| Lithium exacerbates hepatic ischemia/reperfusion injury by inhibiting GSK-3β/NF-κB-mediated protective signaling in mice. | |
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MedLine Citation:
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PMID: 23051669 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Yongxiang Xia; Jianhua Rao; Aihua Yao; Feng Zhang; Guoqiang Li; Xuehao Wang; Ling Lu |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-7 |
Journal Detail:
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Title: European journal of pharmacology Volume: - ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Elsevier B.V. All rights reserved. |
Affiliation:
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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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