Pre-treatment of rats with ad-hepcidin prevents iron-induced oxidative stress in the brain

Jing Gong; Fang Du; Zhong Ming Qian; Qian Qian Luo; Yuan Sheng; Wing-Ho Yung; Yan Xin Xu; Ya Ke

doi:10.1016/j.freeradbiomed.2015.11.016

Pre-treatment of rats with ad-hepcidin prevents iron-induced oxidative stress in the brain

Jing Gong, Fang Du, Zhong Ming Qian, Qian Qian Luo, Yuan Sheng, Wing-Ho Yung, Yan Xin Xu, Ya Ke^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

42 Citations (Scopus)

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. © 2015 Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	126-132
Journal	Free Radical Biology and Medicine
Volume	90
DOIs	https://doi.org/10.1016/j.freeradbiomed.2015.11.016
Publication status	Published - 1 Jan 2016
Externally published	Yes

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Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

Research Keywords

Cortex
Hepcidin brain iron
Hippocampus
Iron-overloaded rat
Reactive oxygen species (ROS)
Striatum
Substantia nigra

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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. {\textcopyright} 2015 Elsevier Inc. All rights reserved.",

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AU - Du, Fang

AU - Qian, Zhong Ming

AU - Luo, Qian Qian

AU - Sheng, Yuan

AU - Yung, Wing-Ho

AU - Xu, Yan Xin

AU - Ke, Ya

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PY - 2016/1/1

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N2 - 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. © 2015 Elsevier Inc. All rights reserved.

AB - 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. © 2015 Elsevier Inc. All rights reserved.

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KW - Hepcidin brain iron

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KW - Iron-overloaded rat

KW - Reactive oxygen species (ROS)

KW - Striatum

KW - Substantia nigra

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DO - 10.1016/j.freeradbiomed.2015.11.016

M3 - RGC 21 - Publication in refereed journal

C2 - 26582371

SN - 0891-5849

VL - 90

SP - 126

EP - 132

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

ER -

Pre-treatment of rats with ad-hepcidin prevents iron-induced oxidative stress in the brain

Abstract

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