Effect of N-acetylcysteine (NAC) on acute lung injury and acute kidney injury in hemorrhagic shock

Resuscitation. 2013 Jan;84(1):121-7. doi: 10.1016/j.resuscitation.2012.05.017. Epub 2012 Jun 1.

Abstract

Aim of the study: N-acetylcysteine (NAC) has been investigated to attenuate organ injury in various experimental and clinical studies. However, results in hemorrhagic shock (HS) were controversial. We determined the effects of continuous administration of NAC on acute lung injury (ALI) and acute kidney injury (AKI) in HS model.

Methods: Twenty male Sprague-Dawley rats were used. Pressure controlled HS model defined by mean arterial pressure (MAP) 40±2 mmHg for 90 min followed by resuscitation and observation was used. Rats (n=10 per group) were randomized into 2 groups with NAC or dextrose. Intravenous NAC was given continuously from 15 min after induction of HS to the end of observation period (2 h). We measured serum IL-6, nitrite/nitrate concentration. NF-κB p65 DNA binding activity, expressions of cytoplasmic phosphorylated IκB-α (p-IκB-α) and IκB-α, malondialdehyde (MDA) and histopathological injury scores in lung and kidney were also evaluated.

Results: MAP did not show any difference during the study period. NAC decreased histopathologic scores in both lung and kidney. Lung and kidney MDA levels were significantly lower in the NAC group compared to control group. Serum nitrite/nitrate and IL-6 were also significantly lower in the NAC group. The levels of lung cytoplasmic p-IκB-α expression was mitigated by NAC, and NF-κB p65 DNA binding activity was also significantly decreased in the NAC group.

Conclusions: Continuous infusion of NAC attenuated inflammatory response and acute lung and kidney injury after hemorrhagic shock in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / etiology
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / etiology
  • Animals
  • Arterial Pressure
  • Glucose / pharmacology
  • I-kappa B Proteins / metabolism
  • Interleukin-6 / blood
  • Male
  • Malondialdehyde / blood
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / blood
  • Nitrates / blood
  • Nitrites / blood
  • Oxidative Stress
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Shock, Hemorrhagic / complications
  • Shock, Hemorrhagic / drug therapy*

Substances

  • I-kappa B Proteins
  • Interleukin-6
  • NF-kappa B
  • Nfkbia protein, rat
  • Nitrates
  • Nitrites
  • NF-KappaB Inhibitor alpha
  • Malondialdehyde
  • Glucose
  • Acetylcysteine