Tacrine, an Oral Acetylcholinesterase Inhibitor, Induced Hepatic Oxidative Damage, Which Was Blocked by Liquiritigenin through GSK3-beta Inhibition

摘要: Although the cholinesterase inhibitor tacrine has been successfully used for treatment of Alzheimer's disease, it is known to have hepatotoxic effects. Liquiritigenin (LQ), an active flavonoid in Glycyrrhizae radix, exerts protective effects against liver damage. This study investigated toxic effect on hepatocytes and beneficial LQ intoxication vivo vitro, underlying mechanism involved. In hepatocyte cell lines, induced death oxidative stress, as indicated by decreases viability glutathione (GSH) contents, which were blocked pretreatment with LQ. Fluorescent activated sorter (FACS) analysis revealed that inhibited cellular H2O2 production mitochondrial dysfunction HepG2 cells. Furthermore, promoted inhibitory phosphorylation glycogen synthase kinase-3β (GSK3β) prevented GSK3β tacrine. rats at 30 mg/kg increased hepatic damage assessed blood biochemistry histopathology. Administration (10 or mg/kg/d, per os (p.o.)) hepatoprotective drug sylimarin (100 mg/kg/d) 3 d elevations alanine aminotransferase, aspartate histological changes These results show efficaciously protects rat tacrine-induced damage, suggest a therapeutic candidate ameliorating