Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Int Immunopharmacol. 2020 Dec;89(Pt A):107011. doi: 10.1016/j.intimp.2020.107011. Epub 2020 Oct 9.
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.
肺纤维化是一种慢性疾病，其特征是成纤维细胞增殖和炎症细胞浸润，这可能引发局部组织缺氧。在这项研究中，研究了白杨素（50mg/kg/口服）在博莱霉素（BLM）诱导的肺纤维化模型中的作用。白杨素能够降低 BLM 给药相关的死亡率，并通过降低羟脯氨酸含量和转化生长因子-β1（TGF-β1）蛋白表达来改善肺结构和肺纤维化。白杨素表现出抗炎作用，其表现为炎症细胞浸润减少、肺泡/毛细血管屏障通透性下降以及乳酸脱氢酶（LDH）活性降低。白杨素通过降低脂质过氧化、增加超氧化物歧化酶（SOD）活性和还原型谷胱甘肽（GSH）含量来增强抗氧化防御机制，从而表现出强大的抗氧化作用。此外，还评估了白杨素对一氧化氮（NOx）含量的影响，结果表明白杨素降低了 NOx，增加了内皮型一氧化氮合酶（eNOS）的蛋白表达，并降低了诱导型一氧化氮合酶（iNOS）的蛋白表达。白杨素还成功降低了硫氧还蛋白相互作用蛋白（TXNIP），即硫氧还蛋白系统的负调节剂，表现出强大的抗氧化作用。最后，白杨素降低了组织和支气管肺泡灌洗液中缺氧诱导因子 1α（HIF1α）的含量，表明白杨素减轻了局部组织缺氧。总之，这项研究表明，白杨素可能通过其抗炎、抗氧化、抗纤维化作用以及缓解缺氧的作用来减轻 BLM 诱导的肺纤维化。
