Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
Sci Rep. 2024 Apr 16;14(1):8729. doi: 10.1038/s41598-024-59395-8.
Pirfenidone (PFD), one acceptable medication for treating idiopathic pulmonary fibrosis (IPF), is not well tolerated by patients at full doses. Hence, employing of some approaches such as combination therapy may be applicable for increasing therapeutic efficacy of PFD. Losartan (LOS), an angiotensin II receptor antagonist, could be a suitable candidate for combination therapy because of its stabilizing effect on the pulmonary function of IPF patients. Therefore, this study aimed to investigate the effects of LOS in combination with PFD on bleomycin (BLM)-induced lung fibrosis in rats. BLM-exposed rats were treated with LOS alone or in combination with PFD. The edema, pathological changes, level of transforming growth factor-β (TGF-β1), collagen content, and oxidative stress parameters were assessed in the lung tissues. Following BLM exposure, the inflammatory response, collagen levels, and antioxidant markers in rat lung tissues were significantly improved by PFD, and these effects were improved by combination with LOS. The findings of this in vivo study suggest that the combined administration of PFD and LOS may provide more potent protection against IPF than single therapy through boosting its anti-inflammatory, anti-fibrotic, and anti-oxidant effects. These results hold promise in developing a more effective therapeutic strategy for treating of lung fibrosis.
吡非尼酮(PFD)是一种可用于治疗特发性肺纤维化(IPF)的药物,但患者不能耐受全剂量用药。因此,采用联合治疗等方法可能有助于提高 PFD 的治疗效果。氯沙坦(LOS)是一种血管紧张素 II 受体拮抗剂,由于其对 IPF 患者肺功能具有稳定作用,因此可能是联合治疗的合适候选药物。因此,本研究旨在探讨 LOS 与 PFD 联合用药对博来霉素(BLM)诱导的大鼠肺纤维化的影响。BLM 暴露的大鼠单独或联合使用 LOS 进行治疗。评估肺组织中的水肿、病理变化、转化生长因子-β(TGF-β1)水平、胶原含量和氧化应激参数。BLM 暴露后,PFD 显著改善了大鼠肺组织中的炎症反应、胶原水平和抗氧化标志物,联合使用 LOS 可进一步改善这些效果。这项体内研究的结果表明,与单一治疗相比,PFD 和 LOS 的联合给药可能通过增强其抗炎、抗纤维化和抗氧化作用,为治疗肺纤维化提供更有效的治疗策略。