title: Mechanism of chronic dietary iron overload-induced liver damage in mice.
abstract: 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.
authors: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, P.R. China.
authors: Dan
authors: D
authors: Liu
authors: Huan
authors: H
authors: He
authors: Dong
authors: D
authors: Yin
authors: Ailing
authors: A
authors: Que
authors: Lei
authors: L
authors: Tang
authors: Zhangping
authors: Z
authors: Liao
authors: Qiren
authors: Q
authors: Huang
authors: Ming
authors: M
authors: He
mesh_terms: D000818:Animals; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000378:metabolism* / Q000473:pathology; D019587:Dietary Supplements / Q000009:adverse effects*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007501:Iron / Q000008:administration & dosage / Q000009:adverse effects; D019190:Iron Overload / Q000378:metabolism / Q000473:pathology*; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000633:toxicity; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D007501:Iron; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase