Induction of heme oxygenase-1 (HO-1) and NAD[P]H : Quinone oxidoreductase 1 (NQO1) by a phenolic antioxidant, butylated hydroxyanisole (BHA) and its metabolite, tert -butylhydroquinone (tBHQ) in primary-cultured human and rat hepatocytes
This study was aimed to investigate the effects of a phenolic antioxidant, butylated hydroxyanisole (BHA) and its metabolite, tert-butylhydroquinone (tBHQ) on the induction of HO-1, NQO1 and Nrf2 proteins and their regulatory mechanisms in primary-cultured hepatocytes. After exposure of BHA and tBHQ...
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| creator | KEUM, Young-Sam HAN, Yong-Hae LIEW, Celine KIM, Jung-Hwan CHANGJIANG XU XIAOLING YUAN SHAKARJIAN, Michael P CHONG, Saeho KONG, Ah-Ng |
| description | This study was aimed to investigate the effects of a phenolic antioxidant, butylated hydroxyanisole (BHA) and its metabolite, tert-butylhydroquinone (tBHQ) on the induction of HO-1, NQO1 and Nrf2 proteins and their regulatory mechanisms in primary-cultured hepatocytes.
After exposure of BHA and tBHQ to primary-cultured rat and human hepatocytes and mouse neonatal fibroblasts (MFs), Western blot, semi-quantitative RT-PCR and microarray analysis were conducted.
Induction of HO-1, NQO1 and Nrf2 proteins and activation of ERK1/2 and JNK1/2 were observed after BHA and tBHQ treatments in primary-cultured rat and human hepatocytes. Semi-quantitative RT-PCR study and microarray analysis revealed that HO-1 and NQO1 were transcriptionally activated in primary-cultured rat hepatocytes and a substantial transcriptional activation, including HO-1 occurred in primary-cultured human hepatocytes after BHA treatment. Whereas BHA failed to induce HO-1 in wild-type and Nrf2 knock-out MFs, tBHQ strongly induced HO-1 in wild-type, but not in Nrf2 knock-out MFs.
Our data demonstrate that both BHA and tBHQ are strong chemical inducers of HO-1, NQO1 and Nrf2 proteins in primary-cultured human and rat hepatocytes with the activation of MAPK ERK1/2 and JNK1/2. However, in MFs, BHA failed to induce HO-1, whereas tBHQ strongly induced HO-1 in Nrf2 wild-type but not in Nrf2 knock-out, suggesting that Nrf2 is indispensable for tBHQ-induced HO-1 in MF. |
| doi_str_mv | 10.1007/s11095-006-9094-2 |
| format | Article |
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After exposure of BHA and tBHQ to primary-cultured rat and human hepatocytes and mouse neonatal fibroblasts (MFs), Western blot, semi-quantitative RT-PCR and microarray analysis were conducted.
Induction of HO-1, NQO1 and Nrf2 proteins and activation of ERK1/2 and JNK1/2 were observed after BHA and tBHQ treatments in primary-cultured rat and human hepatocytes. Semi-quantitative RT-PCR study and microarray analysis revealed that HO-1 and NQO1 were transcriptionally activated in primary-cultured rat hepatocytes and a substantial transcriptional activation, including HO-1 occurred in primary-cultured human hepatocytes after BHA treatment. Whereas BHA failed to induce HO-1 in wild-type and Nrf2 knock-out MFs, tBHQ strongly induced HO-1 in wild-type, but not in Nrf2 knock-out MFs.
