Experimental paperEffect of N-acetylcysteine (NAC) on acute lung injury and acute kidney injury in hemorrhagic shock☆,☆☆
Introduction
Ischemic and reperfusion injury that results from hemorrhagic shock (HS) induce the development of systemic inflammatory response syndrome and subsequent multiple organ failure including acute lung injury (ALI) and acute kidney injury (AKI). In patients with multiple organ failure, inflammatory cytokines and reactive oxygen species are mobilized into the systemic circulation and marginate to end organs, causing direct local cytotoxic cellular effects.1
N-acetylcysteine (NAC) is a reactive oxygen species (ROS) scavenger2 which elicits beneficial effects on inflammation process, such as suppression of cytokine expression/release, and inhibition of nuclear factor kappa B (NF-κB).3, 4, 5 NAC effects on ALI or AKI has been evaluated in various experimental conditions including endotoxemia,6, 7 fat embolism,8 cardiopulmonary bypass model,5 ischemic renal failure9 and hemorrhagic shock.10
NAC showed beneficial effect in most studies except in HS model.10 In that study, NAC was administrated by oral route for 3 days before the experiment. The plasma half-life of NAC is relatively short and no NAC is detectable 10–12 h after oral administration.11 Besides, recently it was reported that higher dose and continuous infusion of NAC are required to achieve acute antioxidant and anti-inflammatory effects.12, 13 Considering the dose and route of NAC in that study, the effect of NAC could not be maximized in previous study.10
In this context, we hypothesized that continuous administration of high dose NAC would reduce ALI and AKI in HS model.
Section snippets
Methods
This study was approved by the Institutional Animal Care and Use Committee of our hospital in accordance with policies and the animal protection laws.
Basic characteristics
All the animals examined in the study were alive during the experiments. Baseline characteristics including body weights, ABGA, and withdrawn blood amount was comparable between both groups (p > 0.05) (Table 1). MAP did not differ between the control and the NAC group at baseline, during shock state, reperfusion and observation period (p > 0.05) (Fig. 1).
Histological injury
ALI and AKI score were significantly lower in the NAC group (7.0 (5.0–8.25) vs. 8.5 (7.0–11.0), p = 0.04; 1.0 (1.0–2.0) vs. 2.0 (1.8–3.0), p = 0.04,
Discussion
This study demonstrated that continuous infusion of high dose NAC attenuated ALI and AKI in a rat model of HS. Oxidative stress, systemic inflammatory response, and histological injury were significantly lower in rats receiving NAC than in those receiving placebo. To the best of our knowledge, this is the first study evaluating the effect of continuous infusion of NAC on ALI and AKI in HS model.
There are several studies that antioxidants such as allopurinol, tempol, desferrioxamine, or
Conclusion
This study demonstrated that continuous infusion of NAC attenuated inflammatory response and acute lung and kidney injury after hemorrhagic shock in rats. Therefore, NAC could be considered as an adjunctive therapy in ALI and AKI after hemorrhagic shock.
Conflict of interest statement
We have no conflict of interest and any copyright constraints.
Source of support
This study was supported by grant no. 03-2012-022 from the SNUBH Research Fund.
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A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2012.05.017.
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This study was presented in 40th Society of Critical Care Medicine Conference and awarded as top 10 abstract.