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Disulfiram ameliorates bleomycin induced pulmonary inflammation and fibrosis in rats.
Hamidi, Negar; Feizi, Farideh; Azadmehr, Abbas; Zabihi, Ebrahim; Khafri, Soraya; Zarei-Behjani, Zeinab; Babazadeh, Zahra.
Afiliación
  • Hamidi N; Cellular and Molecular Biology Research Center, Institute of Health, Babol University of Medical Sciences, Babol, Iran.
  • Feizi F; Department of Anatomical Science, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
  • Azadmehr A; Cellular and Molecular Biology Research Center, Institute of Health, Babol University of Medical Sciences, Babol, Iran.
  • Zabihi E; Department of Anatomical Science, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
  • Khafri S; Cellular and Molecular Biology Research Center, Institute of Health, Babol University of Medical Sciences, Babol, Iran.
  • Zarei-Behjani Z; Department of Immunology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
  • Babazadeh Z; Cellular and Molecular Biology Research Center, Institute of Health, Babol University of Medical Sciences, Babol, Iran.
Biotech Histochem ; 98(8): 584-592, 2023 Nov.
Article en En | MEDLINE | ID: mdl-37779489
Bleomycin (BL) is a widely used anticancer drug that can cause pulmonary fibrosis due to increased fibroblast proliferation and increased secretion of extracellular matrix. RASSF1A is a tumor suppressor gene that is down-regulated by DNA methylation during fibrosis. Disulfiram (DSF), a noncytosine DNA methyltransferase inhibitor, can revert epigenetic biomarkers and re-express silenced genes. We investigated anti-inflammatory and anti-fibrotic effects of DSF on regulation of epigenetic molecules and histopathology in a rat model of BL induced pulmonary fibrosis. We used six groups of rats: sesame oil (SO) control (Co) group, BL group, BL + SO group and three BL + DSF groups administered 1 mg/kg DSF (BL + DSF), 10 mg/kg DSF (BL + DSF10) or 100 mg/kg DSF (BL + DSF100), respectively. BL was administered intratracheally to induce pulmonary fibrosis. DSF and SO were injected intraperitoneally (i.p.) 2 days before BL administration; these injections were continued for 3 weeks. At the end of the study, lung tissues were removed for molecular and histopathologic studies. Administration of 10 or 100 mg/kg DSF after BL induced pulmonary inflammation and fibrosis, and up-regulated RASSF1A and down-regulated TNF-α and IL-1 ß compared to the BL and BL + SO groups. A RASSF1A unmethylated band was observed using the methylation-specific PCR technique in rats that had been administered 10 and 100 mg/kg DSF, which indicated partial DNA demethylation. Histopathologic evaluation revealed that fibrosis and all inflammatory scores were decreased significantly in the BL + DSF10 and BL + DSF100 groups compared to the BL group. Our findings indicate that DSF modified DNA methylation by up-regulating RASSF1A, which reduced inflammation and fibrosis in BL induced pulmonary inflammation and fibrosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neumonía / Fibrosis Pulmonar Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biotech Histochem Asunto de la revista: HISTOCITOQUIMICA Año: 2023 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neumonía / Fibrosis Pulmonar Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biotech Histochem Asunto de la revista: HISTOCITOQUIMICA Año: 2023 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Reino Unido