title: Pre-treatment of rats with ad-hepcidin prevents iron-induced oxidative stress in the brain.
abstract: Our recent investigation showed that hepcidin can reduce iron in the brain of iron-overloaded rat by down-regulating iron-transport proteins. It has also been demonstrated that iron is a major generator of reactive oxygen species. We therefore hypothesized that hepcidin could prevent iron accumulation and thus reduce iron-mediated oxidative stress in iron-overloaded rats. To test this hypothesis, we investigated the effects of pre-treatment of rats with recombinant-hepcidin-adenovirus (ad-hepcidin) on the contents of iron, dichlorofluorescein and 8-isoprostane in the brain. Hepcidin expression was detected by real-time PCR and immunofluorescence analysis. Iron contents were measured using Perl's staining as well as graphite furnace atomic absorption spectrophotometry. Dichlorofluorescein and 8-isoprostane were determined using a fluorescence spectrophotometer and an ELISA kit, respectively. We found that hepcidin contents in the cortex, hippocampus, striatum and substantia nigra of rats treated with ad-hepcidin are 3.50, 2.98, 2.93 and 4.07 fold of those of the control rats respectively. Also, we demonstrated that the increased iron as well as dichlorofluorescein and 8-isoprostane levels in all four brain regions, induced by injection of iron dextran, could be effectively prevented by pre-treatment of the rats with ad-hepcidin. We concluded that pre-treatment with ad-hepcidin could increase hepcidin expression and prevent the increase in iron and reduce reactive oxygen species in the brain of iron-overloaded rats.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, PR China; Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Shanghai 201203, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gong
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong; Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Shanghai 201203, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Du
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, PR China; Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Shanghai 201203, PR China. Electronic address: qianzhongming@fudan.edu.cn.
authors.forename: Zhong Ming
authors.initials: ZM
authors.lastname: Qian
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Shanghai 201203, PR China.
authors.forename: Qian Qian
authors.initials: QQ
authors.lastname: Luo
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Shanghai 201203, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors.forename: Wing-Ho
authors.initials: WH
authors.lastname: Yung
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, PR China.
authors.forename: Yan Xin
authors.initials: YX
authors.lastname: Xu
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong. Electronic address: yake@cuhk.edu.hk.
authors.forename: Ya
authors.initials: Y
authors.lastname: Ke
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000032:analysis; D005452:Fluoresceins / Q000032:analysis; D064451:Hepcidins / Q000494:pharmacology*; D007501:Iron / Q000494:pharmacology*; D019190:Iron Overload / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D005452:Fluoresceins; D064451:Hepcidins; D011994:Recombinant Proteins; C075750:8-epi-prostaglandin F2alpha; C037631:2',7'-dichlorofluorescein; D015237:Dinoprost; D007501:Iron
keywords: Cortex; Hepcidin, brain iron; Hippocampus; Iron-overloaded rat; Reactive oxygen species (ROS); Striatum; Substantia nigra