Effects of simvastatin in abdominal sepsis in rats.
OBJECTIVE
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 eight Wistar rats weighing 285+/-12 g were randomly divided in: CLP/Sinvastatin rats (n=7), treated with 10 mg/Kg of oral simvastatin 18 and 2 hs before 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+/-42 pg/mL; 46.3+/-18 pg/mL and 28.4+/-13 pg/mL in CLP/Sinvastatin rats, significantly lower (p<0.05) than in group CLP/Saline (778.5+/-86 pg/ml; 176.9+/-46 pg/ml; 133.6+/-21 pg/ml, respectively). The same results were observed in total leukocytes and neutrophils counts.


CONCLUSIONS
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.
Souza Neto
José Luiz de
JL
Program in Health Sciences, UFRN, Brazil.
Araújo Filho
Irami
I
Rego
Amália Cínthia Meneses do
AC
Dominici
Víctor Almeida
VA
Azevedo
Italo Medeiros
IM
Egito
Eryvaldo Sócrates Tabosa
ES
Brandão-Neto
José
J
Medeiros
Aldo Cunha
AC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002432:Cecum / Q000601:surgery; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects; D008214:Lymphocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D019821:Simvastatin / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019821:Simvastatin