Cannabidiol attenuates lung ischemia-reperfusion injury by modulating RIPK1/RIPK3-mediated necroptosis and HIF-Ια/ VEGF signaling

ÇAMAŞ H. E., SAVRAN M., YILDIRIM S., AKIN S. E., YAZKAN R., İLHAN İ., ...Daha Fazla

Iranian Journal of Basic Medical Sciences, cilt.29, sa.5, ss.766-773, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 29 Sayı: 5
  • Basım Tarihi: 2026
  • Doi Numarası: 10.22038/ijbms.2026.90024.19406
  • Dergi Adı: Iranian Journal of Basic Medical Sciences
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, Index Islamicus, Directory of Open Access Journals, Academic Search Ultimate (EBSCO), Middle East & Africa Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
  • Sayfa Sayıları: ss.766-773
  • Anahtar Kelimeler: Cannabidiol, Hypoxia-Inducible faetor 1 -alpha subunit, Ischemia, Lung injury, Necroptosis, Oxidative stress, Reperfusion, Vascular endothelial growth -faetor A
  • Süleyman Demirel Üniversitesi Adresli: Evet

Özet

Objeetive(s): Lung ischemia-reperfusion (IR) injury is a critical clinical condition charaeterized by oxidative stress, inflammation, and necroptosis, often leading to severe complications. Cannabidiol (CBD), a non-psychoaetive cannabinoid, has demonstrated anti-oxidant and anti-inflammatory properties, but its role in modulating lung IR injury remains incompletely understood. This study investigated the proteetive effeets of CBD on lung IR injury in rats, focusing on the RIPK1/RIPK3 necroptosis pathway and the HIF-1 α/VEGF/eNOS signaling axis. Materials and Methods: Forty male Wistar albino rats were randomized into four groups: control, IR, IR+CBD (5 mg/kg), and CBD-only. Histopathological, immunohistochemical (TNF-α, Caspase-3), biochemical (TOS, TAS, OSI), and gene expression (RIPK1, RIPK3, HIF-1 α, VEGF, eNOS) analyses were performed. The IR group exhibited significant oxidative stress, inflammation, and tissue damage, with elevated TNF-α, caspase-3, TOS, OSI, and necroptosis/apoptosis markers. Results: CBD treatment markedly attenuated these effeets, reducing oxidative stress (~TAS, -JzTOS/ OSI), suppressing inflammation (~TNIF-œ), and inhibiting both apoptotic (~Caspase-3) and necroptotic (~RIPK1/RIPK3) pathways. Additionally, CBD down-regulated HIF-1 α/VEGF/eNOS expression, suggesting modulation of hypoxia-responsive signaling. Conclusion: These findings demonstrate that CBD mitigates lung IR injury by targeting oxidative stress, inflammation, and cell death mechanisms, highlighting its potential as a therapeutic agent. Further preclinical and clinical studies are warranted to validate these results.