Glibenclamide protects against thioacetamide-induced hepatic damage in Wistar rat: investigation on NLRP3, MMP-2, and stellate cell activation

Glibenclamide (GLB), most widely used in the treatment of type II diabetes mellitus, inhibits K-ATP(+) channel in pancreatic- 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 (200mg/kg, ip, twice weekly) and GLB (1.25, 2.5, and 5mg/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-1, -SMA, NLRP3, ASC, caspase-1, and IL-1, 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.