Mechanism of chronic dietary iron overload‑induced liver damage in mice

Liu,Dan; He,Huan; Yin,Dong; Que,Ailing; Tang,Lei; Liao,Zhangping; Huang,Qiren; He,Ming

doi:10.3892/mmr.2013.1316

Mechanism of chronic dietary iron overload‑induced liver damage in mice

Authors:
- Dan Liu
- Huan He
- Dong Yin
- Ailing Que
- Lei Tang
- Zhangping Liao
- Qiren Huang
- Ming He
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Affiliations: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, P.R. China, Department of Pharmacology and Molecular Therapeutics, Nanchang University School of Pharmaceutical Science, Nanchang 330006, P.R. China, Jiangxi Provincial Key Laboratory of Molecular Medicine, Second Affiliated Hospital of Nanchang University, Nanchang 330006, P.R. China
Published online on: February 8, 2013 https://doi.org/10.3892/mmr.2013.1316
Pages: 1173-1179

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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.

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