Department of Molecular Medicine, 37508Dokuz Eylul University, Health Sciences Institute, Izmir, Turkey.
Department of Internal Medicine, Division of Nephrology, 37508Dokuz Eylul University, School of Medicine, Izmir, Turkey.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271211065975. doi: 10.1177/09603271211065975.
The aim of this study was to determine the protective effects of alpha-lipoic acid (ALA), which is known as a powerful antioxidant, and the possible related molecular mechanisms that mediate its favorable action on skin fibrosis in the bleomycin (BLM)-induced scleroderma (SSc) model in mice. The experimental design was established with four groups of eight mice: Control, ALA (100 mg/kg), BLM (5 μg/kg), and BLM + ALA group. BLM was administered via subcutaneous () once a day while ALA was injected intraperitoneally () twice a week for 21 days. Histopathological and biochemical analyses showed that ALA significantly reduced BLM-induced dermal thickness, inflammation score, and mRNA expression of tumor necrosis factor-alpha (TNF-α) in the skin. Besides, the mRNA expressions of the subunits of NADPH oxidase, which are Nox4 and p22phox, were found to be significantly induced in the BLM group. However, ALA significantly reduced their mRNA expression, which were in parallel to its decreasing effect on serum total oxidant status (TOS) level. Moreover, it was found that ALA downregulated the mRNA expressions of alpha-smooth muscle actin (α-SMA), collagen type I and fibronectin in the skin tissue of the BLM group. Additionally, it was shown that ALA reduced significantly the TGF-β1 and p-Smad3 protein expressions in the BLM + ALA group. On the other hand, ALA did not exhibit any significant effect on the p38 mitogen-activated kinase (MAPK) activation induced by BLM. All these findings point out that ALA may be a promising treatment for the attenuation of skin fibrosis in SSc patients.
本研究旨在确定α-硫辛酸（ALA）的保护作用，AL A 作为一种强大的抗氧化剂，以及介导其对博莱霉素（BLM）诱导的小鼠硬皮病（SSc）模型中皮肤纤维化有利作用的可能相关分子机制。实验设计建立了四组八只小鼠：对照组、ALA（100mg/kg）、BLM（5μg/kg）和 BLM+ALA 组。BLM 通过皮下（）每天一次给药，而 ALA 通过腹腔内（）每周两次注射，共 21 天。组织病理学和生化分析表明，ALA 显著降低了 BLM 诱导的皮肤厚度、炎症评分和 TNF-αmRNA 表达。此外，还发现 NADPH 氧化酶的亚基 Nox4 和 p22phox 的 mRNA 表达在 BLM 组中显著诱导。然而，ALA 显著降低了它们的 mRNA 表达，这与其降低血清总氧化状态（TOS）水平的作用平行。此外，发现 ALA 下调了 BLM 组皮肤组织中α-平滑肌肌动蛋白（α-SMA）、I 型胶原和纤维连接蛋白的 mRNA 表达。此外，还表明 ALA 显著降低了 BLM+ALA 组中 TGF-β1 和 p-Smad3 蛋白的表达。另一方面，ALA 对 BLM 诱导的 p38 丝裂原激活蛋白激酶（MAPK）激活没有显示出任何显著影响。所有这些发现都表明，ALA 可能是治疗 SSc 患者皮肤纤维化的一种有前途的方法。
