Alleviation of LPS-induced acute lung injury by propolis-based nanocomposites through the TLR4/NFKB and P2X7/AKT pathways: Randomized-controlled experimental study


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Üstündağ H., Kara A., Gökhan Taş N., Danişman Kalindemi̇rtaş F., Kurt N., Erbaş E., ...Daha Fazla

Toxicon, cilt.258, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 258
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1016/j.toxicon.2025.108330
  • Dergi Adı: Toxicon
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, Environment Index, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Anahtar Kelimeler: Apoptosis, Cytokines, Inflammation, Lung injury, Nanoparticles, Oxidative stress, Propolis, Sepsis
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Atatürk Üniversitesi Adresli: Evet

Özet

Sepsis-associated acute lung injury continues to pose a significant medical challenge with substantial morbidity and mortality rates. In this study, we investigated the therapeutic potential of propolis-based treatments and their nanocomposites in modulating inflammation and apoptosis using a lipopolysaccharide (LPS)-induced rat model of sepsis. Forty-two Sprague-Dawley rats were divided into seven groups (n = 6): control, LPS (5 mg/kg, i.p.), LPS + Propolis (100 mg/kg, i.p.), LPS + NanoPropolis (100 mg/kg, i.p.), LPS + silver nanoparticles propolis (AgNPsPro) (50 mg/kg), and a negative propolis group (100 mg/kg, i.p.). The rats were assessed for inflammatory, oxidative stress, and apoptotic markers through Western blot, histopathological analyses, and biochemical measurements. The LPS group exhibited significantly higher levels of pro-inflammatory cytokines (IL-1β, TNF-α) and the systemic infection marker presepsin (PRSN) in blood, as well as the oxidative stress marker malondialdehyde (MDA) in lung tissue. The treatment groups, particularly LPS + AgNPsPro, showed significant reductions in these markers, with decreased levels of MDA, IL-1β, TNF-α, NF-κB, and TLR4, and increased GSH content in lung tissue (p < 0.05). The anti-apoptotic protein BCL-2 was upregulated, while pro-apoptotic BAX expression was reduced, indicating enhanced cell survival. The P2X7 receptor, a key inflammation regulator, and the AKT signaling pathway, involved in cell survival, were positively modulated by the treatments. Histopathological findings corroborated these results, showing less lung tissue damage. In conclusion, propolis-based treatments, especially in combination with nanoparticles, demonstrate therapeutic potential in reducing inflammation, oxidative stress, and apoptosis in sepsis-induced lung injury.