Tacrine, an oral acetylcholinesterase inhibitor, induced hepatic oxidative damage, which was blocked by liquiritigenin through GSK3-beta inhibition

Biological & Pharmaceutical Bulletin
Sang Mi ParkYoung Woo Kim

Abstract

Although the cholinesterase inhibitor tacrine has been successfully used for the 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 the toxic effect of tacrine on hepatocytes and the beneficial effect of LQ on tacrine intoxication in vivo and in vitro, and the underlying mechanism involved. In hepatocyte cell lines, tacrine induced cell death and oxidative stress, as indicated by decreases in cell viability and glutathione (GSH) contents, which were blocked by pretreatment with LQ. Fluorescent activated cell sorter (FACS) analysis revealed that LQ inhibited cellular H2O2 production and mitochondrial dysfunction induced by tacrine in HepG2 cells. Furthermore, LQ promoted inhibitory phosphorylation of glycogen synthase kinase-3β (GSK3β) and prevented decreases in GSK3β phosphorylation induced by tacrine. In rats treatment with tacrine at 30 mg/kg increased hepatic damage as assessed by blood biochemistry and histopathology. Administration of LQ (10 or 30 mg/kg/d, per os (p.o.)) or the hepatoprotective drug sylimarin (100 mg/kg/d) for 3 d inhibited elevations in alanine ami...Continue Reading

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Citations

Nov 4, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ai-Song Yu, Lin Zhao
May 6, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Ji Yun JungSang Chan Kim
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Nov 2, 2019·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Bernard Fromenty

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