title: Effects of statins on liver cell function and inflammation in septic rats.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Aline Maria
authors.initials: AM
authors.lastname: Stolf
authors.forename: Francislaine dos Reis
authors.initials: Fdos R
authors.lastname: Lívero
authors.forename: Arturo Alejandro
authors.initials: AA
authors.lastname: Dreifuss
authors.forename: Amanda Leite
authors.initials: AL
authors.lastname: Bastos-Pereira
authors.forename: Isabella Aviles
authors.initials: IA
authors.lastname: Fabosi
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Alves de Souza
authors.forename: Liana de Oliveira
authors.initials: Lde O
authors.lastname: Gomes
authors.forename: Raphaella
authors.initials: R
authors.lastname: Chicorski
authors.forename: Anna Paula
authors.initials: AP
authors.lastname: Brandt
authors.forename: Silvia Maria Suter
authors.initials: SM
authors.lastname: Cadena
authors.forename: José Ederaldo Queiroz
authors.initials: JE
authors.lastname: Telles
authors.forename: Aline Borsato
authors.initials: AB
authors.lastname: Hauser
authors.forename: Ronald Oude
authors.initials: RO
authors.lastname: Elferink
authors.forename: Aleksander Roberto
authors.initials: AR
authors.lastname: Zampronio
authors.forename: Alexandra
authors.initials: A
authors.lastname: Acco
mesh_terms: D000818:Animals; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1