Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease
: Background/Aims: This study sought to determine whether excess hepatic iron potentiates liver injury in the methionine choline‐deficient (MCD) model of non‐alcoholic fatty liver disease (NAFLD). Methods: Iron‐loaded rats were fed either MCD or control diets [MCD diet plus choline bitartrate (2 g/k...
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| Veröffentlicht in: | Liver international 2006-12, Vol.26 (10), p.1258-1267 |
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| container_title | Liver international |
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| creator | Kirsch, Richard Sijtsema, Helene P. Tlali, Mpho Marais, Adrian D. Hall, Pauline de la M |
| description | : Background/Aims: This study sought to determine whether excess hepatic iron potentiates liver injury in the methionine choline‐deficient (MCD) model of non‐alcoholic fatty liver disease (NAFLD).
Methods: Iron‐loaded rats were fed either MCD or control diets [MCD diet plus choline bitartrate (2 g/kg) and dl‐methionine (3 g/kg)] for 4 and 12 weeks, after which liver pathology, hepatic iron, triglyceride, lipid peroxidation products and hydroxyproline (HYP) levels and serum alanine aminotransferase (ALT) levels were evaluated.
Results: Iron supplementation in MCD animals resulted in histologic evidence of hepatic iron overload at 4 and 12 weeks and a 14‐fold increase in hepatic iron concentration at 12 weeks (P |
| doi_str_mv | 10.1111/j.1478-3231.2006.01329.x |
| format | Article |
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Methods: Iron‐loaded rats were fed either MCD or control diets [MCD diet plus choline bitartrate (2 g/kg) and dl‐methionine (3 g/kg)] for 4 and 12 weeks, after which liver pathology, hepatic iron, triglyceride, lipid peroxidation products and hydroxyproline (HYP) levels and serum alanine aminotransferase (ALT) levels were evaluated.
Results: Iron supplementation in MCD animals resulted in histologic evidence of hepatic iron overload at 4 and 12 weeks and a 14‐fold increase in hepatic iron concentration at 12 weeks (P<0.001). Iron supplementation in these animals was associated with increased lobular necroinflammation at 4 weeks (P<0.02) and decreased hepatic steatosis (P<0.01), hepatic triglyceride levels (P<0.01), hepatic‐conjugated dienes (CD; P<0.02) and serum ALT levels (P<0.002) at 12 weeks. Reduced hepatic steatosis (P<0.005) and CD (P<0.01) were apparent by 4 weeks. Iron supplementation was associated with a trend towards increased perivenular fibrosis not hepatic HYP content.
Conclusion: Hepatic iron overload in the MCD model of NAFLD is associated with decreased hepatic lipid, decreased early lipid peroxidation products, increased necroinflammation and a trend towards increased perivenular fibrosis.]]></description><identifier>ISSN: 1478-3223</identifier><identifier>EISSN: 1478-3231</identifier><identifier>DOI: 10.1111/j.1478-3231.2006.01329.x</identifier><identifier>PMID: 17105592</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Alanine Transaminase - blood ; Animals ; Body Weight ; Choline Deficiency - complications ; Disease Models, Animal ; Fatty Liver - etiology ; Fatty Liver - metabolism ; Fatty Liver - pathology ; Female ; fibrosis ; Hydroxyproline - analysis ; inflammation ; iron ; Iron Overload - complications ; Lipid Peroxidation ; Liver - metabolism ; Liver - pathology ; Methionine - deficiency ; methionine choline deficient ; Organ Size ; Rats ; Rats, Inbred F344 ; steatosis</subject><ispartof>Liver international, 2006-12, Vol.26 (10), p.1258-1267</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4719-d94ea6cc90cf73f20676e2bfa8943be411d1edfa93a4d940c46cc82662c0f8ad3</citedby><cites>FETCH-LOGICAL-c4719-d94ea6cc90cf73f20676e2bfa8943be411d1edfa93a4d940c46cc82662c0f8ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1478-3231.2006.01329.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1478-3231.2006.01329.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17105592$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kirsch, Richard</creatorcontrib><creatorcontrib>Sijtsema, Helene P.</creatorcontrib><creatorcontrib>Tlali, Mpho</creatorcontrib><creatorcontrib>Marais, Adrian D.</creatorcontrib><creatorcontrib>Hall, Pauline de la M</creatorcontrib><title>Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease</title><title>Liver international</title><addtitle>Liver Int</addtitle><description><![CDATA[: Background/Aims: This study sought to determine whether excess hepatic iron potentiates liver injury in the methionine choline‐deficient (MCD) model of non‐alcoholic fatty liver disease (NAFLD).
