF treatment significantly ameliorated TAA‐induced hepatic stellate cell activation, increase in inflammatory cascade markers (NACHT, LRR, and PYD domains‐containing protein 3; NLRP3, apoptosis‐associated speck like protein containing a caspase recruitment domain; ASC, caspase‐1, nuclear factor‐kappa B; NF‐κB, interleukin‐6), fibrogenic makers (α‐smooth muscle actin; ɑ‐SMA, transforming growth factor; TGF‐β1, fibronectin, collagen 1) and antioxidant markers (nuclear factor (erythroid‐derived 2)‐like factor 2; Nrf2, superoxide dismutase‐1; SOD‐1, catalase). The present findings concluded that DMF protects against TAA‐induced hepatic damage mediated through the downregulation of inflammatory cascades and upregulation of antioxidant status.

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