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Lithium exacerbates hepatic ischemia/reperfusion injury by inhibiting GSK-3β/NF-κB-mediated protective signaling in mice.
MedLine Citation:
PMID:  23051669     Owner:  NLM     Status:  Publisher    
Lithium (an inhibitor of GSK-3β activity) has beneficial effects on ischemia/reperfusion (I/R) injury in the central nervous system, heart and kidney. However, the role of lithium in hepatic I/R injury is unknown. The aim of this study was to assess the effects of lithium on hepatic I/R injury in a mouse model of partial hepatic I/R. Previous studies showed that lithium chloride (LiCl) can phosphorylate residue Ser9, inhibit GSK-3β activity, and improve I/R injury in other organs. In the present study, mice were pretreated with either vehicle or LiCl, which had similar effects on GSK-3β activity. Surprisingly, treatment with LiCl significantly exacerbated hepatic I/R injury, which was determined by serological and histological analyses. Acute and chronic LiCl treatment caused serious damage in hepatic I/R injury, including increased apoptosis and oxidative stress. To gain insight into the mechanism involved in this damage, the activity of nuclear factor-κB (NF-κB) (GSK-3β can regulate the transcriptional complex of NF-κB) was analyzed, which revealed that LiCl treatment significantly down-regulated the activity of NF-κB. The NF-κB-mediated protective genes were then further evaluated, including anti-apoptotic genes (RAF2, cIAP 2, Bfl-1 and cFLIP) and the antioxidant gene MnSOD. The expression of these protective genes was obviously suppressed compared with the vehicle group. Taken together, these findings show that lithium exacerbates hepatic I/R injury by suppressing the expression of GSK-3β/NF-κB-mediated protective genes.
Yongxiang Xia; Jianhua Rao; Aihua Yao; Feng Zhang; Guoqiang Li; Xuehao Wang; Ling Lu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-7
Journal Detail:
Title:  European journal of pharmacology     Volume:  -     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Living Donor Liver Transplantation of Ministry of Public Health, Nanjing 210029, China.
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