N-acetyl-l-cystine (NAC) protects against H9N2 swine influenza virus-induced acute lung injury

• DOI: 10.1016/j.intimp.2014.06.013
• Publication Date: 2014-06-24T04:16:05Z
• Authors: Rui-Hua Zhang; Chun-Hong Li; Cun-Lian Wang; Ming-Ju Xu; Tong Xu; Dong Wei; Bao-Jian Liu; Guo-Hua Wang; Shu-Fei Tian
• Keywords: Male; 0301 basic medicine; Mice, Inbred BALB C; Swine; Acute Lung Injury; Virus Replication; Article; Antioxidants; Acetylcysteine; 3. Good health; Toll-Like Receptor 4; Disease Models, Animal; Mice; 03 medical and health sciences; Lipid A; Orthomyxoviridae Infections; Influenza, Human; Influenza A Virus, H9N2 Subtype; Animals; Cytokines; Humans; Inflammation Mediators; Lung; Peroxidase

The antioxidant N-acetyl-l-cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on H9N2 swine influenza virus-induced acute lung injury (ALI) were investigated in mice. BALB/c mice were inoculated intranasally with 10(7) 50% tissue culture infective doses (TCID(50)) of A/swine/HeBei/012/2008/(H9N2) viruses with or without NAC treatments to induce ALI model. The result showed that pulmonary inflammation, pulmonary edema, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6, IL-1β and CXCL-10 in BALF were attenuated by NAC. Moreover, our data showed that NAC significantly inhibited the levels of TLR4 protein and TLR4 mRNA in the lungs. Pharmacological inhibitors of TLR4 (E5564) exerted similar effects like those determined for NAC in H9N2 swine influenza virus-infected mice. These results suggest that antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.