Blanco Aline, Fernandes Renata, Guimarães Giuliano Rizzotto, Rigatto Katya
Laboratório de Fisiologia Translacional, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil.
Laboratório de Fisiologia Translacional, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil; Programa de Pós-graduação em Ciências da Saúde, UFCSPA, Porto Alegre, RS, Brazil.
Eur J Pharmacol. 2025 Oct 5;1004:177995. doi: 10.1016/j.ejphar.2025.177995. Epub 2025 Jul 25.
Pulmonary Fibrosis (PF) is an interstitial lung disease in which healthy lung tissue is replaced by scar tissue, mainly composed of mesenchymal cells and extracellular matrix. Studies have demonstrated a crucial role for increased oxidative stress in PF pathogenesis and fibroblast recruitment. Recently, our group demonstrated that treatment with Alamandine (ALA) attenuates the clinical effects of PF in an experimental model. However, its effects on redox balance and pulmonary epithelial cellularity have not yet been investigated. Therefore, this study evaluated the antioxidant potential of ALA and fibroblast presence in the lungs of rats with induced PF and treated with ALA.
To induce PF, Bleomycin was administered to Wistar rats, and treatment with ALA began simultaneously. After 14 days, the animals were euthanized, and their lungs were collected for immunohistochemical and redox state analysis.
ALA reduced the number of mesenchymal cells (P < 0.0001), including myofibroblasts (P < 0.005). Additionally, ALA restored total glutathione levels (P < 0.0001) and antioxidant capacity (P < 0.005), while controlling advanced oxidation protein products (P < 0.05) and fluorescence intensity (P < 0.0001), maintaining values like those of the control group.
Our results showed that ALA helps maintain the pulmonary epithelium in a state close to healthy conditions in an experimental PF model. Additionally, we demonstrated that ALA exhibits antioxidant effects by controlling the production of reactive oxygen species. While further studies are warranted, our findings strongly suggest that ALA could be a promising therapeutic option for treating pulmonary fibrosis.
肺纤维化（PF）是一种间质性肺病，其中健康的肺组织被瘢痕组织取代，瘢痕组织主要由间充质细胞和细胞外基质组成。研究表明，氧化应激增加在PF发病机制和成纤维细胞募集过程中起关键作用。最近，我们团队证明，在实验模型中，阿拉曼丁（ALA）治疗可减轻PF的临床症状。然而，其对氧化还原平衡和肺上皮细胞数量的影响尚未得到研究。因此，本研究评估了ALA对诱导性PF大鼠肺部的抗氧化潜力和成纤维细胞存在情况的影响。
为诱导PF，向Wistar大鼠注射博来霉素，并同时开始用ALA治疗。14天后，对动物实施安乐死，收集其肺部进行免疫组织化学和氧化还原状态分析。
ALA减少了间充质细胞数量（P < 0.0001），包括肌成纤维细胞数量（P < 0.005）。此外，ALA恢复了总谷胱甘肽水平（P < 0.0001）和抗氧化能力（P < 0.005），同时控制了晚期氧化蛋白产物（P < 0.05）和荧光强度（P < 0.0001），使其维持在与对照组相似的值。
我们的结果表明，在实验性PF模型中，ALA有助于使肺上皮维持在接近健康的状态。此外，我们证明ALA通过控制活性氧的产生发挥抗氧化作用。虽然还需要进一步研究，但我们的发现强烈表明，ALA可能是治疗肺纤维化的一种有前景的治疗选择。
