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Effect of Iron Supplementation on the Expression of Hypoxia-Inducible Factor and Antioxidant Status in Rats Exposed to High-Altitude Hypoxia Environment
Iron and oxygen are essential substance for cellular activity in body tissues. Hypoxia-inducible factors (HIFs) can respond to available oxygen changes in the cellular environment and regulate the transcription of a series of target genes. The study was conducted to investigate the effects of iron s...
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| Published in: | Biological trace element research 2014-12, Vol.162 (1-3), p.142-152 |
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| creator | Xu, Chunlan Dong, Chen Xu, Cuicui Han, Tiaotiao Bao, Sheng Gao, Xiaobo |
| description | Iron and oxygen are essential substance for cellular activity in body tissues. Hypoxia-inducible factors (HIFs) can respond to available oxygen changes in the cellular environment and regulate the transcription of a series of target genes. The study was conducted to investigate the effects of iron supplementation on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and antioxidant status in rats exposed to high-altitude hypoxia environment. Forty rats were divided into control (CON), hypobaric hypoxia (HH), and hypobaric hypoxia plus ferrous sulfate (FeSO
4
) (9.93 mg/kg body weight (BW)/day) (HFS) and hypobaric hypoxia plus iron glycinate chelate (Fe-Gly) (11.76 mg/kg BW/day) (HFG) groups. Results showed that Fe-Gly effectively alleviated weight loss and intestinal mucosa damage induced by hypobaric hypoxia, whereas FeSO
4
aggravated hypobaric hypoxia-induced weight loss, liver enlargement, spleen atrophy, and intestinal damage. Iron supplementation decreased liver superoxide dismutase (T-SOD) and catalase (CAT) activity (
P
|
| doi_str_mv | 10.1007/s12011-014-0166-6 |
| format | article |
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4
) (9.93 mg/kg body weight (BW)/day) (HFS) and hypobaric hypoxia plus iron glycinate chelate (Fe-Gly) (11.76 mg/kg BW/day) (HFG) groups. Results showed that Fe-Gly effectively alleviated weight loss and intestinal mucosa damage induced by hypobaric hypoxia, whereas FeSO
4
aggravated hypobaric hypoxia-induced weight loss, liver enlargement, spleen atrophy, and intestinal damage. Iron supplementation decreased liver superoxide dismutase (T-SOD) and catalase (CAT) activity (
P
< 0.01) and increased iron concentration in the liver compared to HH group (
P
< 0.001). Moreover, Fe-Gly upregulated liver transferrin expression in messenger RNA (mRNA) level (
P
< 0.05) and downregulated serum erythropoietin (EPO) concentration (
P
< 0.01) and liver HIF-1α expression level (
P
< 0.05 in mRNA level;
P
< 0.001 in protein level) compared to HH group. The study indicated that FeSO
4
supplementation at high altitudes aggravated the oxidative damage of tissues and organs that could be mediated through production of malondialdehyde (MDA) and inhibition antioxidant enzyme activities. Fe-Gly can protect hypobaric hypoxia-induced tissues injury. Moreover, iron supplementation at high altitudes affected HIF-1α-mediated regulating expression of targeting genes such as EPO and transferrin. The study highlights that iron supplementation under hypobaric hypoxia environment has possible limitation, and efficient supplementation form and dosage need careful consideration.]]></description><identifier>ISSN: 0163-4984</identifier><identifier>EISSN: 1559-0720</identifier><identifier>DOI: 10.1007/s12011-014-0166-6</identifier><identifier>PMID: 25380676</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Altitude ; Animals ; Antioxidants ; Antioxidants - metabolism ; Biochemistry ; Biomedical and Life Sciences ; Biotechnology ; Body weight ; Enzymatic activity ; Erythropoietin - blood ; Ferrous Compounds - therapeutic use ; Hypoxia ; Hypoxia - drug therapy ; Hypoxia-Inducible Factor 1, alpha Subunit - genetics ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Immunohistochemistry ; Iron ; Life Sciences ; Liver ; Liver - metabolism ; Male ; Malondialdehyde - metabolism ; Nutrition ; Oncology ; Protein expression ; Rats ; Rats, Sprague-Dawley ; RNA, Messenger - genetics ; Rodents ; Transferrin - genetics</subject><ispartof>Biological trace element research, 2014-12, Vol.162 (1-3), p.142-152</ispartof><rights>Springer Science+Business Media New York 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-e68f7cd196b5ad0c40999b67d7722caf4508ae4a3f1163461cf968c82f616d5e3</citedby><cites>FETCH-LOGICAL-c442t-e68f7cd196b5ad0c40999b67d7722caf4508ae4a3f1163461cf968c82f616d5e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25380676$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Chunlan</creatorcontrib><creatorcontrib>Dong, Chen</creatorcontrib><creatorcontrib>Xu, Cuicui</creatorcontrib><creatorcontrib>Han, Tiaotiao</creatorcontrib><creatorcontrib>Bao, Sheng</creatorcontrib><creatorcontrib>Gao, Xiaobo</creatorcontrib><title>Effect of