Document Detail

Simvastatin protects hepatocytes from apoptosis by suppressing the TNF-α/caspase-3 signaling pathway in mice with burn injury.
MedLine Citation:
PMID:  23275311     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To investigate the liver cellular apoptosis in response to burn injury and find out if statin treatment can ameliorate this process. The hypothesis is that statin may modulate apoptosis-related gene expression and thereby reduce hepatocytic apoptosis after burn injury.
METHODS: Mice were subjected to 30% full-thickness burn injury and then treated either with or without simvastatin. The livers were harvested for histological assessment and determinations of gene expression. To investigate the mechanism involved, tumor necrosis factor (TNF)-α and caspase-3 knockout (KO) mice were also used to evaluate the effects of burn injury and simvastatin treatment on burn-induced liver injury. The effects of simvastatin on TNF-α and caspase-3 expressions were also evaluated in cultured mouse hepatocytes.
RESULTS: Burn injury induced significant liver damage, which was indicated by striking levels of apoptosis. Simvastatin reduced the apoptotic index in the livers of mice with burn injury and this effect could be abrogated by TNF-α or caspase-3 inhibitors. Simvastatin also decreased burn-induced TNF-α and caspase-3 expression in the liver. TNF-α and caspase-3 KO mice demonstrated lower levels of apoptotic hepatocytes in response to burn, and simvastatin did not further decrease hepatocyte apoptosis in either strain of KO mice. An in vitro study demonstrated that simvastatin suppresses TNF-α and caspase-3 expression in primary cultures of mouse hepatocytes.
CONCLUSIONS: Simvastatin reduces mouse hepatocyte apoptosis by suppressing expression of the TNF-α/caspase-3 pathway.
Gaofeng Zhao; Yong-Ming Yu; Masao Kaneki; Ronald G Tompkins; Alan J Fischman
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of surgery     Volume:  257     ISSN:  1528-1140     ISO Abbreviation:  Ann. Surg.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-13     Completed Date:  2013-08-01     Revised Date:  2014-08-05    
Medline Journal Info:
Nlm Unique ID:  0372354     Medline TA:  Ann Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1129-36     Citation Subset:  AIM; IM    
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MeSH Terms
Apoptosis / drug effects*
Blotting, Western
Burns / metabolism*
Caspase 3 / metabolism*
Hepatocytes / drug effects*
Signal Transduction / drug effects*
Simvastatin / pharmacology*
Tumor Necrosis Factor-alpha / metabolism*
Grant Support
P50 21700//PHS HHS; P50 GM021700/GM/NIGMS NIH HHS; T32 GM007035/GM/NIGMS NIH HHS
Reg. No./Substance:
0/Tumor Necrosis Factor-alpha; AGG2FN16EV/Simvastatin; EC 3.4.22.-/Caspase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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