ABSTRACT
PURPOSE: The possible effects of ramelteon, a melatonin receptor agonist on bleomycin-induced lung fibrosis were analyzed via transforming growth factor ß1 (TGF-ß1), 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 âmL of 5 âmg/kg) was administered by intratracheal instillation to induce pulmonary fibrosis (PF). Starting 24 âh after bleomycin administration, a single dose of ramelteon was administered by oral gavage to the healthy groups, i.e. PF â+ âRM2 (pulmonary fibrosis model with bleomycin â+ âramelteon at 2 âmg/kg) and PF â+ âRM4 (pulmonary fibrosis model with bleomycin â+ âramelteon at 4 âmg/kg) at 2 and 4 âmg/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-ß1, HMGB1, NLRP3, and interleukin 1 beta (IL-1ß) mRNA expressions increased as a result of PF and subsequently decreased with both ramelteon doses (p â< â0.0001). 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.
