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Abstract <p>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&#xa0;mg/kg) and DSF (1, 10, 100&#xa0;mg/kg) for 21 days. Lung tissues were analyzed histopathologically (H&amp;E, Mallory’s trichrome) for inflammation, alveolar septal thickening, vascular congestion, and fibrosis, while <i>Zeb1</i> gene expression was assessed by real-time PCR. PQ exposure led to severe lung injury, collagen deposition, and significant upregulation of <i>Zeb1</i> (<i>p</i> = 0.0022). DSF at 10&#xa0;mg/kg provided the most effective protection, significantly reducing histopathological damage and <i>Zeb1</i> expression (<i>p</i> &lt; 0.001). The 1&#xa0;mg/kg dose showed moderate efficacy, and the 100&#xa0;mg/kg dose had limited benefits, suggesting a dose-dependent toxicity. These findings indicate that DSF at 10&#xa0;mg/kg attenuates PQ-induced pulmonary fibrosis by reducing inflammation, collagen accumulation, and <i>Zeb1</i>-mediated profibrotic signaling, supporting DSF as a potential repurposed antifibrotic therapy for PQ-induced and possibly idiopathic pulmonary fibrosis.</p> Graphical abstract <p></p>

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Repurposing disulfiram: targeting Zeb1 to attenuate paraquat-induced pulmonary fibrosis in rats

  • 期刊论文

  • 发表日期：

    2025年9月18日

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  • Fatemeh Karimzadeh,
  • Abdolreza Daraei,
  • Ebrahim Zabihi-Neyshaburi,
  • Farideh Feizi,
  • Mohammad Ranaee,
  • Soraya Khafri,
  • Zohre Esmaeili,
  • Zahra Babazadeh

摘要

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.

Graphical abstract