Document Detail

Long-term simvastatin attenuates lung injury and oxidative stress in murine acute lung injury models induced by oleic Acid and endotoxin.
MedLine Citation:
PMID:  21396178     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors have several pleiotropic effects, including anti-inflammatory properties, and are reported to improve endothelial functions. Pathophysiologically, acute lung injury (ALI) is caused by a severe inflammatory response and endothelial dysfunction.
OBJECTIVE: To investigate the effects of simvastatin (an HMG-CoA reductase inhibitor) on oxidative stress and lung histopathology in 2 murine models of ALI, induced by oleic acid and endotoxin.
METHODS: The mice were randomly divided into 2 groups: one received 2 mg/kg/d intraperitoneal simvastatin for 15 days. Then the groups were further divided into 3, which received saline, oleic acid, or endotoxin. Four hours after inducing ALI we obtained lung samples for histopathology analysis, myeloperoxidase, glutathione, and malondialdehyde measurement, and blood samples for malondialdehyde measurement.
RESULTS: Endotoxin and oleic acid lung injury increased tissue myeloperoxidase (P = .009 for both), decreased tissue glutathione (P = .02 and P = .009, respectively), and increased tissue malondialdehyde (P = .009 for both), compared to the control group. Simvastatin decreased myeloperoxidase only in the oleic acid group (P = .01). Simvastatin increased glutathione (P = .005 and P = .003, respectively) and lowered malondialdehyde in both the endotoxin and oleic acid groups (P = .003 for both). Histopathology revealed that simvastatin protected the lung tissue in both ALI models, but the protection was greater in the endotoxin group.
CONCLUSIONS: Pretreatment with simvastatin decreased the severity of ALI in oleic acid and endotoxin ALI models, by decreasing inflammation and oxidative stress.
Neriman Defne Altintas; Pergin Atilla; Alper Bektas Iskit; Arzu Topeli
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2011-03-09
Journal Detail:
Title:  Respiratory care     Volume:  56     ISSN:  0020-1324     ISO Abbreviation:  Respir Care     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-01     Completed Date:  2011-09-20     Revised Date:  2012-03-06    
Medline Journal Info:
Nlm Unique ID:  7510357     Medline TA:  Respir Care     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1156-63     Citation Subset:  IM    
Medical Intensive Care Unit, Department of Internal Medicine, Hacettepe University, Ankara, Turkey.
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MeSH Terms
Acute Lung Injury / chemically induced,  drug therapy,  metabolism*
Disease Models, Animal
Dose-Response Relationship, Drug
Endotoxins / toxicity
Follow-Up Studies
Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
Injections, Intraperitoneal
Oleic Acid / toxicity
Oxidative Stress / drug effects*
Simvastatin / administration & dosage*
Time Factors
Reg. No./Substance:
0/Endotoxins; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 112-80-1/Oleic Acid; 79902-63-9/Simvastatin
Comment In:
Respir Care. 2012 Feb;57(2):331; author reply 331-2   [PMID:  22304804 ]

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

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