Fluvastatin ameliorates endotoxin induced multiple organ failure in conscious rats

Chung Hua Chen, Ru Ping Lee, Wen Tien Wu, Kuang-Wen Liao, Nanly Hsu, Bang Gee Hsu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Objectives: Sepsis is a severe inflammatory disorder that may lead to multiple organ failure. Lipopolysaccharide (LPS) is associated with Gram-negative sepsis and can activate monocytes and macrophages to release pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α), nitric oxide (NO) and anti-inflammatory mediator such as interleukin-10 (IL-10). In this present study, we used fluvastatin, a HMG-CoA reductase inhibitor, to study its effects upon LPS-induced endotoxic shock in conscious rats. Methods: The experiments were designed that rats received an intravenous injection of 1 mg/kg fluvastatin followed 10 min later, by an intravenous injection of 10 mg/kg Klebsiella pneumoniae LPS, the latter inducing endotoxic shock amongst conscious rats. Subsequently, the levels of certain biochemical variables and cytokines in serum were then measured during the ensuing 48-h period following sepsis. These included total cholesterol (TCH), triglyceride (TG), blood urea nitrogen (BUN), creatinine (Cre), creatine phosphokinase (CPK), lactic dehydrogenase (LDH), aspartate transferase (GOT), alanine transferase (GPT), tumor necrosis factor-α, interleukin-10 and nitric oxide. Results: LPS significantly increased blood TG, BUN, Cre, LDH, CPK, GOT, GPT, TNF-α, IL-10 and NO levels but decreased the blood TCH level. Pretreatment of test rats with fluvastatin decreased blood levels of certain markers of organ injury, suppressed the release of TNF-α and increased IL-10, and NO levels following LPS treatment. Fluvastatin did not affect the blood TCH and TG level subsequent to the development of sepsis. Conclusions: Pre-treatment with fluvastatin suppresses the release of plasma TNF-α, increases plasma IL-10, and NO production, and decreases the levels of markers of organ injury associated with endotoxic shock, so ameliorating LPS-induced organ damage amongst conscious rats.

Original languageEnglish
Pages (from-to)166-174
Number of pages9
JournalResuscitation
Volume74
Issue number1
DOIs
StatePublished - 1 Jul 2007

Keywords

  • Fluvastatin
  • Hypotension
  • Nitric oxide
  • Septic shock

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