الفهرس | Only 14 pages are availabe for public view |
Abstract Acetaminophen (APAP) overdose accounts for most of the acute liver failure cases where, APAP hepatotoxicity results in hepatocellular death and a sterile inflammatory response which is mediated by the NLRP3-inflammasome. APAP- induced hepatocellular injury is characterized by high plasma levels of ALT, AST, and LDH. Moreover, the results of HE stainings indicated that APAP insult led to hepatocellular death. APAP also results in the depletion of GSH as well as SOD through the excessive production of the highly reactive toxic metabolite N-acetyl-para-benzoquinone imine (NAPQI).In our study, we aimed to examine the effect of celastrol (NF-ĸB inhibitor), Brilliant Blue G (P2X7 antagonist) and their combination on APAP- induced hepatotoxicity in mice. The results indicated that both celastrol and BBG pretreatments, especially when combined together, curbed APAP-induced hepatocellular injury (ALT, AST and LDH) and death (necrosis and apoptosis), prevented the consumption of hepatic antioxidants (GSH and SOD), attenuated the inflammatory cells accumulation in the liver, and enhanced the reparative capacity of injured hepatocytes. In conclusion, this study elicits clinical applicability and therapeutic utility of celastrol and BBG combination in human cases of APAP-overdose hepatotoxicity. |