N-acetylcysteine alleviates pulmonary inflammatory response during benzo[a]pyrene-evoked acute lung injury.

Abstract

Benzo[a]pyrene (BaP), a representative polycyclic aromatic hydrocarbon, exists widely in automobile emissions and polluted atmosphere. The current study aimed to describe pulmonary inflammation during BaP-induced acute lung injury (ALI). All mice except controls were intratracheally instilled with a single dose of BaP (90 μg per mouse). The alveolar structure was damaged, accompanied by numerous inflammatory cell infiltration around pulmonary interstitium and small airway. Airway wall area and mean linear intercept were reduced in BaP-exposed mouse lungs. By contrast, airway wall thickness and destructive index were elevated in BaP-exposed mouse lungs. Several inflammatory genes, such as Tnf-α, Il-1β, Il-6, Mip-2, Kc, and Mcp-1, were upregulated in mouse lungs. Phosphorylated IκBα was elevated in BaP-exposed mouse lungs. Nuclear translocation of NF-κB p65 and p50 was accordingly observed in BaP-exposed mouse lungs. Several molecules of the MAPK pathway, including JNK, ERK1/2, and p38, were activated in mouse lungs. Of interest, pretreatment with N-acetylcysteine (NAC), an antioxidant, alleviated BaP-induced ALI. Moreover, NAC attenuated BaP-induced inflammatory cell infiltration in mouse lungs and inflammatory gene upregulation in A549 cells. In addition, NAC attenuated BaP-induced NF-κB activation in A549 cells and mouse lungs. These results suggest that NAC alleviates pulmonary inflammatory response during BaP-evoked ALI.