xanthohumol and Chemical-and-Drug-Induced-Liver-Injury

Acetaminophen (APAP) is one of the world's popular and safe painkillers, and overdose can cause severe liver damage and even acute liver failure. The effect and mechanism of the xanthohumol on acetaminophen-induced hepatotoxicity remains unclear.. The hepatoprotective effects of xanthohumol were studied using APAP-induced HepG2 cells and acute liver injury of mouse, seperately.. Thus, xanthohumol exerted a hepatoprotective effect by inhibiting oxidative stress and mitochondrial dysfunction through the AMPK/Akt/GSK3β/Nrf2 antioxidant pathway.

Topics: Acetaminophen; AMP-Activated Protein Kinases; Animals; Chemical and Drug Induced Liver Injury; Glycogen Synthase Kinase 3 beta; Hydrogen Peroxide; Liver; Mice; NF-E2-Related Factor 2; Oxidative Stress; Proto-Oncogene Proteins c-akt; Signal Transduction

Xanthohumol (XN), a prenyl flavonoid present in beer, prevents the acute hepatic injury induced by carbon tetrachloride (CCl4) in rats. Pre-treatment of rats with XN significantly reduced the increased liver weight observed in CCl4-intoxicated rats, normalised the increased values of plasma lactate dehydrogenase, glutamate oxaloacetate transaminase and glutamate pyruvate transaminase activities and reduced the incidence of histopathological alterations produced by CCl4. The oxidative stress induced by CCl4 administration elicited a significant decrease in the levels of reduced glutathione as well as an increase in thiobarbituric acid reactive substances (TBARS) and H2O2 concentrations. Pre-treatment of rats with XN resulted in a significant (p<0.05) increase in reduced glutathione (GSH) content and a reduction in TBARS and H2O2 concentrations to their normal values. XN pre-treatment also prevented the significant reductions of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase activities observed in CCl4-treated rats compared to control animals. Our results suggest that the hepatoprotective effect of XN is based on its antioxidant properties as well as it being an efficient inhibitor of lipid peroxidation and a protector against the degradation of antioxidant enzymes induced by CCl4 intoxication.

Topics: Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Flavonoids; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Liver; Molecular Structure; Oxidants; Propiophenones; Rats; Rats, Wistar