N-acetylcysteine attenuates cardiopulmonary bypass-induced lung injury in dogs

Background: Cardiopulmonary bypass (CPB) is usually associated with inflammatory response that leads to various degrees of organ dysfunction in multiple systems, including lung injury. Our previous study showed that transforming growth factor beta1 (TGF beta 1) was involved in CPB-induced lung injury. N-acetylcysteine (NAC) is an antioxidant and is able to prevent CPB-induced pneumocyte apoptosis through scavenging radical. Therefore, we investigated whether NAC may attenuate CPB-induced lung injury by inhibiting TGF beta 1 expression. Methods: Fifty-four 18 to 24-month-old mongrel dogs (15-16 kg) were randomly divided into control group, CPB group and NAC group (n = 18). Six dogs in each group were killed prior to, as well as 30 and 60 minutes after the operation (T0, T1 and T2). Lung injury was evaluated by hematoxylin and eosin (H&E) staining. Respiratory index (RI), oxygenation index (OI), malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the lung were determined at each time point. TGF beta 1 expression was determined using real time RT-PCR and immunohistochemistry. Results: A serious lung injury was observed after CPB in dogs. RI and MDA content were increased significantly after CPB, whereas OI and SOD activity were decreased. H&E staining showed that NAC treatment obviously attenuated CPB-induced lung injury. NAC treatment upregulated OI and SOD activity and downregulated RI and MDA content in the lung tissues of dogs after CPB. Treatment with NAC significantly suppressed the TGF beta 1 expression in the lung tissues at both mRNA and protein levels. Conclusion: Our results suggest that NAC is a potent agent against CPB-induced acute lung injury through inhibiting TGF beta 1 expression.