Elhadidy Mona G, Elmasry Ahlam, Elsayed Hassan Reda Hassan, El-Nablaway Mohammad, Hamed Shereen, Elalfy Mahmoud M, Rabei Mohammed R
Department of Medical Physiology, Faculty of Medicine, Mansoura University, Egypt.
Department of Medical Physiology, College of Medicine, Al-Baha University, Saudi Arabia.
Heliyon. 2021 Oct 13;7(10):e08171. doi: 10.1016/j.heliyon.2021.e08171. eCollection 2021 Oct.
This study aimed to explore the potential protective effect of α-lipoic acid on busulfan-induced pulmonary fibrosis in rats.
Eighteen adult male rats were divided into 3 groups; control, busulfan, and busulfan plus α-lipoic acid groups. Lung index ratio, serum level of proinflammatory cytokine were assessed. The activities of antioxidant enzymes and lipid peroxidation products were estimated in the lung tissues in addition to the histopathological analyses. The deposition of the collagen in the lung tissues was evaluated by Sirius red staining. The expressions of α-smooth muscle actin (α-SMA), TNF-α, and Caspase 3 were determined immunohistochemically. The pulmonary expression of COX-2 and NOX-4 mRNA was assessed using qRT-PCR.
Administration of ALA significantly protect the lung against BUS-induced pulmonary fibrosis, besides the upregulation of antioxidants, and downregulation of pro-inflammatory cytokines. Also, it reduced collagen deposition that associated with a decreased expression of α-SMA, TNF-α, and Caspase 3 in the lung tissues. Moreover, ALA significantly upregulated the expression of COX-2 concomitant with the downregulation of elevated NOX-4.
ALA attenuates the lung cytotoxicity of busulfan through its anti-inflammatory, anti-apoptotic, and antifibrotic effects that may be mediated by upregulation of COX-2 and downregulation of NOX-4.
本研究旨在探讨α-硫辛酸对白消安诱导的大鼠肺纤维化的潜在保护作用。
将18只成年雄性大鼠分为3组；对照组、白消安组和白消安加α-硫辛酸组。评估肺指数比、促炎细胞因子的血清水平。除了组织病理学分析外，还测定了肺组织中抗氧化酶的活性和脂质过氧化产物。通过天狼星红染色评估肺组织中胶原蛋白的沉积。免疫组织化学法测定α-平滑肌肌动蛋白（α-SMA）、肿瘤坏死因子-α（TNF-α）和半胱天冬酶3的表达。使用qRT-PCR评估COX-2和NOX-4 mRNA在肺组织中的表达。
给予α-硫辛酸可显著保护肺组织免受白消安诱导的肺纤维化，同时上调抗氧化剂水平，下调促炎细胞因子水平。此外，它减少了与肺组织中α-SMA、TNF-α和半胱天冬酶3表达降低相关的胶原蛋白沉积。此外，α-硫辛酸显著上调COX-2的表达，同时下调升高的NOX-4的表达。
α-硫辛酸通过其抗炎、抗凋亡和抗纤维化作用减轻白消安对肺的细胞毒性，这些作用可能由COX-2的上调和NOX-4的下调介导。
