Hyperbaric oxygen therapy alleviates acute carbon monoxide poisoning-induced transition of cardiac fibroblast to myofibroblast and ameliorates cardiac fibrosis via the NRF2/ROS/TGFβ1/Smad pathway

  • Eur J Pharmacol. 2026 Jun 28:1028:178992. doi: 10.1016/j.ejphar.2026.178992.
Jianfei Wang  1 ,  Binhao Shi  2 ,  Yancheng Hao  3 ,  Lin Chai  3 ,  Mengru Chen  4 ,  Jing Zhang  5
Affiliations
  • 1. Anhui Province Key Laboratory of Occupational Health (Anhui No.2 Provincial People's Hospital), Hefei City, China; Department of Cardiology, Anhui No.2 Provincial People's Hospital, Hefei City, China; Graduate School of Bengbu Medical University, Bengbu City, China; Anhui University of Science and Technology, Huainan City, China. Electronic address: [email protected].
  • 2. Department of Cardiology, Anhui No.2 Provincial People's Hospital, Hefei City, China.
  • 3. Department of Cardiology, Anhui No.2 Provincial People's Hospital, Hefei City, China; Graduate School of Bengbu Medical University, Bengbu City, China.
  • 4. Department of Cardiology, Anhui No.2 Provincial People's Hospital, Hefei City, China; Anhui University of Science and Technology, Huainan City, China.
  • 5. Anhui Province Key Laboratory of Occupational Health (Anhui No.2 Provincial People's Hospital), Hefei City, China. Electronic address: [email protected].
PMID: 42162689 DOI: 10.1016/j.ejphar.2026.178992
Abstract

Background: Acute carbon monoxide poisoning (ACOP) is one of the leading causes of poisoning-related deaths worldwide, inducing severe complications such as myocardial fibrosis and cardiac dysfunction. Hyperbaric oxygen (HBO) therapy is an effective clinical treatment for carbon monoxide (CO) poisoning, but its underlying mechanisms require further investigation.

Methods: An ACOP mouse model was established and treated with HBO. Carboxyhemoglobin (COHb) levels were measured, and myocardial histopathological changes and Collagen deposition were determined via hematoxylin-eosin staining, Masson's trichrome staining, and immunohistochemical staining. An ACOP cell model was constructed in the human cardiac fibroblast line HCF. Cell proliferation and migration were tested in CCK-8 and Transwell assays. The DHE fluorescent probe was applied in the determination of intracellular Reactive Oxygen Species (ROS) levels. Alpha-Smooth Muscle Actin (α-SMA) expression was examined by immunofluorescence. Finally, qRT-PCR and Western blot were used to measure the expression of fibrosis markers and proteins related to the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2)/Transforming Growth Factor Beta 1 (TGF-β1)/Mothers Against Decapentaplegic Homolog (Smad) pathway.

Results: HBO therapy significantly reduced COHb levels, improved myocardial histopathological changes and Collagen deposition, repressed cell proliferation and migration, and alleviated oxidative stress. Mechanistically, HBO therapy activated the NRF2 signaling pathway, reduced ROS levels, and suppressed the TGF-β1/Smad signaling pathway, thus mitigating the transition of cardiac fibroblasts to myofibroblasts.

Conclusion: HBO therapy effectively represses ACOP-induced cardiac fibroblast-to-myofibroblast transition and ameliorates cardiac fibrosis by modulating the NRF2/ROS/TGF-β1/Smad signaling pathway.

Keywords
Acute carbon monoxide poisoning; Cardiac fibrosis; Hyperbaric oxygen therapy; NRF2; ROS/TGFβ1/smad.
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