Carvacrol Mitigates Bleomycin Induced Experimental Pulmonary Fibrosis

Abstract

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 antiinflammatory 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, antiinflammatory, 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 (TGFβ1), 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 (TNFα) 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.