Tuberc Respir Dis.  2012 Jul;73(1):22-31. 10.4046/trd.2012.73.1.22.

The Effect of Post-Treatment N-Acetylcysteine in LPS-Induced Acute Lung Injury of Rats

• Choi JS
• Lee HS
• Seo KH
• Na JO
• Kim YH
• Uh ST
• Park CS
• Oh MH
• Lee SH
• Kim YT

• KMID: 2050671
• DOI: http://doi.org/10.4046/trd.2012.73.1.22

Abstract

BACKGROUND
Oxidation plays an important role in acute lung injury. This study was conducted in order to elucidate the effect of repetitive post-treatment of N-acetylcysteine (NAC) in lipopolysaccaride (LPS)-induced acute lung injury (ALI) of rats.
METHODS
Six-week-old male Sprague-Dawley rats were divided into 4 groups. LPS (Escherichia coli 5 mg/kg) was administered intravenously via the tail vein. NAC (20 mg/kg) was injected intraperitoneally 3, 6, and 12 hours after LPS injection. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the ALI at 24 hours after LPS injection. The concentration of tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) were measured in BALF. Nuclear factor kappaB (NF-kappaB), lipid peroxidation (LPO), and myeloperoxidase (MPO) were measured using lung tissues. Micro-computed tomography (micro-CT) images were examined in each group at 72 hours apart from the main experiments in order to observe the delayed effects of NAC.
RESULTS
TNF-alpha and IL-1beta concentration in BALF were not different between LPS and NAC treatment groups. The concentration of LPO in NAC treatment group was significantly lower than that of LPS group (5.5+/-2.8 nmol/mL vs. 16.5+/-1.6 nmol/mL) (p=0.001). The activity of MPO in NAC treatment group was significantly lower than that of LPS group (6.4+/-1.8 unit/g vs. 11.2+/-6.3 unit/g, tissue) (p<0.048). The concentration of NF-kappaB in NAC treatment group was significantly lower than that of LPS group (0.3+/-0.1 ng/microL vs. 0.4+/-0.2 ng/microL) (p=0.0001). Micro-CT showed less extent of lung injury in NAC treatment than LPS group.
CONCLUSION
After induction of ALI with lipopolysaccharide, the therapeutic administration of NAC partially attenuated the extent of ALI through the inhibition of NF-kappaB activation.

Keyword

Acetylcysteine; Acute Lung Injury; Antioxidants

MeSH Terms

Acetylcysteine
Acute Lung Injury
Animals
Antioxidants
Humans
Interleukin-1beta
Lipid Peroxidation
Lung
Lung Injury
Male
NF-kappa B
Peroxidase
Rats
Rats, Sprague-Dawley
Therapeutic Irrigation
Tumor Necrosis Factor-alpha
Veins
Acetylcysteine
Antioxidants
Interleukin-1beta
NF-kappa B
Peroxidase
Tumor Necrosis Factor-alpha

Figure

• 

  Figure 1 The effects of N-acetylcysteine (NAC) of nuclear factor κB (NF-κB) and lipid peroxidation in lipopolysaccharide (LPS) induced acute lung injury. (A) Lipid peroxidation concentrations in lung tissue. In NAC treatment (LPS+NAC) group, lipid peroxidation concentration significantly decreased than that in LPS group. (B) NF-κB concentrations in lung tissue. NF-κB concentration in NAC treatment group significantly decreased more than that in LPS group. Box table: median (25~75%); except out-layer data.

• 

  Figure 2 Micro-computed tomography (micro-CT) of rat model. The N-acetylcysteine (NAC) group (A, right lung; B, left lung) shows normal lung parenchyma in micro-CT. The lipopolysaccharide (LPS) group (C) and NAC treatment group (NAC+LPS group) (D) show ground glass opacity pattern in Rt. lower lobe, but in NAC treatment (D), the ground glass opacity decreased more than that in LPS group (C).

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