Original articleGeneral thoracicEffect of N-Acetylcysteine on Acute Allograft Rejection After Rat Lung Transplantation
Section snippets
Animals
Specific pathogen-free, male Brown-Norway and Lewis rats (Harlan, Venray, the Netherlands), weighing 250 to 320 g, received adequate care in accordance with the Guide for the Use of Laboratory Animals (National Institutes of Health Publication 85-23, revised 1996; Bethesda, MD). The study protocol was approved by the local animal committee (License No. 214/2008).
Experimental Design
Orthotopic left lung Tx was performed from Brown-Norway donor rats to major histocompatibility complex–mismatched Lewis recipient
Oxygenation
On day 1, arterial blood oxygenation was not significantly different between transplant recipients (CON1, 21.6 ± 3.3 kPa; NAC1, 17.9 ± 4.0 kPa) and nontransplanted healthy rats (28.5 ± 1.1 kPa; p = 0.145 for CON1, p = 0.267 for NAC1). Arterial oxygenation in NAC5 (8.7 ± 2.7 kPa) was significantly lower than in nontransplanted animals (p = 0.024). In contrast, only 3 animals in CON5 tolerated clamping of the nontransplanted lung. The measured value (5.2 ± 0.6 kPa) is therefore not representative
Comment
We designed the present study to investigate a potential effect of the antioxidant NAC on acute rejection of lung allografts. We found that (1) NAC treatment has a significant influence on the GSH pool in the lung, such that GSH is significantly decreased on day 1 after Tx but can be increased to near physiologic levels by NAC administration; (2) NAC treatment significantly reduces NF-κB activation; and (3) this is reflected by significantly less macrophage and T-cell infiltration in the NAC
References (38)
- et al.
Primary graft failure following lung transplantation
Chest
(1998) - et al.
The Registry of the International Society for Heart and Lung Transplantation: twenty-seventh official adult lung and heart-lung transplant report—2010
J Heart Lung Transplant
(2010) - et al.
Systemic and pulmonary oxidative stress in idiopathic pulmonary fibrosis
Free Radic Biol Med
(1999) - et al.
Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches
Free Radic Biol Med
(2000) - et al.
Environmental toxicity, redox signaling and lung inflammation: the role of glutathione
Mol Aspects Med
(2009) - et al.
Glutathione downregulates the phosphorylation of I kappa B: autoloop regulation of the NF-kappa B-mediated expression of NF-kappa B subunits by TNF-alpha in mouse vascular endothelial cells
Biochem Biophys Res Commun
(1998) - et al.
Nacystelyn inhibits oxidant-mediated interleukin-8 expression and NF-kappaB nuclear binding in alveolar epithelial cells
Free Radic Biol Med
(2002) - et al.
N-Acetylcysteine attenuates lung ischemia-reperfusion injury after lung transplantation
Ann Thorac Surg
(2007) - et al.
Prevention of primary graft dysfunction in lung transplantation by N-acetylcysteine after prolonged cold ischemia
J Heart Lung Transplant
(2010) - et al.
Revision of the 1995 working formulation for the standardization of nomenclature in the diagnosis of lung rejection
J Heart Lung Transplant
(2007)