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Background <p>Amiodarone (AMD)-induced pulmonary fibrosis (PF) is a serious adverse effect driven by oxidative stress and inflammation. Naringenin [NAR], a citrus flavonoid, possesses potent antioxidant and anti-inflammatory properties. This study investigated the protective effects of NAR against AMD-induced PF in rats, focusing on the sirtuin 1; nuclear factor Kappa -B (SIRT1/NF-κB) pathway.</p> Methods <p>Thirty-two male Wistar rats were divided into four experimental groups (<i>n</i> = 8): control (CON), (NAR), (AMD), and AMD + NAR. In the AMD groups, PF was induced using AMD. NAR treatment was administered daily via oral gavage for five weeks.</p> Results <p>After 5 weeks, the AMD group exhibited significant alveolar damage and collagen deposition. Biochemically, AMD induced severe oxidative stress, characterized by increased malondialdehyde and nitric oxide (NO) levels. It also depleted antioxidant defences, including reduced glutathione (GSH) and superoxide dismutase (SOD). A robust inflammatory response was observed, with elevated levels of tumor necrosis factor -alpha (TNF-α), (NF-κB), and interleukin-6 (IL-6). The profibrotic cascade was activated through increased transforming growth factor beta 1(TGF-β1) and matrix metalloproteinase (MMP-2), alongside the upregulation of connective tissue growth factor (CTGF) and platelet derived growth factor (PDGF) mRNA. Apoptotic signalling was heightened by decreased B-cell lymphoma2 (Bcl-2) levels. Crucially, AMD downregulated SIRT1 and mitogen activated protein kinase (MAPK1/ERK2) mRNA expression. Conversely, NAR co-treatment significantly attenuated histopathological changes and reduced fibrosis scores. NAR effectively mitigated oxidative stress and restored antioxidant defenses. It also suppressed inflammatory and modulates anti-apoptotic signalling pathways. Notably, NAR decreased TGF-β1, MMP-2, CTGF, and PDGF, while restoring SIRT1 and MAPK1/ERK2 expression.</p> Conclusions <p>NAR provides significant protection against AMD-induced PF by reducing oxidative stress, inflammation, and modulating anti-apoptotic signalling pathways. These effects are likely mediated through the modulation of the SIRT1/NF-κB signalling pathway. This suggests NAR as a potential therapeutic candidate for drug-induced lung injury.</p>

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Naringenin attenuates amiodarone-induced pulmonary fibrosis in rats via modulation of the SIRT1/NF-κB signalling pathway

  • 期刊论文

  • 发表日期：

    2026年7月8日

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  • Heba M. Arakeep,
  • Wafaa Abdelaziz Emam,
  • Amena Rezk Mohammed,
  • Marwa H Sedira,
  • Marwa Mahmoud Awad,
  • Alshimaa Aboalsoud,
  • Rehab Ahmed,
  • Ahmed El-Shaer,
  • Azza Mostafa,
  • Mohammed Aboshanady,
  • Norhan Ahmed AbuoHashish

摘要

Background

Amiodarone (AMD)-induced pulmonary fibrosis (PF) is a serious adverse effect driven by oxidative stress and inflammation. Naringenin [NAR], a citrus flavonoid, possesses potent antioxidant and anti-inflammatory properties. This study investigated the protective effects of NAR against AMD-induced PF in rats, focusing on the sirtuin 1; nuclear factor Kappa -B (SIRT1/NF-κB) pathway.

Methods

Thirty-two male Wistar rats were divided into four experimental groups (n = 8): control (CON), (NAR), (AMD), and AMD + NAR. In the AMD groups, PF was induced using AMD. NAR treatment was administered daily via oral gavage for five weeks.

Results

After 5 weeks, the AMD group exhibited significant alveolar damage and collagen deposition. Biochemically, AMD induced severe oxidative stress, characterized by increased malondialdehyde and nitric oxide (NO) levels. It also depleted antioxidant defences, including reduced glutathione (GSH) and superoxide dismutase (SOD). A robust inflammatory response was observed, with elevated levels of tumor necrosis factor -alpha (TNF-α), (NF-κB), and interleukin-6 (IL-6). The profibrotic cascade was activated through increased transforming growth factor beta 1(TGF-β1) and matrix metalloproteinase (MMP-2), alongside the upregulation of connective tissue growth factor (CTGF) and platelet derived growth factor (PDGF) mRNA. Apoptotic signalling was heightened by decreased B-cell lymphoma2 (Bcl-2) levels. Crucially, AMD downregulated SIRT1 and mitogen activated protein kinase (MAPK1/ERK2) mRNA expression. Conversely, NAR co-treatment significantly attenuated histopathological changes and reduced fibrosis scores. NAR effectively mitigated oxidative stress and restored antioxidant defenses. It also suppressed inflammatory and modulates anti-apoptotic signalling pathways. Notably, NAR decreased TGF-β1, MMP-2, CTGF, and PDGF, while restoring SIRT1 and MAPK1/ERK2 expression.

Conclusions

NAR provides significant protection against AMD-induced PF by reducing oxidative stress, inflammation, and modulating anti-apoptotic signalling pathways. These effects are likely mediated through the modulation of the SIRT1/NF-κB signalling pathway. This suggests NAR as a potential therapeutic candidate for drug-induced lung injury.