State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, P.R. China.
Mol Med Rep. 2013 Apr;7(4):1173-9. doi: 10.3892/mmr.2013.1316. Epub 2013 Feb 8.
Chronic iron overload may result in hepatic fibrosis and even neoplastic transformation due to a burst of reactive oxygen species (ROS). Mitochondria have been proposed to be important in the production of ROS. The purpose of this study was to investigate the role of the mitochondrial permeability transition pore (mPTP) in the burst of ROS, and to clarify the mechanism whereby ROS induced by iron overload results in hepatic damage. It has been demonstrated that when ferrocene-induced iron-overloaded mice were fed the cyclosporin A (CsA), a specific inhibitor of the mPTP, diet (10 mg/kg/day) for 50 days, liver-to-body weight ratio, serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), ROS production, mitochondrial swelling, loss of mitochondrial membrane potential (Δψ) and hepatocyte apoptosis decreased. However, the total antioxidant status, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase activities, increased. The protective effect of CsA on the liver of iron-overloaded mice may be due to inhibition of the ROS burst and a successive antioxidant effect. To the best of our knowledge, these data provide the first support for the theory that ROS-induced ROS release (RIRR) may be involved in the burst of ROS in the liver and greatly contribute to the hepatic damage initiated by iron overload.
慢性铁过载可导致肝纤维化，甚至肿瘤转化，这是由于活性氧（ROS）的爆发。线粒体被认为在 ROS 的产生中很重要。本研究旨在探讨线粒体通透性转换孔（mPTP）在 ROS 爆发中的作用，并阐明铁过载引起的 ROS 导致肝损伤的机制。已经证明，当用二茂铁诱导铁过载的小鼠喂食环孢菌素 A（CsA），一种 mPTP 的特异性抑制剂，饮食（10mg/kg/天）50 天，肝体比、血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平、ROS 产生、线粒体肿胀、线粒体膜电位（Δψ）丧失和肝细胞凋亡减少。然而，总抗氧化状态，包括超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶活性增加。CsA 对铁过载小鼠肝脏的保护作用可能是由于抑制了 ROS 的爆发和连续的抗氧化作用。据我们所知，这些数据首次为 ROS 诱导的 ROS 释放（RIRR）可能参与肝脏中 ROS 的爆发，并极大地促进铁过载引起的肝损伤的理论提供了支持。
