Repurposing disulfiram: targeting Zeb1 to attenuate paraquat-induced pulmonary fibrosis in rats
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Abstract
Pulmonary fibrosis is a fatal condition marked by excessive extracellular matrix deposition and myofibroblast activation, with paraquat (PQ) being a potent inducer via oxidative stress and profibrotic signaling. This study evaluated the antifibrotic effects of disulfiram (DSF), an FDA-approved medication, in rats with PQ-induced pulmonary fibrosis. Forty male Wistar rats were divided into eight groups receiving PQ (40 mg/kg) and DSF (1, 10, 100 mg/kg) for 21 days. Lung tissues were analyzed histopathologically (H&E, Mallory's trichrome) for inflammation, alveolar septal thickening, vascular congestion, and fibrosis, while Zeb1 gene expression was assessed by real-time PCR. PQ exposure led to severe lung injury, collagen deposition, and significant upregulation of Zeb1 (p = 0.0022). DSF at 10 mg/kg provided the most effective protection, significantly reducing histopathological damage and Zeb1 expression (p < 0.001). The 1 mg/kg dose showed moderate efficacy, and the 100 mg/kg dose had limited benefits, suggesting a dose-dependent toxicity. These findings indicate that DSF at 10 mg/kg attenuates PQ-induced pulmonary fibrosis by reducing inflammation, collagen accumulation, and Zeb1-mediated profibrotic signaling, supporting DSF as a potential repurposed antifibrotic therapy for PQ-induced and possibly idiopathic pulmonary fibrosis.
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DIS attenuates paraquat-induced pulmonary fibrosis by suppressing inflammation, collagen accumulation, and zinc finger E-box binding homeobox 1-mediated profibrotic signaling.
“The drug attenuates paraquat-induced pulmonary fibrosis by suppressing inflammation, collagen accumulation, and zinc finger E-box binding homeobox 1 (Zeb1)-mediated profibrotic signaling, positioning it as a promising repurposed therapy for idiopathic pulmonary fibrosis.122”
From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [122]
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Benkő, B.-M., De Brito Parreirinha, N. S., Sebe, I., & Zelkó, R. (2026) · iScience · doi:10.1016/j.isci.2026.115441 · Cited by 2 · see citing works
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- Authors
- Karimzadeh, F., Daraei, A., Zabihi-Neyshaburi, E., Feizi, F., Ranaee, M., Khafri, S., Esmaeili, Z., & Babazadeh, Z.
- Affiliations
- Babol University of Medical Sciences (IR)
- Corresponding author
- Babazadeh, Zahra
- ORCID
- Venue
- Journal of Molecular Histology
- Published
- 2025-09-18
- Volume
- 56
- Issue
- 5
- Pages
- 318-318
- ISSN
- 1567-2379 (ISSN-L)
- 1567-2387
- OpenAlex
- W4414325786
- Cited by
- 3
- References
- 49
- Citations by year
- 2026: 3
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Journal of Molecular Histology (publishedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- The Vice-Chancellery for Research and Technology of Babol University of Medical Sciences. (IR.MUBABOL.HRI.REC.1398.247)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Surgery › Paraquat toxicity studies and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Keywords
- disulfiram, drug repurposing, pulmonary fibrosis, paraquat, ZEB1, antifibrotic therapy, idiopathic pulmonary fibrosis, oxidative stress, collagen deposition, lung inflammation, myofibroblast activation, extracellular matrix deposition
- MeSH terms
- Zinc Finger E-box-Binding Homeobox 1, Animals, Disease Models, Animal, Disulfiram, Lung, Male, Paraquat, Pulmonary Fibrosis, Rats, Wistar, Rats, Drug Repositioning
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