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Abstract Title:

Thymoquinone treatment modulates the Nrf2/HO-1 signaling pathway and abrogates the inflammatory response in an animal model of lung fibrosis.

Abstract Source:

Exp Lung Res. 2020 Feb 13:1-11. Epub 2020 Feb 13. PMID: 32053036

Abstract Author(s):

Ajaz Ahmad, Khalid M Alkharfy, Basit Latief Jan, Abdul Ahad, Mushtaq Ahmad Ansari, Fahad I Al-Jenoobi, Mohammad Raish

Article Affiliation:

Ajaz Ahmad

Abstract:

The present study investigates the therapeutic potential of thymoquinone (TQ) in bleomycin-induced lung fibrosis (BMILF) and elucidates the target-signaling pathway for its effect. Lung fibrosis was induced in rats by a single intra-tracheal instillation of bleomycin (BM) (6.5 U/kg) followed by thymoquinone treatment (10 and 20 mg/kg p.o.) for 28 days. Control rats received saline instead of TQ. Changes in body weight, inflammatory cells count, cytokines levels, and biochemical parameters of the broncho-alveolar lavage fluid (BALF) were recorded. In addition, a histopathology examination and western blotting were performed on lung tissues. BM administration resulted in a significant weight loss, which was ameliorated by TQ treatment. BMILF was associated with a reduction in the antioxidant mechanisms and increased lipid peroxidation. Furthermore, elevated levels of inflammatory cytokines, MMP-7 expression, apoptotic markers (caspase 3, Bax, and Bcl-2), and fibrotic changes including TGF-β and hydroxyproline levels in lung tissues were evident. These abnormalities were diminished with TQ treatment. Likewise, altered total and differential cell count inBALF was significantly improved in rats treated with TQ. TQ also produced a dose-dependent reduction in the expressions of Nrf2, Ho-1 and TGF-β. These results propose that the Nrf2/Ho-1 signaling pathway is a principal target for TQ protective effect against BMILF in rats. Furthermore, TQ decreasesinflammatory oxidative stress possibly through the modulation of nuclear factor Kappa-B (NF-κB) and thereby minimization of collagen deposition in the lung. Therefore, TQ can be developed as a potential therapeutic modularity in BMILF for human use.

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