Methods: Iron‐loaded rats were fed either MCD or control diets [MCD diet plus choline bitartrate (2 g/kg) and dl‐methionine (3 g/kg)] for 4 and 12 weeks, after which liver pathology, hepatic iron, triglyceride, lipid peroxidation products and hydroxyproline (HYP) levels and serum alanine aminotransferase (ALT) levels were evaluated.
Results: Iron supplementation in MCD animals resulted in histologic evidence of hepatic iron overload at 4 and 12 weeks and a 14‐fold increase in hepatic iron concentration at 12 weeks (P<0.001). Iron supplementation in these animals was associated with increased lobular necroinflammation at 4 weeks (P<0.02) and decreased hepatic steatosis (P<0.01), hepatic triglyceride levels (P<0.01), hepatic‐conjugated dienes (CD; P<0.02) and serum ALT levels (P<0.002) at 12 weeks. Reduced hepatic steatosis (P<0.005) and CD (P<0.01) were apparent by 4 weeks. Iron supplementation was associated with a trend towards increased perivenular fibrosis not hepatic HYP content.
Conclusion: Hepatic iron overload in the MCD model of NAFLD is associated with decreased hepatic lipid, decreased early lipid peroxidation products, increased necroinflammation and a trend towards increased perivenular fibrosis.]]></description><subject>Alanine Transaminase - blood</subject><subject>Animals</subject><subject>Body Weight</subject><subject>Choline Deficiency - complications</subject><subject>Disease Models, Animal</subject><subject>Fatty Liver - etiology</subject><subject>Fatty Liver - metabolism</subject><subject>Fatty Liver - pathology</subject><subject>Female</subject><subject>fibrosis</subject><subject>Hydroxyproline - analysis</subject><subject>inflammation</subject><subject>iron</subject><subject>Iron Overload - complications</subject><subject>Lipid Peroxidation</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Methionine - deficiency</subject><subject>methionine choline deficient</subject><subject>Organ Size</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>steatosis</subject><issn>1478-3223</issn><issn>1478-3231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMtOGzEUQK2qqLz6C5VX3c3gVzzjBQtKeUkjUFWgFRvL8VwLB2dM7Qkkf88MidIt3vhKPudaOghhSko6nKNZSUVVF5xxWjJCZEkoZ6pcfkJ724fP25nxXbSf84wQqtSEfkG7tKJkMlFsD_09cw5sn3F02KfY4fgCKUTTYt9hg5Ppcbfok-997EzA89hCGNkudoUJNj7G4C12pu9XOPjBxa3PYDIcoh1nQoavm_sA3Z2f3Z5eFs3NxdXpSVNYUVFVtEqAkdYqYl3FHSOyksCmztRK8CkISlsKrTOKGzGwxIoBrpmUzBJXm5YfoO_rvc8p_ltA7vXcZwshmA7iImtZU1ELJQewXoM2xZwTOP2c_NyklaZEj1X1TI_B9BhPj1X1e1W9HNRvmz8W0zm0_8VNxgE4XgOvPsDqw4t1c3U_ToNfrH2fe1hufZOetKx4NdF_ri_0j-Zn8_Dw67em_A1wQ5YN</recordid><startdate>200612</startdate><enddate>200612</enddate><creator>Kirsch, Richard</creator><creator>Sijtsema, Helene P.</creator><creator>Tlali, Mpho</creator><creator>Marais, Adrian D.</creator><creator>Hall, Pauline de la M</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><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>7X8</scope></search><sort><creationdate>200612</creationdate><title>Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease</title><author>Kirsch, Richard ; Sijtsema, Helene P. ; Tlali, Mpho ; Marais, Adrian D. ; Hall, Pauline de la M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4719-d94ea6cc90cf73f20676e2bfa8943be411d1edfa93a4d940c46cc82662c0f8ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Alanine Transaminase - blood</topic><topic>Animals</topic><topic>Body Weight</topic><topic>Choline Deficiency - complications</topic><topic>Disease Models, Animal</topic><topic>Fatty Liver - etiology</topic><topic>Fatty Liver - metabolism</topic><topic>Fatty Liver - pathology</topic><topic>Female</topic><topic>fibrosis</topic><topic>Hydroxyproline - analysis</topic><topic>inflammation</topic><topic>iron</topic><topic>Iron Overload - complications</topic><topic>Lipid Peroxidation</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Methionine - deficiency</topic><topic>methionine choline deficient</topic><topic>Organ Size</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>steatosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kirsch, Richard</creatorcontrib><creatorcontrib>Sijtsema, Helene P.</creatorcontrib><creatorcontrib>Tlali, Mpho</creatorcontrib><creatorcontrib>Marais, Adrian D.</creatorcontrib><creatorcontrib>Hall, Pauline de la M</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Liver international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kirsch, Richard</au><au>Sijtsema, Helene P.</au><au>Tlali, Mpho</au><au>Marais, Adrian D.</au><au>Hall, Pauline de la M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease</atitle><jtitle>Liver international</jtitle><addtitle>Liver Int</addtitle><date>2006-12</date><risdate>2006</risdate><volume>26</volume><issue>10</issue><spage>1258</spage><epage>1267</epage><pages>1258-1267</pages><issn>1478-3223</issn><eissn>1478-3231</eissn><abstract><![CDATA[: Background/Aims: This study sought to determine whether excess hepatic iron potentiates liver injury in the methionine choline‐deficient (MCD) model of non‐alcoholic fatty liver disease (NAFLD).
Methods: Iron‐loaded rats were fed either MCD or control diets [MCD diet plus choline bitartrate (2 g/kg) and dl‐methionine (3 g/kg)] for 4 and 12 weeks, after which liver pathology, hepatic iron, triglyceride, lipid peroxidation products and hydroxyproline (HYP) levels and serum alanine aminotransferase (ALT) levels were evaluated.
Results: Iron supplementation in MCD animals resulted in histologic evidence of hepatic iron overload at 4 and 12 weeks and a 14‐fold increase in hepatic iron concentration at 12 weeks (P<0.001). Iron supplementation in these animals was associated with increased lobular necroinflammation at 4 weeks (P<0.02) and decreased hepatic steatosis (P<0.01), hepatic triglyceride levels (P<0.01), hepatic‐conjugated dienes (CD; P<0.02) and serum ALT levels (P<0.002) at 12 weeks. Reduced hepatic steatosis (P<0.005) and CD (P<0.01) were apparent by 4 weeks. Iron supplementation was associated with a trend towards increased perivenular fibrosis not hepatic HYP content.
Conclusion: Hepatic iron overload in the MCD model of NAFLD is associated with decreased hepatic lipid, decreased early lipid peroxidation products, increased necroinflammation and a trend towards increased perivenular fibrosis.]]></abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>17105592</pmid><doi>10.1111/j.1478-3231.2006.01329.x</doi><tpages>10</tpages></addata></record> |
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| subjects | Alanine Transaminase - blood Animals Body Weight Choline Deficiency - complications Disease Models, Animal Fatty Liver - etiology Fatty Liver - metabolism Fatty Liver - pathology Female fibrosis Hydroxyproline - analysis inflammation iron Iron Overload - complications Lipid Peroxidation Liver - metabolism Liver - pathology Methionine - deficiency methionine choline deficient Organ Size Rats Rats, Inbred F344 steatosis |
| title | Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease |
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