Carvacrol Mitigates Bleomycin-Induced Experimental Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a serious progressive pulmonary disease of unknown etiology and high mortality. Carvacrol is a natural phenolic monoterpene with various pharmacological effects, especially antioxidant and anti-inflammatory effects. Hence, the present study aimed to investigate the effect of carvacrol on bleomycin (BLM) induced pulmonary fibrosis (PF) in Wistar-albino rats. Rats were administered a single dose of BLM (5mg/kg, intratracheal) or vehicle and treated with carvacrol (100 mg/kg, p.o. for 14 days following BLM administration). For calculating the lung index, the body and lungs were weighed. The Elisa method was used to assess hydroxyproline content, anti-inflammatory, and antioxidant effects. Fibrosis score, collagen deposition and inflammation were evaluated with Hematoxylin-Eosin (HxE) and Masson’s trichrome staining. Inducible nitric oxide synthase (iNOS), transforming growth factor-beta 1 (TGF-β1), and caspase 3 expressions were assessed immunohistochemically. BLM administration significantly diminished glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities and increased malondialdehyde (MDA) levels. BLM also increased tumor necrosis factor alpha (TNF-α) and collagen bundle accumulation. Carvacrol at 100 mg/kg significantly decreased collagen accumulation, MDA, TNF-α levels, iNOS, TGF-1, and caspase 3 expression, while increasing SOD and GPx activity. Histopathological examination supported the findings that carvacrol attenuated the degree of collagen deposition and inflammation. This study revealed that treatment with carvacrol (100 mg/kg) exhibits a potential healing effect on BLM-induced PF by reducing inflammatory and oxidative damages and histopathological alterations, with possible molecular targets being iNOS, TGF-β1 and caspase 3 signaling pathways.