Attenuation of MMP-9 and fibronectin expression by Eugenol nanoemulsion in bleomycin-induced pulmonary fibrosis

Abstract

Pulmonary fibrosis (PF) is a chronic and progressive lung disease especially after severe acute coronavirus disease 2019 (COVID-19) infection, characterized by the formation of dense fibrous connective tissues. The present study is conducted to investigate the anti-fibrotic effects of eugenol oil (Eug) and eugenol nanoemulsion (Eug-NE) against pulmonary fibrosis induced by bleomycin (BLM) in rats. Lung fibrosis is induced by BLM in adult male rats. The animals were given Eug oil, Eug-NE, or dexamethasone (DXA) orally for 4 weeks, daily, starting one day after BLM. Lung injury, edema, and collagen deposition were determined. Some biochemical measurements, gene expression of apoptotic markers, immunohistochemistry, and histopathological examination of lung tissue are performed. The results revealed significant deterioration in lung tissues by BLM that is confirmed markedly by the pro-inflammatory, pro-oxidative, profibrotic, and pro-apoptotic conditions in lung tissues. However, treatment with Eug-NE potentially exhibited anti-fibrotic effects in lungs by downregulation of MMP-9, TGF-β and hence fibronectin expression. It also have the potential to cease the vicious cycle of epithelial injury caused by their anti-inflammatory and antiapoptotic effects. The effects of eugenol nanoemulsion were better than those of DXA. In conclusion the present study provides new insight into the use of natural oils in nano-emulsified formulations to treat pulmonary fibrosis which is one of the currently spread disorders as a result of severe COVID-19 infection.