Effects of simvastatin in abdominal sepsis in rats

PURPOSE: Statins are widely recognized as hypolipemic drugs, but some studies have observed anti-inflammatory and immunomodulatory effects, known as pleiotropic. The aims of this work was to study possible anti-inflammatory effects of simvastatin in abdominal sepsis. Serum pro-inflammatory cytokines and leukocytes count were determined in an experimental model of abdominal sepsis, using cecal ligation and puncture (CLP) in rats. METHODS: Twenty eigth Wistar rats weighing 285±12g were randomly divided in: CLP/Sinvastatin rats (n=7), treated with 10 mg/Kg of oral simvastatin 18 and 2 hs berofe CLP; CLP/Saline group rats (n=7), treated with oral saline; group Sham/Simvastatin (n=7), treated with simvastatin, and group Sham/Saline (n=7), treated with saline. Serum TNF-alpha, IL-1beta and IL-6 by ELISA and total leukocytes, neutrophils, lymphocytes, and eosinophils were determined 24 hs after CLP. ANOVA and Tukey test were used considering significant p<0.05. RESULTS: It was demonstrated that serum TNF-alpha, IL-1beta and IL-6 were respectively 364,8±42pg/mL; 46,3±18pg/mL and 28,4±13pg/mL in CLP/Sinvastatin rats, significantly lower (p<0.05) than in group CLP/Saline (778,5±86pg/ml; 176,9±46pg/ml; 133,6±21 pg/ml, respectively). The same results were observed in total leukocytes and neutrophils counts. CONCLUSION: These results clearly demonstrate that simvastatin is an effective agent that reduces cytokines levels and leukocyte count in sepsis, independently of its well-known lipid-lowering effects. Thus, HMG-CoA reductase inhibitors like simvastatin have important anti-inflammatory effects in abdominal sepsis in rats.

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Main Authors: Souza Neto,José Luiz de, Araújo Filho,Irami, Rego,Amália Cínthia Meneses do, Dominici,Víctor Almeida, Azevedo,Ítalo Medeiros, Egito,Eryvaldo Sócrates Tabosa, Brandão-Neto,José, Medeiros,Aldo Cunha
Format: Digital revista
Language:English
Published: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia 2006
Online Access:http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0102-86502006001000003
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spelling oai:scielo:S0102-865020060010000032007-02-07Effects of simvastatin in abdominal sepsis in ratsSouza Neto,José Luiz deAraújo Filho,IramiRego,Amália Cínthia Meneses doDominici,Víctor AlmeidaAzevedo,Ítalo MedeirosEgito,Eryvaldo Sócrates TabosaBrandão-Neto,JoséMedeiros,Aldo Cunha Statin Inflammation Abdominal sepsis Wistar rat Cytokine Leukocyte PURPOSE: Statins are widely recognized as hypolipemic drugs, but some studies have observed anti-inflammatory and immunomodulatory effects, known as pleiotropic. The aims of this work was to study possible anti-inflammatory effects of simvastatin in abdominal sepsis. Serum pro-inflammatory cytokines and leukocytes count were determined in an experimental model of abdominal sepsis, using cecal ligation and puncture (CLP) in rats. METHODS: Twenty eigth Wistar rats weighing 285±12g were randomly divided in: CLP/Sinvastatin rats (n=7), treated with 10 mg/Kg of oral simvastatin 18 and 2 hs berofe CLP; CLP/Saline group rats (n=7), treated with oral saline; group Sham/Simvastatin (n=7), treated with simvastatin, and group Sham/Saline (n=7), treated with saline. Serum TNF-alpha, IL-1beta and IL-6 by ELISA and total leukocytes, neutrophils, lymphocytes, and eosinophils were determined 24 hs after CLP. ANOVA and Tukey test were used considering significant p<0.05. RESULTS: It was demonstrated that serum TNF-alpha, IL-1beta and IL-6 were respectively 364,8±42pg/mL; 46,3±18pg/mL and 28,4±13pg/mL in CLP/Sinvastatin rats, significantly lower (p<0.05) than in group CLP/Saline (778,5±86pg/ml; 