N-acetylcysteine administration confers lung protection in different phases of lung ischaemia-reperfusion injury.

Abstract

OBJECTIVES:

To verify the effects of N-acetylcysteine (NAC) administered before and after ischaemia in an animal model of lung ischaemia-reperfusion (IR) injury.

METHODS:

Twenty-four Wistar rats were subjected to an experimental model of selective left pulmonary hilar clamping for 45 min followed by 2 h of reperfusion. The animals were divided into four groups: control group (SHAM), ischaemia-reperfusion, N-acetylcysteine-preischaemia (NAC-Pre) and NAC-postischaemia (NAC-Post). We recorded the haemodynamic parameters, blood gas analysis and histology. We measured the thiobarbituric acid reactive substances concentration; the expression of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS), nitrotyrosine, cleaved caspase 3, nuclear factor κB (NF-κB), NF-kappa-B inhibitor alpha (IκB-α), tumour necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β); myeloperoxidase activity (MPO).

RESULTS:

No significant differences were observed in the haemodynamic parameters, blood gas analysis and SOD activity among the groups. Lipid peroxidation was significantly higher in the IR and NAC-Pre groups (P < 0.01). The expression of nitrotyrosine, cleaved caspase 3, NF-κB, IκB-α, TNF-α and IL-1β were significantly higher in the IR group when compared with the SHAM and NAC groups (P < 0.01). The NAC-Pre group showed a significantly higher expression of these proteins when compared with the SHAM and NAC-Post groups (P < 0.05). After reperfusion, the expression of iNOS increased almost uniformly in all groups when compared with the SHAM group (P < 0.01). The histological analysis showed fewer inflammatory cells in the NAC groups.

CONCLUSIONS:

The intravenous administration of NAC demonstrated protective properties against lung IR injury. The use of NAC immediately after reperfusion potentiates its protective effects.

• Authors: Luiz Felipe Forgiarini, Luiz Alberto Forgiarini Jr, Darlan Pase da Rosa, Mariel Barbachan E Silva, Rodrigo Mariano, Artur de Oliveira Paludo, Cristiano Feijó Andrade
• Journal: Interactive cardiovascular and thoracic surgery (Interact Cardiovasc Thorac Surg) Vol. 19 Issue 6 Pg. 894-9 (Dec 2014) ISSN: 1569-9285 [Electronic] England
• PMID: 25156898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• IL1B protein, rat
• Inflammation Mediators
• Interleukin-1beta
• NF-kappa B
• Tumor Necrosis Factor-alpha
• 3-nitrotyrosine
• Tyrosine
• Peroxidase
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Superoxide Dismutase
• I-kappa B Kinase
• Casp3 protein, rat
• Caspase 3
• Acetylcysteine

Topics

• Acetylcysteine (administration & dosage)
• Administration, Intravenous
• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Antioxidants (administration & dosage)
• Caspase 3 (metabolism)
• Cytoprotection
• Disease Models, Animal
• Hemodynamics (drug effects)
• I-kappa B Kinase (metabolism)
• Inflammation Mediators (metabolism)
• Interleukin-1beta (metabolism)
• Lipid Peroxidation (drug effects)
• Lung (blood supply, drug effects, metabolism, pathology)
• Lung Injury (metabolism, pathology, physiopathology, prevention & control)
• NF-kappa B (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Oxidative Stress (drug effects)
• Peroxidase (metabolism)
• Rats, Wistar
• Reperfusion Injury (metabolism, pathology, physiopathology, prevention & control)
• Superoxide Dismutase (metabolism)
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)
• Tyrosine (analogs & derivatives, metabolism)