Tuberc Respir Dis.  2006 Oct;61(4):374-383.

The Effects of Ethyl Pyruvate on Lipopolysaccharide-induced Acute Lung Injury

• Lee SH
• Yoon DW
• Jung JY
• Lee KJ
• Kim SJ
• Lee EJ
• Kang EH
• Jung KH
• Lee SY
• Lee SY
• Kim JH
• Shin C
• Shim JJ
• In KH
• Yoo SH
• Kang KH

Abstract

BACKGROUND: Ethyl pyruvate (EP) is a derivative of pyruvate that has recently been identified by both various in vitro and in vivo studies to have antioxidant and anti-inflammatory effects. The aim of this study was to determine the effect of EP on lipopolysaccharide (LPS)-induced acute lung injury (ALI).
METHODS
5 weeks old, male BALB/c mice were used. ALI was induced by an intratracheal instillation of LPS 0.5mg/Kg/50microliter of saline. The mice were divided into the control, LPS, EP+LPS, and LPS+EP groups. In the control group, balanced salt solution was injected intraperitoneally 30 minutes before or 9 hours after the intratracheal instillation of saline. In the LPS group, a balanced salt solution was also injected intraperitoneally 30 minutes before or 9 hours after instillation the LPS. In the EP+LPS group, 40mg/Kg of EP was injected 30 minutes before LPS instillation. In the LPS+EP group, 40mg/Kg of EP was injected 9 hours after LPS instillation. The TNF-alpha and IL-6 concentrations in the bronchoalveolar lavage fluid (BALF), and that of NF-KappaB in the lung tissue were measured in the control, LPS and EP+LPS groups at 6 hours after instillation of saline or LPS, and the ALI score and myeloperoxidase (MPO) activity were measured in all four groups 24 and 48 hours after LPS instillation, respectively.
RESULTS
The TNF-alpha and IL-6 concentrations were significantly lower in the EP+LPS group than in the LPS group (p<0.05). The changes in the concentration of these inflammatory cytokines were strongly correlated with that of NF-kappaB (p<0.01). The ALI scores were significantly lower in the EP+LPS and LPS+EP groups compared with the LPS group (p<0.05). In the EP+LPS group, the MPO activity was significantly lower than the LPS group (p=0.019).
CONCLUSION
EP, either administered before or after LPS instillation, has protective effects against the pathogenesis of LPS-induced ALI. EP has potential theurapeutic effects on LPS-induced ALI.

Keyword

Acute lung injury; Lipopolysaccharide; Ethyl pyruvate

MeSH Terms

Acute Lung Injury*
Animals
Bronchoalveolar Lavage Fluid
Cytokines
Humans
Interleukin-6
Lung
Male
Mice
NF-kappa B
Peroxidase
Pyruvic Acid*
Tumor Necrosis Factor-alpha
Cytokines
Interleukin-6
NF-kappa B
Peroxidase
Pyruvic Acid
Tumor Necrosis Factor-alpha

Figure

• 

  Figure 1 Study groups and protocol. The mice were divided into control, LPS, EP+LPS, and LPS+EP groups. In the control group, balanced salt solution was injected intraperitoneally 30 minutes before or 9 hours after intratracheal instillation of saline. In the LPS group, balanced salt solution was also injected intraperitoneally 30 minutes before or 9 hours after intratracheal instillation of LPS. 40mg/Kg of EP was injected 30 minutes before LPS instillation in the EP+LPS group and was injected 9 hours after LPS instillation in the LPS+EP group. The concentration of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF), and that of NF-κB in lung tissue were measured in the control, LPS and EP+LPS groups at 6 hours after intratracheal instillation of saline or LPS, and ALI score and myeloperoxidase (MPO) activity was measured in all four groups 24 and 48 hours after LPS instillation, respectively.

• 

  Figure 2 The concentration of tumor necrosis factor-α (TNF-α) (A) and interleukin-6 (IL-6) (B) in bronchoalveolar lavage fluid (BALF) was significantly decreased in EP+LPS group than LPS group (*p<0.05). ND: not detected

• 

  Figure 3 The concentration of nuclear factor-κB (NF-κB) in lung homogenate of the EP+LPS group was significantly lower than the LPS group and higher than the control group (*p<0.05). It was significantly correlated with tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) (r=Spearman's rho, **p<0.01).

• 

  Figure 4 Histopathologic examination shows high levels of inflammatory cellular infiltration, hemorrhage, and alveolar wall thickening in the LPS group. In the EP+LPS and LPS+EP group, the degree of acute lung injury was lower and only mild inflammatory cellular infiltration was observed compared with the control group.

• 

  Figure 5 Acute lung injury (ALI) scores were significantly different among four groups (p=0.000 by Kruskal-Wallis test). In the EP+LPS group, the score was significantly lower than the LPS group and higher than the control group (*p<0.05). And the score of the LPS+EP group was also significantly lower compared with the LPS group (**p=0.017) without significance between the control and the EP+LPS group (p>0.05).

• 

  Figure 6 The myeloperoxidase (MPO) activity in bronchoalveolar lavage fluid (BALF) was significantly lower in the EP+LPS group compared with the LPS group (*p=0.019) (A). However, in the LPS+EP group, the activity showed only decreasing trends without significant difference (†p=0.931) (B)

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