Fluvastatin ameliorates endotoxin induced multiple organ failure in conscious rats.

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-alpha (TNF-alpha), 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 1mg/kg fluvastatin followed 10min later, by an intravenous injection of 10mg/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-alpha, interleukin-10 and nitric oxide.

RESULTS:

LPS significantly increased blood TG, BUN, Cre, LDH, CPK, GOT, GPT, TNF-alpha, 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-alpha 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-alpha, 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.

• Authors: Chung-Hua Chen, Ru-Ping Lee, Wen-Tien Wu, Kuang-Wen Liao, Nanly Hsu, Bang-Gee Hsu
• Journal: Resuscitation (Resuscitation) Vol. 74 Issue 1 Pg. 166-74 (Jul 2007) ISSN: 0300-9572 [Print] Ireland
• PMID: 17353078 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fatty Acids, Monounsaturated
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Indoles
• Lipopolysaccharides
• Triglycerides
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Nitric Oxide
• Fluvastatin
• Cholesterol
• Creatinine
• L-Lactate Dehydrogenase
• Aspartate Aminotransferases
• Alanine Transaminase
• Creatine Kinase

Topics

• Alanine Transaminase (blood)
• Analysis of Variance
• Animals
• Aspartate Aminotransferases (blood)
• Blood Urea Nitrogen
• Cholesterol (blood)
• Creatine Kinase (blood)
• Creatinine (blood)
• Enzyme-Linked Immunosorbent Assay
• Fatty Acids, Monounsaturated (administration & dosage, pharmacology)
• Fluvastatin
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage, pharmacology)
• Indoles (administration & dosage, pharmacology)
• Injections, Intravenous
• Interleukin-10 (blood)
• L-Lactate Dehydrogenase (blood)
• Lipopolysaccharides
• Male
• Multiple Organ Failure (blood, drug therapy)
• Nitric Oxide (blood)
• Rats
• Rats, Wistar
• Triglycerides (blood)
• Tumor Necrosis Factor-alpha (blood)