Header

UZH-Logo

Maintenance Infos

Effect of N-acetylcysteine on acute allograft rejection after rat lung transplantation


Erne, Barbara V; Jungraithmayr, Wolfgang; Buschmann, Johanna; Arni, Stephan; Weder, Walter; Inci, Ilhan (2013). Effect of N-acetylcysteine on acute allograft rejection after rat lung transplantation. Annals of Thoracic Surgery, 95(3):1021-1027.

Abstract

BACKGROUND: N-Acetylcysteine (NAC) attenuates ischemia-reperfusion injury after lung transplantation in animal models. The purpose of this study is to evaluate a protective effect of NAC against acute lung rejection.
METHODS: Rat single-lung transplantation was performed in four groups (n = 7 per group). In NAC groups, donors and recipients received NAC 150 mg/kg per day intraperitoneally before transplantation and recipients thereafter until euthanasia. Control groups (CON) received 0.5 mL of 0.9% saline solution intraperitoneally instead of NAC. Animals were euthanized on day 1 (CON1, NAC1) or day 5 (CON5, NAC5) after transplantation. Lung tissue was assessed by histology, immunohistochemistry for CD68+/CD163+ macrophages and CD3+ T cells, immunofluorescence for interleukin 4 and interleukin 12, concentration of reduced glutathione, and activated nuclear factor-kappa B.
RESULTS: CD68+ macrophages in CON5 accumulated significantly compared with NAC5 grafts (p < 0.001). No significant difference was observed for CD163+ macrophages on day 5. T cells were significantly more frequent in NAC1 (p < 0.001), but significantly less in NAC5 (p < 0.001) compared with control groups, respectively. Interleukin 4 and interleukin 12 expression did not differ between groups. Treatment with NAC significantly influenced glutathione levels (p = 0.019) and reduced nuclear factor-kappa B activation (p = 0.034) in transplanted lungs.
CONCLUSIONS: N-Acetylcysteine has the potential to attenuate acute pulmonary rejection by reduction of macrophage and T-cell infiltration, which is intimately linked to a reduced action of the nuclear factor-kappa B proinflammatory signaling pathway. In view of these observations, NAC should be considered a promising substance that could play a role in strategies for the prevention of acute rejection.

Abstract

BACKGROUND: N-Acetylcysteine (NAC) attenuates ischemia-reperfusion injury after lung transplantation in animal models. The purpose of this study is to evaluate a protective effect of NAC against acute lung rejection.
METHODS: Rat single-lung transplantation was performed in four groups (n = 7 per group). In NAC groups, donors and recipients received NAC 150 mg/kg per day intraperitoneally before transplantation and recipients thereafter until euthanasia. Control groups (CON) received 0.5 mL of 0.9% saline solution intraperitoneally instead of NAC. Animals were euthanized on day 1 (CON1, NAC1) or day 5 (CON5, NAC5) after transplantation. Lung tissue was assessed by histology, immunohistochemistry for CD68+/CD163+ macrophages and CD3+ T cells, immunofluorescence for interleukin 4 and interleukin 12, concentration of reduced glutathione, and activated nuclear factor-kappa B.
RESULTS: CD68+ macrophages in CON5 accumulated significantly compared with NAC5 grafts (p < 0.001). No significant difference was observed for CD163+ macrophages on day 5. T cells were significantly more frequent in NAC1 (p < 0.001), but significantly less in NAC5 (p < 0.001) compared with control groups, respectively. Interleukin 4 and interleukin 12 expression did not differ between groups. Treatment with NAC significantly influenced glutathione levels (p = 0.019) and reduced nuclear factor-kappa B activation (p = 0.034) in transplanted lungs.
CONCLUSIONS: N-Acetylcysteine has the potential to attenuate acute pulmonary rejection by reduction of macrophage and T-cell infiltration, which is intimately linked to a reduced action of the nuclear factor-kappa B proinflammatory signaling pathway. In view of these observations, NAC should be considered a promising substance that could play a role in strategies for the prevention of acute rejection.

Statistics

Citations

9 citations in Web of Science®
9 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
04 Faculty of Medicine > University Hospital Zurich > Clinic for Thoracic Surgery
04 Faculty of Medicine > University Hospital Zurich > Clinic for Reconstructive Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:22 Jan 2014 13:11
Last Modified:05 Apr 2016 16:43
Publisher:Elsevier
ISSN:0003-4975
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.athoracsur.2012.11.008
PubMed ID:23313471

Download

Full text not available from this repository.
View at publisher