chrysin and Pulmonary-Fibrosis

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-β1 (TGF-β1) 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 (HIF1α) 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.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Bleomycin; Cell Cycle Proteins; Cell Hypoxia; Disease Models, Animal; Flavonoids; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation Mediators; Lipid Peroxidation; Lung; Male; Nitric Oxide; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Oxidative Stress; Pneumonia; Pulmonary Fibrosis; Rats, Sprague-Dawley; Signal Transduction

The aim of the current study is determination of protective effect of chrysin (CRS), a natural flavonoid, on cell injury produced by lung fibrosis induced with bleomycin (BLC) in rats. Twenty-eight female rats were assigned to four groups as follows: control group, CRS group; 50 mg/kg CRS was continued orally for 14 days, BLC group; a single intratracheal injection of BLC (2.5 mg/kg body weight in 0.25 ml phosphate buffered saline), BLC + CRS group; 50 mg/kg CRS was administered 1 day before the intratracheal BLC injection and continued for 14 days orally. All animals were sacrificed at day 14th after BLC administration. The semiquantitative assessment of histopathological consisting of lung inflammation and collagen deposition, tissue levels of thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reducted glutathione (GSH) were measured. BLC provoked histological changes consisting of alveolar congestion, increase connective tissue, infiltration, and the thickness of alveolar wall were detected significantly when compared to the control group (p ≤ 0.0001). CRS supplementation significantly restored these histological damages (p ≤ 0.0001). The level of tissue TBARS was increased with BLC (p < 0.01). Increased level of TBARS was significantly reversed by CRS administration. Also, BLC administration reduced tissue activities of SOD, GPx, CAT, and GSH in the lung tissue compared to control group (p < 0.01). Furthermore, the reduction in activities of CAT, SOD, and level of GSH were prevented by CRS supplementation (p < 0.01). In this study, we demonstrated for the first time that CRS significantly prevents BLC-induced lung inflammation and fibrosis in rats. Further studies are needed to assess the role of CRS in the treatment of lung inflammation and fibrosis.

Topics: Animals; Antioxidants; Bleomycin; Female; Flavonoids; Oxidative Stress; Pulmonary Fibrosis; Rats; Rats, Wistar