N-acetylcysteine attenuates benzo[a]pyrene-exacerbated asthma lung injury by inhibiting mucous hypersecretion and apoptosis via the ROS/CREB/ERK pathway

OBJECTIVE: To investigate the protective effect of N-acetylcysteine (NAC) against benzo[a]pyrene (BaP)-aggravated lung injury in asthma and to elucidate whether it is mediated through the ROS/CREB/ERK signaling pathway. METHODS: gavage. Airway inflammation and mucus secretion were assessed by H&E and PAS staining. Serum IgE levels were measured by ELISA. SOD activity and MDA content were detected using commercial kits. ROS levels in lung tissue were observed by fluorescence staining. The mRNA expression of mucin genes (MUC5AC, MUC5B, MUC16, etc.) was detected by qPCR. The protein expression of apoptosis-related markers (Bax, Bcl-2) and signaling pathway components (p-ERK1/2, p-CREB) was measured by Western Blot. RESULTS: Compared with the Model group, NAC intervention significantly alleviated airway inflammatory cell infiltration, mucus hypersecretion, and epithelial damage, and reduced serum IgE levels. Meanwhile, NAC effectively decreased ROS and MDA levels, increased SOD activity in lung tissue, reversed the BaP-induced upregulation of MUC5AC, MUC5B, and MUC16 genes, and modulated the Bax/Bcl-2 ratio to inhibit apoptosis. Mechanistically, NAC significantly inhibited BaP-induced phosphorylation of ERK1/2 and CREB. CONCLUSION: NAC can mitigate BaP-induced airway mucus hypersecretion and apoptosis, thereby alleviating asthma lung injury, by scavenging ROS and inhibiting the overactivation of the ROS/CREB/ERK signaling pathway. This study provides experimental evidence supporting NAC as a potential therapeutic strategy for preventing and treating air pollution-associated asthma.