Chrysin mitigates bleomycin-induced pulmonary fibrosis in rats through regulating inflammation, oxidative stress, and hypoxia

摘要

Pulmonary fibrosis is a chronic condition characterized by fibroblast proliferation, and the infiltration of inflammatory cells that can initiate local tissue hypoxia. In this study the effect of chrysin (50 mg/kg/orally) in a model of bleomycin (BLM)-induced pulmonary fibrosis was studied. Chrysin managed to decrease mortality rate associated with BLM instillation and it managed to improve lung architecture and lung fibrosis by decreasing hydroxyproline content and transforming growth factor-beta 1 (TGF-beta 1) protein expression. Chrysin showed anti-inflammatory effect displayed by the decrease in inflammatory cells infiltrates, the decline in permeability of the alveolar/capillary barrier and the reduction in lactate dehydrogenase (LDH) activity. Chrysin demonstrated potent antioxidant effect by decreasing lipid peroxidation, increasing antioxidant defense mechanisms by increasing superoxide dismutase (SOD) activity and reduced glutathione (GSH) content. Additionally, the effect of chrysin on nitric oxide (NOx) content was assessed, where chrysin decreased NOx, increased the protein expression of endothelial nitric oxide synthase (eNOS), and decreased inducible nitric oxide synthase (iNOS) protein expression. Chrysin also succeeded in decreasing thioredoxin-interacting protein (TXNIP), the negative regulator of thioredoxin system, showing potent antioxidant effect. Finally, both tissue and bronchoalveolar lavage fluid contents of hypoxia inducible factor one alpha (HIF1 alpha) were decreased by chrysin indicating that chrysin decreased local tissue hypoxia. In conclusion, this study exposed a possible proof that chrysin could mitigate pulmonary fibrosis induced by BLM through its anti-inflammatory, antioxidant, antifibrotic effects and its effect in alleviating hypoxia.y