Department of Therapeutic Chemistry, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, 12622, Egypt.
Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
Mol Cell Biochem. 2021 Sep;476(9):3433-3448. doi: 10.1007/s11010-021-04173-7. Epub 2021 May 10.
Amiodarone (AMD) is a widely used antiarrhythmic drug prescribed to treat cardiac tachyarrhythmias; however, AMD has been reported to provoke pulmonary fibrosis (PF) and hepatotoxicity. This study aimed to investigate the influence of alpha lipoic acid (ALA) on AMD-induced PF and hepatotoxicity in male Wistar rats. AMD administration resulted in elevated lung contents of hydroxyproline (Hyp), malondialdehyde (MDA), and increased serum levels of transforming growth factor beta-1 (TGF-β1), interferon-γ (IFN-γ), alanine amino transaminase (ALT), aspartate amino transaminase (AST), total cholesterol (TC), and glucose. On the other side, lung content of glutathione reduced (GSH) and serum levels of total anti-oxidant capacity (TAC) were significantly decreased. Histopathologically, AMD caused PF, produced a mild hepatic injury, and increased expression of alpha smooth muscle actin (α-SMA). Treatment with ALA produced a significant reversal of the oxidative stress, fibrosis, and inflammation parameters with reductions in α-SMA expressions, leading to amelioration of histopathological lesions. ALA might provide supportive therapy in AMD-receiving cardiovascular patients.
胺碘酮（AMD）是一种广泛应用于治疗心脏性心动过速的抗心律失常药物；然而，已有报道称 AMD 可引起肺纤维化（PF）和肝毒性。本研究旨在探讨α-硫辛酸（ALA）对雄性 Wistar 大鼠 AMD 诱导的 PF 和肝毒性的影响。AMD 给药导致羟脯氨酸（Hyp）、丙二醛（MDA）含量增加，转化生长因子-β1（TGF-β1）、干扰素-γ（IFN-γ）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆固醇（TC）和葡萄糖水平升高。另一方面，谷胱甘肽还原（GSH）含量降低，总抗氧化能力（TAC）水平降低。组织病理学检查显示，AMD 引起 PF，产生轻度肝损伤，并增加α-平滑肌肌动蛋白（α-SMA）的表达。ALA 治疗可显著逆转氧化应激、纤维化和炎症参数，降低 α-SMA 的表达，从而改善组织病理学病变。ALA 可能为接受 AMD 治疗的心血管患者提供支持性治疗。
