The melatonin agonist ramelteon attenuates bleomycin-induced lung fibrosis by suppressing the NLRP3/TGF-Β1/HMGB1 signaling pathway
Advances in Medical Sciences, cilt.68, sa.2, ss.322-331, 2023 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 68 Sayı: 2
- Basım Tarihi: 2023
- Doi Numarası: 10.1016/j.advms.2023.09.004
- Dergi Adı: Advances in Medical Sciences
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, EMBASE, Food Science & Technology Abstracts, MEDLINE
- Sayfa Sayıları: ss.322-331
- Anahtar Kelimeler: Fibrosis, Melatonin, NLRP3, Ramelteon, TGF-β1
- Sivas Cumhuriyet Üniversitesi Adresli: Evet
Özet
Purpose: The possible effects of ramelteon, a melatonin receptor agonist on bleomycin-induced lung fibrosis were analyzed via transforming growth factor β1 (TGF-β1), the high mobility group box 1 (HMGB1) and Nod-like receptor pyrin domain-containing 3 (NLRP3) which are related to the fibrosis process. Materials and methods: Bleomycin (0.1 mL of 5 mg/kg) was administered by intratracheal instillation to induce pulmonary fibrosis (PF). Starting 24 h after bleomycin administration, a single dose of ramelteon was administered by oral gavage to the healthy groups, i.e. PF + RM2 (pulmonary fibrosis model with bleomycin + ramelteon at 2 mg/kg) and PF + RM4 (pulmonary fibrosis model with bleomycin + ramelteon at 4 mg/kg) at 2 and 4 mg/kg doses, respectively. Real-time polymerase chain reaction (real-time PCR) analyses, histopathological, and immunohistochemical staining were performed on lung tissues. Lung tomography images of the rats were also examined. Results: The levels of TGF-β1, HMGB1, NLRP3, and interleukin 1 beta (IL-1β) mRNA expressions increased as a result of PF and subsequently decreased with both ramelteon doses (p < 0.0001). Both doses of ramelteon partially ameliorated the reduction in the peribronchovascular thickening, ground-glass appearances, and reticulations, and the loss of lung volume. Conclusions: The severity of fibrosis decreased with ramelteon application. These effects of ramelteon may be associated with NLRP3 inflammation cascade.