D-carvone attenuates LPS-induced acute lung injury via TLR4/NF-κB and Nrf2/HO-1 signaling pathways in rats


ULAŞ N., ÜSTÜNDAĞ H., ÖZKANLAR S., ERBAŞ E., Kara A., Özkanlar Y.

Naunyn-Schmiedeberg's Archives of Pharmacology, cilt.398, sa.9, ss.12215-12225, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 398 Sayı: 9
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1007/s00210-025-04024-y
  • Dergi Adı: Naunyn-Schmiedeberg's Archives of Pharmacology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, Veterinary Science Database
  • Sayfa Sayıları: ss.12215-12225
  • Anahtar Kelimeler: Apoptosis, Cytokines, D-carvone, Inflammation, Lung injury, Oxidative stress, Sepsis
  • Erzincan Binali Yıldırım Üniversitesi Adresli: Evet

Özet

Acute lung injury (ALI) is a severe respiratory disorder associated with high morbidity and mortality. Lipopolysaccharide (LPS) is widely used to induce ALI in animal models. D-carvone, a natural monoterpene, has been reported to possess anti-inflammatory and antioxidant properties. This study aimed to investigate the protective effects of D-carvone on LPS-induced ALI in rats. Thirty-six male rats were randomly divided into six groups (n = 6): control, D-carvone (10 mg/kg and 20 mg/kg p.o.), LPS (10 mg/kg E. coli lipopolysaccharide i.p.), and LPS + D-carvone (LPS with either 10 or 20 mg/kg D-carvone). D-carvone was administered orally once daily for 10 days. On day 10, sepsis was induced with LPS administration, and samples were collected after 6 h under deep anesthesia. LPS administration caused significant lung injury, as evidenced by increased histopathological scores, upregulation of pro-inflammatory markers (TLR4, IL-1β, TNF-α), and oxidative stress (increased MDA, decreased GSH and SOD). Treatment with D-carvone at both doses significantly attenuated these changes. D-carvone downregulated pro-inflammatory markers, upregulated anti-inflammatory (NRF2) and anti-apoptotic (Bcl-2) proteins, and reduced the levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-8) in lung tissues. In conclusion, D-carvone protects against LPS-induced ALI in rats, possibly through its anti-inflammatory and antioxidant properties. These findings suggest that D-carvone could be a potential therapeutic candidate for preventing and treating ALI.