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

Hilal Üstündağ, Adem Kara, Necip Gökhan Taş, Ferdane Danişman Kalindemi Rtaş, Nezahat Kurt, Elif Erbaş, Mehmet Tahir Huyut, Mustafa Gül, İshak Afşin Kari Per
Author Information
  1. Hilal Üstündağ: Department of Physiology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan, 2400, Türkiye. Electronic address: hilal.ustundag@erzincan.edu.tr.
  2. Adem Kara: Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, Türkiye.
  3. Necip Gökhan Taş: Erzincan Binali Yıldırım University Experimental Animals Application and Research Centre, Erzincan, Türkiye.
  4. Ferdane Danişman Kalindemi Rtaş: Department of Physiology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan, 2400, Türkiye.
  5. Nezahat Kurt: Department of Biochemistry, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan, Türkiye. Electronic address: nezahat.kurt@erzincan.edu.tr.
  6. Elif Erbaş: Department of Veterinary Histology and Embryology, Faculty of Veterinary Medicine, Erzurum, Türkiye.
  7. Mehmet Tahir Huyut: Department of Biostatistic, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan, 2400, Türkiye.
  8. Mustafa Gül: Department of Physiology, Faculty of Medicine, Ataturk University, Erzurum, 25240, Türkiye.
  9. İshak Afşin Kari Per: Department of Science Education, Faculty of Education, Erciyes University, Kayseri, Türkiye.

Abstract

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.

Keywords

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