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Aim <p>Levofloxacin (Levo), although a widely used powerful antibiotic, can cause serious toxicity in the liver via oxidative stress and apoptosis. This study aimed to investigate the effects of naringin (NRG), a natural flavonoid obtained from citrus fruits and distinguished by its strong antioxidant/anti-inflammatory properties, against Levo-induced liver damage.</p> Materials-methods <p>In the study, 35 <i>Wistar albino</i> rats were divided into Control, NRG, Levo, Levo+NRG50, and Levo+NRG100 groups and administered the respective treatments for 14 days. Toxicity and protective effects were assessed using liver function tests (ALT, AST, ALP), oxidative stress markers (MDA, SOD, CAT, GSH), and molecular analyses. Gene expression levels were determined using quantitative real-time PCR (qRT-PCR), while tissue damage and protein localization were assessed by histopathological examination (H&amp;E staining) and immunohistochemical analyses.</p> Results <p>NRG decreased (<i>p</i> &lt; 0.001) the markers of ALT, AST, MDA, inflammation (NF-κB, TNF-α, IL-1β), apoptosis (Caspase-3, Bax), ER stress (PERK, GRP-78, ATF-6) and autophagy (Beclin-1, LC3A, LC3B) increased by Levo, and also increased the levels of GSH, SOD, CAT, GPx, Nrf-2, HO-1 and Wnt-3a, Cyclin-D1, Dvl-2, demonstrating its hepatoprotective effect. Histopathological findings and immunohistochemical Caspase-3 staining also showed significant improvement with NRG.</p> Conclusion <p>These findings reveal the protective effect of Naringin against Levo-induced oxidative stress, inflammation, apoptosis, ER stress, autophagy, and tissue damage.</p> Graphical Abstract <p></p>

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Hepatoprotective Role of Naringin Against Levofloxacin Toxicity: Effect on Oxidative Damage, and Different Damage Pathways Gene Expression

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月3日

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  • Havva Nur Yılmaz Şebci,
  • Hüseyin Mutlu,
  • Hasan Şimşek,
  • Nurhan Akaras,
  • Özge Kandemir,
  • Fatih Mehmet Kandemir

摘要

Aim

Levofloxacin (Levo), although a widely used powerful antibiotic, can cause serious toxicity in the liver via oxidative stress and apoptosis. This study aimed to investigate the effects of naringin (NRG), a natural flavonoid obtained from citrus fruits and distinguished by its strong antioxidant/anti-inflammatory properties, against Levo-induced liver damage.

Materials-methods

In the study, 35 Wistar albino rats were divided into Control, NRG, Levo, Levo+NRG50, and Levo+NRG100 groups and administered the respective treatments for 14 days. Toxicity and protective effects were assessed using liver function tests (ALT, AST, ALP), oxidative stress markers (MDA, SOD, CAT, GSH), and molecular analyses. Gene expression levels were determined using quantitative real-time PCR (qRT-PCR), while tissue damage and protein localization were assessed by histopathological examination (H&E staining) and immunohistochemical analyses.

Results

NRG decreased (p < 0.001) the markers of ALT, AST, MDA, inflammation (NF-κB, TNF-α, IL-1β), apoptosis (Caspase-3, Bax), ER stress (PERK, GRP-78, ATF-6) and autophagy (Beclin-1, LC3A, LC3B) increased by Levo, and also increased the levels of GSH, SOD, CAT, GPx, Nrf-2, HO-1 and Wnt-3a, Cyclin-D1, Dvl-2, demonstrating its hepatoprotective effect. Histopathological findings and immunohistochemical Caspase-3 staining also showed significant improvement with NRG.

Conclusion

These findings reveal the protective effect of Naringin against Levo-induced oxidative stress, inflammation, apoptosis, ER stress, autophagy, and tissue damage.

Graphical Abstract