Estornut Cristina, Milara Javier, Bayarri María Amparo, Belhadj Nada, Cortijo Julio
Department of Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain.
Pharmacy Unit, University General Hospital Consortium, Valencia, Spain.
Front Pharmacol. 2022 Jan 21;12:794997. doi: 10.3389/fphar.2021.794997. eCollection 2021.
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by an abnormal reepithelialisation, an excessive tissue remodelling and a progressive fibrosis within the alveolar wall that are not due to infection or cancer. Oxidative stress has been proposed as a key molecular process in pulmonary fibrosis development and different components of the redox system are altered in the cellular actors participating in lung fibrosis. To this respect, several activators of the antioxidant machinery and inhibitors of the oxidant species and pathways have been assayed in preclinical and models and in different clinical trials. This review discusses the role of oxidative stress in the development and progression of IPF and its underlying mechanisms as well as the evidence of oxidative stress in human IPF. Finally, we analyze the mechanism of action, the efficacy and the current status of different drugs developed to inhibit the oxidative stress as anti-fibrotic therapy in IPF.
特发性肺纤维化(IPF)是一种慢性间质性肺疾病,其特征为异常的再上皮化、过度的组织重塑以及肺泡壁内的进行性纤维化,且并非由感染或癌症引起。氧化应激被认为是肺纤维化发展过程中的关键分子过程,参与肺纤维化的细胞因子中氧化还原系统的不同成分发生了改变。在这方面,抗氧化机制的几种激活剂以及氧化剂种类和途径的抑制剂已在临床前模型和不同的临床试验中进行了检测。本综述讨论了氧化应激在IPF发生和发展中的作用及其潜在机制,以及人类IPF中氧化应激的证据。最后,我们分析了为抑制氧化应激而开发的不同药物作为IPF抗纤维化治疗的作用机制、疗效和现状。