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

Abstract

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. 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. 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. 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.