Iron Supplementation on the Expression of Hypoxia-Inducible Factor and Antioxidant Status in Rats Exposed to High-Altitude Hypoxia Environment</title><title>Biological trace element research</title><addtitle>Biol Trace Elem Res</addtitle><addtitle>Biol Trace Elem Res</addtitle><description><![CDATA[Iron and oxygen are essential substance for cellular activity in body tissues. Hypoxia-inducible factors (HIFs) can respond to available oxygen changes in the cellular environment and regulate the transcription of a series of target genes. The study was conducted to investigate the effects of iron supplementation on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and antioxidant status in rats exposed to high-altitude hypoxia environment. Forty rats were divided into control (CON), hypobaric hypoxia (HH), and hypobaric hypoxia plus ferrous sulfate (FeSO
4
) (9.93 mg/kg body weight (BW)/day) (HFS) and hypobaric hypoxia plus iron glycinate chelate (Fe-Gly) (11.76 mg/kg BW/day) (HFG) groups. Results showed that Fe-Gly effectively alleviated weight loss and intestinal mucosa damage induced by hypobaric hypoxia, whereas FeSO
4
aggravated hypobaric hypoxia-induced weight loss, liver enlargement, spleen atrophy, and intestinal damage. Iron supplementation decreased liver superoxide dismutase (T-SOD) and catalase (CAT) activity (
P
< 0.01) and increased iron concentration in the liver compared to HH group (
P
< 0.001). Moreover, Fe-Gly upregulated liver transferrin expression in messenger RNA (mRNA) level (
P
< 0.05) and downregulated serum erythropoietin (EPO) concentration (
P
< 0.01) and liver HIF-1α expression level (
P
< 0.05 in mRNA level;
P
< 0.001 in protein level) compared to HH group. The study indicated that FeSO
4
supplementation at high altitudes aggravated the oxidative damage of tissues and organs that could be mediated through production of malondialdehyde (MDA) and inhibition antioxidant enzyme activities. Fe-Gly can protect hypobaric hypoxia-induced tissues injury. Moreover, iron supplementation at high altitudes affected HIF-1α-mediated regulating expression of targeting genes such as EPO and transferrin. The study highlights that iron supplementation under hypobaric hypoxia environment has possible limitation, and efficient supplementation form and dosage need careful consideration.]]></description><subject>Altitude</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Antioxidants - metabolism</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biotechnology</subject><subject>Body weight</subject><subject>Enzymatic activity</subject><subject>Erythropoietin - blood</subject><subject>Ferrous Compounds - therapeutic use</subject><subject>Hypoxia</subject><subject>Hypoxia - drug therapy</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Immunohistochemistry</subject><subject>Iron</subject><subject>Life Sciences</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Malondialdehyde - metabolism</subject><subject>Nutrition</subject><subject>Oncology</subject><subject>Protein expression</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>RNA, Messenger - genetics</subject><subject>Rodents</subject><subject>Transferrin - genetics</subject><issn>0163-4984</issn><issn>1559-0720</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNp1kd9qFDEUxoModq0-gDcS8MabaJLJJJPLpWzdhYJg9Tpk86dNmU3GJCPbN_FxzXRbEUFICOfkd75zOB8Abwn-SDAWnwqhmBCECWuXc8SfgRXpe4mwoPg5WLVkh5gc2Bl4VcodxkRQ2b0EZ7TvBswFX4FfG--dqTB5uMspwut5mkZ3cLHqGlrcTr11cHOcsivlIePh9n5Kx6DRLtrZhP3o4KU2NWWoo4Xr2AqPwepY4XVTmQsMEX7VtSwqqTgLa4LbcHOL1mMNdbbuSRBu4s_QpljavwYvvB6Le_P4noPvl5tvF1t09eXz7mJ9hQxjtCLHBy-MJZLve22xYVhKuefCCkGp0Z71eNCO6c6TtgzGifGSD2agnhNue9edgw8n3SmnH7MrVR1CMW4cdXRpLopwOgxtWT1v6Pt_0Ls059ime6CI6CQnjSInyuRUSnZeTTkcdL5XBKvFNnWyTTXb1GKbWpTfPSrP-4OzfyqefGoAPQGlfcUbl_9q_V_V3wWGo_Y</recordid><startdate>20141201</startdate><enddate>20141201</enddate><creator>Xu, Chunlan</creator><creator>Dong, Chen</creator><creator>Xu, Cuicui</creator><creator>Han, Tiaotiao</creator><creator>Bao, Sheng</creator><creator>Gao, Xiaobo</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QH</scope><scope>7QP</scope><scope>7TN</scope><scope>7U7</scope><scope>7UA</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H97</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L.G</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20141201</creationdate><title>Effect of Iron Supplementation on the Expression of Hypoxia-Inducible Factor and Antioxidant Status in Rats Exposed to High-Altitude Hypoxia Environment</title><author>Xu, Chunlan ; Dong, Chen ; Xu, Cuicui ; Han, Tiaotiao ; Bao, Sheng ; Gao, Xiaobo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-e68f7cd196b5ad0c40999b67d7722caf4508ae4a3f1163461cf968c82f616d5e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Altitude</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Antioxidants - metabolism</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biotechnology</topic><topic>Body weight</topic><topic>Enzymatic activity</topic><topic>Erythropoietin - blood</topic><topic>Ferrous Compounds - therapeutic use</topic><topic>Hypoxia</topic><topic>Hypoxia - drug therapy</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</topic><topic>Immunohistochemistry</topic><topic>Iron</topic><topic>Life Sciences</topic><topic>Liver</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Malondialdehyde - metabolism</topic><topic>Nutrition</topic><topic>Oncology</topic><topic>Protein expression</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>RNA, Messenger - genetics</topic><topic>Rodents</topic><topic>Transferrin - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Chunlan</creatorcontrib><creatorcontrib>Dong, Chen</creatorcontrib><creatorcontrib>Xu, Cuicui</creatorcontrib><creatorcontrib>Han, Tiaotiao</creatorcontrib><creatorcontrib>Bao, Sheng</creatorcontrib><creatorcontrib>Gao, Xiaobo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Aqualine</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Oceanic Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Water Resources Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Biological trace element research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Chunlan</au><au>Dong, Chen</au><au>Xu, Cuicui</au><au>Han, Tiaotiao</au><au>Bao, Sheng</au><au>Gao, Xiaobo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Iron Supplementation on the Expression of Hypoxia-Inducible Factor and Antioxidant Status in Rats Exposed to High-Altitude Hypoxia Environment</atitle><jtitle>Biological trace element research</jtitle><stitle>Biol Trace Elem Res</stitle><addtitle>Biol Trace Elem Res</addtitle><date>2014-12-01</date><risdate>2014</risdate><volume>162</volume><issue>1-3</issue><spage>142</spage><epage>152</epage><pages>142-152</pages><issn>0163-4984</issn><eissn>1559-0720</eissn><abstract><![CDATA[Iron and oxygen are essential substance for cellular activity in body tissues. Hypoxia-inducible factors (HIFs) can respond to available oxygen changes in the cellular environment and regulate the transcription of a series of target genes. The study was conducted to investigate the effects of iron supplementation on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and antioxidant status in rats exposed to high-altitude hypoxia environment. Forty rats were divided into control (CON), hypobaric hypoxia (HH), and hypobaric hypoxia plus ferrous sulfate (FeSO
4
) (9.93 mg/kg body weight (BW)/day) (HFS) and hypobaric hypoxia plus iron glycinate chelate (Fe-Gly) (11.76 mg/kg BW/day) (HFG) groups. Results showed that Fe-Gly effectively alleviated weight loss and intestinal mucosa damage induced by hypobaric hypoxia, whereas FeSO
4
aggravated hypobaric hypoxia-induced weight loss, liver enlargement, spleen atrophy, and intestinal damage. Iron supplementation decreased liver superoxide dismutase (T-SOD) and catalase (CAT) activity (
P
< 0.01) and increased iron concentration in the liver compared to HH group (
P
< 0.001). Moreover, Fe-Gly upregulated liver transferrin expression in messenger RNA (mRNA) level (
P
< 0.05) and downregulated serum erythropoietin (EPO) concentration (
P
< 0.01) and liver HIF-1α expression level (
P
< 0.05 in mRNA level;
P
< 0.001 in protein level) compared to HH group. The study indicated that FeSO
4
supplementation at high altitudes aggravated the oxidative damage of tissues and organs that could be mediated through production of malondialdehyde (MDA) and inhibition antioxidant enzyme activities. Fe-Gly can protect hypobaric hypoxia-induced tissues injury. Moreover, iron supplementation at high altitudes affected HIF-1α-mediated regulating expression of targeting genes such as EPO and transferrin. The study highlights that iron supplementation under hypobaric hypoxia environment has possible limitation, and efficient supplementation form and dosage need careful consideration.]]></abstract><cop>Boston</cop><pub>Springer US</pub><pmid>25380676</pmid><doi>10.1007/s12011-014-0166-6</doi><tpages>11</tpages></addata></record> |
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| ispartof | Biological trace element research, 2014-12, Vol.162 (1-3), p.142-152 |
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| source | Springer Nature |
| subjects | Altitude Animals Antioxidants Antioxidants - metabolism Biochemistry Biomedical and Life Sciences Biotechnology Body weight Enzymatic activity Erythropoietin - blood Ferrous Compounds - therapeutic use Hypoxia Hypoxia - drug therapy Hypoxia-Inducible Factor 1, alpha Subunit - genetics Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Immunohistochemistry Iron Life Sciences Liver Liver - metabolism Male Malondialdehyde - metabolism Nutrition Oncology Protein expression Rats Rats, Sprague-Dawley RNA, Messenger - genetics Rodents Transferrin - genetics |
| title | Effect of Iron Supplementation on the Expression of Hypoxia-Inducible Factor and Antioxidant Status in Rats Exposed to High-Altitude Hypoxia Environment |
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