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J Surg Res ; 178(2): 888-97, 2012 Dec.
Article de Anglais | MEDLINE | ID: mdl-22954522

RÉSUMÉ

BACKGROUND: Several studies suggest that the presence of statins may be beneficial during sepsis, but this idea is controversial. The aim of this study was to investigate the effects of long-term statin treatment in the livers of septic animals, focusing on its antioxidant, antiinflammatory, and metabolic properties. MATERIALS AND METHODS: Male Wistar rats were treated orally with simvastatin, atorvastatin, or vehicle once a d. After 30 d, sepsis was induced by cecal ligation and puncture (CLP) in Control, Simvastatin-treated, and Atorvastatin-treated groups, while the Sham group underwent only laparotomy. The Basal Simvastatin and Basal Atorvastatin groups received only their respective drugs without surgery. Twenty-four h after CLP or laparotomy, samples were collected from anesthetized rats for evaluation of hepatic oxidative stress, liver histology, hepatic mitochondria enzyme activity, leukocyte counts in blood and peritoneal cavity, gene expression of hepatic superoxide dismutase and TNF-2, and plasma biochemistry. RESULTS: Most parameters that we tested exhibited expected changes upon sepsis induction. However, statin treatment only improved liver mitochondrial enzymatic activity. In other parameters, simvastatin and atorvastatin failed to protect the liver against injuries incurred upon the CLP-induced polymicrobial sepsis model. CONCLUSIONS: Pretreatment with simvastatin or atorvastatin alone before sepsis induction improved mitochondrial activity in the liver; however, this result was not reproduced in other biomarkers of liver function and leukocyte migration during sepsis. Future studies should be performed to evaluate whether statins can be combined with other drugs to increase the efficacy of sepsis therapy.


Sujet(s)
Hépatocytes/effets des médicaments et des substances chimiques , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/pharmacologie , Inflammation/traitement médicamenteux , Sepsie/traitement médicamenteux , Animaux , Hépatocytes/anatomopathologie , Hépatocytes/physiologie , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/usage thérapeutique , Mâle , Stress oxydatif/effets des médicaments et des substances chimiques , Rats , Rat Wistar , Sepsie/métabolisme , Sepsie/anatomopathologie , Superoxide dismutase/génétique , Superoxide dismutase-1 , Facteur de nécrose tumorale alpha/génétique
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