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Fluvastatin ameliorates endotoxin induced multiple organ failure in conscious rats.
Resuscitation. 2007 Jul; 74(1):166-74.R

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+Show Affiliations

Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17353078

Citation

Chen, Chung-Hua, et al. "Fluvastatin Ameliorates Endotoxin Induced Multiple Organ Failure in Conscious Rats." Resuscitation, vol. 74, no. 1, 2007, pp. 166-74.
Chen CH, Lee RP, Wu WT, et al. Fluvastatin ameliorates endotoxin induced multiple organ failure in conscious rats. Resuscitation. 2007;74(1):166-74.
Chen, C. H., Lee, R. P., Wu, W. T., Liao, K. W., Hsu, N., & Hsu, B. G. (2007). Fluvastatin ameliorates endotoxin induced multiple organ failure in conscious rats. Resuscitation, 74(1), 166-74.
Chen CH, et al. Fluvastatin Ameliorates Endotoxin Induced Multiple Organ Failure in Conscious Rats. Resuscitation. 2007;74(1):166-74. PubMed PMID: 17353078.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fluvastatin ameliorates endotoxin induced multiple organ failure in conscious rats. AU - Chen,Chung-Hua, AU - Lee,Ru-Ping, AU - Wu,Wen-Tien, AU - Liao,Kuang-Wen, AU - Hsu,Nanly, AU - Hsu,Bang-Gee, Y1 - 2007/03/13/ PY - 2006/09/13/received PY - 2006/11/28/revised PY - 2006/12/04/accepted PY - 2007/3/14/pubmed PY - 2007/9/14/medline PY - 2007/3/14/entrez SP - 166 EP - 74 JF - Resuscitation JO - Resuscitation VL - 74 IS - 1 N2 - 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. SN - 0300-9572 UR - https://www.unboundmedicine.com/medline/citation/17353078/Fluvastatin_ameliorates_endotoxin_induced_multiple_organ_failure_in_conscious_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-9572(06)00786-6 DB - PRIME DP - Unbound Medicine ER -