176,9±46pg/ml; 133,6±21 pg/ml, respectively). The same results were observed in total leukocytes and neutrophils counts. CONCLUSION: These results clearly demonstrate that simvastatin is an effective agent that reduces cytokines levels and leukocyte count in sepsis, independently of its well-known lipid-lowering effects. Thus, HMG-CoA reductase inhibitors like simvastatin have important anti-inflammatory effects in abdominal sepsis in rats.info:eu-repo/semantics/openAccessSociedade Brasileira para o Desenvolvimento da Pesquisa em CirurgiaActa Cirúrgica Brasileira v.21 suppl.4 20062006-01-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0102-86502006001000003en10.1590/S0102-86502006001000003
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language English
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author Souza Neto,José Luiz de
Araújo Filho,Irami
Rego,Amália Cínthia Meneses do
Dominici,Víctor Almeida
Azevedo,Ítalo Medeiros
Egito,Eryvaldo Sócrates Tabosa
Brandão-Neto,José
Medeiros,Aldo Cunha
spellingShingle Souza Neto,José Luiz de
Araújo Filho,Irami
Rego,Amália Cínthia Meneses do
Dominici,Víctor Almeida
Azevedo,Ítalo Medeiros
Egito,Eryvaldo Sócrates Tabosa
Brandão-Neto,José
Medeiros,Aldo Cunha
Effects of simvastatin in abdominal sepsis in rats
author_facet Souza Neto,José Luiz de
Araújo Filho,Irami
Rego,Amália Cínthia Meneses do
Dominici,Víctor Almeida
Azevedo,Ítalo Medeiros
Egito,Eryvaldo Sócrates Tabosa
Brandão-Neto,José
Medeiros,Aldo Cunha
author_sort Souza Neto,José Luiz de
title Effects of simvastatin in abdominal sepsis in rats
title_short Effects of simvastatin in abdominal sepsis in rats
title_full Effects of simvastatin in abdominal sepsis in rats
title_fullStr Effects of simvastatin in abdominal sepsis in rats
title_full_unstemmed Effects of simvastatin in abdominal sepsis in rats
title_sort effects of simvastatin in abdominal sepsis in rats
description PURPOSE: Statins are widely recognized as hypolipemic drugs, but some studies have observed anti-inflammatory and immunomodulatory effects, known as pleiotropic. The aims of this work was to study possible anti-inflammatory effects of simvastatin in abdominal sepsis. Serum pro-inflammatory cytokines and leukocytes count were determined in an experimental model of abdominal sepsis, using cecal ligation and puncture (CLP) in rats. METHODS: Twenty eigth Wistar rats weighing 285±12g were randomly divided in: CLP/Sinvastatin rats (n=7), treated with 10 mg/Kg of oral simvastatin 18 and 2 hs berofe CLP; CLP/Saline group rats (n=7), treated with oral saline; group Sham/Simvastatin (n=7), treated with simvastatin, and group Sham/Saline (n=7), treated with saline. Serum TNF-alpha, IL-1beta and IL-6 by ELISA and total leukocytes, neutrophils, lymphocytes, and eosinophils were determined 24 hs after CLP. ANOVA and Tukey test were used considering significant p<0.05. RESULTS: It was demonstrated that serum TNF-alpha, IL-1beta and IL-6 were respectively 364,8±42pg/mL; 46,3±18pg/mL and 28,4±13pg/mL in CLP/Sinvastatin rats, significantly lower (p<0.05) than in group CLP/Saline (778,5±86pg/ml; 176,9±46pg/ml; 133,6±21 pg/ml, respectively). The same results were observed in total leukocytes and neutrophils counts. CONCLUSION: These results clearly demonstrate that simvastatin is an effective agent that reduces cytokines levels and leukocyte count in sepsis, independently of its well-known lipid-lowering effects. Thus, HMG-CoA reductase inhibitors like simvastatin have important anti-inflammatory effects in abdominal sepsis in rats.
publisher Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
publishDate 2006
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0102-86502006001000003
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