@article{Xie:2026:10.1007/s00408-026-00875-1,
author = {Xie, M and Weng, J and Li, C and Liu, Q and Feng, Y and Zhang, H and Chang, Q and Chung, KF and Adcock, IM and Li, F and Fan, X},
doi = {10.1007/s00408-026-00875-1},
journal = {Lung},
title = {Mechanisms of Anti-Oxidants, N-Acetylcysteine and Elamipretide (SS-31), on Ozone-Induced Airway Hyperresponsiveness and Mucus Hypersecretion.},
url = {http://dx.doi.org/10.1007/s00408-026-00875-1},
volume = {204},
year = {2026}
}

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TY  - JOUR
AB  - BACKGROUND: Ozone (O) exposure induces acute airway injury characterized by airway hyperresponsiveness (AHR) and airway mucus hypersecretion (AMH). Oxidative stress and mitochondria-derived reactive oxygen species (mtROS) are key contributors. We investigated and compared the protective mechanisms of N-acetylcysteine (NAC) and the mitochondria-targeted antioxidant Elamipretide (SS-31) in O-induced airway inflammation, AHR and AMH. METHODS: Wild-type C57BL/6J mice received intraperitoneal NAC or SS-31 1 h before a single O exposure. AHR, bronchoalveolar lavage (BAL) inflammatory cells, mucus production and mucin expression, inflammatory mediators, oxidative stress indices, and PI3K/AKT and NLRP3/caspase-1/GSDMD pathway activation were assessed in vivo. BEAS-2B cells were pretreated with NAC, SS-31, or the PI3K/AKT inhibitor LY294002 before O exposure, and pathway activation was evaluate d in vitro. RESULTS: NAC and SS-31 comparably attenuated O-induced AHR, reduced BAL inflammatory cell influx, and decreased AMH and MUC5B expression. Both treatments improved redox balance by reducing ROS/mtROS, lowering malondialdehyde (MDA), increasing superoxide dismutase (SOD) activity, and improving GSH/GSSG. NAC and SS-31 also suppressed O-induced inflammatory gene expression and inhibited activation of PI3K/AKT and NLRP3/caspase-1/GSDMD signaling in mouse lungs and BEAS-2B cells. PI3K inhibition recapitulated these protective effects in vitro, supporting a mechanistic role for PI3K/AKT signaling during acute O exposure. CONCLUSIONS: NAC and SS-31 protect against acute O-induced AHR and AMH by alleviating oxidative stress and suppressing PI3K/AKT-driven inflammatory and pyroptotic pathways. Targeting oxidative stress, including mitochondrial ROS, may represent a viable strategy to mitigate airway damage caused by acute O exposure.
AU  - Xie,M
AU  - Weng,J
AU  - Li,C
AU  - Liu,Q
AU  - Feng,Y
AU  - Zhang,H
AU  - Chang,Q
AU  - Chung,KF
AU  - Adcock,IM
AU  - Li,F
AU  - Fan,X
DO  - 10.1007/s00408-026-00875-1
PY  - 2026///
TI  - Mechanisms of Anti-Oxidants, N-Acetylcysteine and Elamipretide (SS-31), on Ozone-Induced Airway Hyperresponsiveness and Mucus Hypersecretion.
T2  - Lung
UR  - http://dx.doi.org/10.1007/s00408-026-00875-1
UR  - https://www.ncbi.nlm.nih.gov/pubmed/41801306
VL  - 204
ER  - 

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