Our data demonstrate that both BHA and tBHQ are strong chemical inducers of HO-1, NQO1 and Nrf2 proteins in primary-cultured human and rat hepatocytes with the activation of MAPK ERK1/2 and JNK1/2. However, in MFs, BHA failed to induce HO-1, whereas tBHQ strongly induced HO-1 in Nrf2 wild-type but not in Nrf2 knock-out, suggesting that Nrf2 is indispensable for tBHQ-induced HO-1 in MF.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-006-9094-2</identifier><identifier>PMID: 17048120</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Animals ; Antioxidants ; Antioxidants - pharmacology ; Biological and medical sciences ; Butylated Hydroxyanisole - pharmacology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Enzyme Induction - drug effects ; Enzymes ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Gene Expression Regulation, Enzymologic ; General pharmacology ; Heme Oxygenase-1 - biosynthesis ; Heme Oxygenase-1 - genetics ; Hepatocytes - enzymology ; Humans ; Hydroquinones - pharmacology ; JNK Mitogen-Activated Protein Kinases - metabolism ; Medical sciences ; Metabolism ; Mice ; Mice, Inbred C57BL ; NAD(P)H Dehydrogenase (Quinone) - biosynthesis ; NAD(P)H Dehydrogenase (Quinone) - genetics ; NF-E2-Related Factor 2 - physiology ; Oxygen ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology ; Pharmacology. Drug treatments ; Rats ; Rats, Sprague-Dawley ; Rodents</subject><ispartof>Pharmaceutical research, 2006-11, Vol.23 (11), p.2586-2594</ispartof><rights>2007 INIST-CNRS</rights><rights>Springer Science+Business Media, LLC 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-ad49e3e1314f50674c31a49dcd33177632c45331a839ba39a020c1887731f2783</citedby><cites>FETCH-LOGICAL-c422t-ad49e3e1314f50674c31a49dcd33177632c45331a839ba39a020c1887731f2783</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18319431$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17048120$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KEUM, Young-Sam</creatorcontrib><creatorcontrib>HAN, Yong-Hae</creatorcontrib><creatorcontrib>LIEW, Celine</creatorcontrib><creatorcontrib>KIM, Jung-Hwan</creatorcontrib><creatorcontrib>CHANGJIANG XU</creatorcontrib><creatorcontrib>XIAOLING YUAN</creatorcontrib><creatorcontrib>SHAKARJIAN, Michael P</creatorcontrib><creatorcontrib>CHONG, Saeho</creatorcontrib><creatorcontrib>KONG, Ah-Ng</creatorcontrib><title>Induction of heme oxygenase-1 (HO-1) and NAD[P]H : Quinone oxidoreductase 1 (NQO1) by a phenolic antioxidant, butylated hydroxyanisole (BHA) and its metabolite, tert -butylhydroquinone (tBHQ) in primary-cultured human and rat hepatocytes</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>This study was aimed to investigate the effects of a phenolic antioxidant, butylated hydroxyanisole (BHA) and its metabolite, tert-butylhydroquinone (tBHQ) on the induction of HO-1, NQO1 and Nrf2 proteins and their regulatory mechanisms in primary-cultured hepatocytes.
After exposure of BHA and tBHQ to primary-cultured rat and human hepatocytes and mouse neonatal fibroblasts (MFs), Western blot, semi-quantitative RT-PCR and microarray analysis were conducted.
Induction of HO-1, NQO1 and Nrf2 proteins and activation of ERK1/2 and JNK1/2 were observed after BHA and tBHQ treatments in primary-cultured rat and human hepatocytes. Semi-quantitative RT-PCR study and microarray analysis revealed that HO-1 and NQO1 were transcriptionally activated in primary-cultured rat hepatocytes and a substantial transcriptional activation, including HO-1 occurred in primary-cultured human hepatocytes after BHA treatment. Whereas BHA failed to induce HO-1 in wild-type and Nrf2 knock-out MFs, tBHQ strongly induced HO-1 in wild-type, but not in Nrf2 knock-out MFs.
Our data demonstrate that both BHA and tBHQ are strong chemical inducers of HO-1, NQO1 and Nrf2 proteins in primary-cultured human and rat hepatocytes with the activation of MAPK ERK1/2 and JNK1/2. However, in MFs, BHA failed to induce HO-1, whereas tBHQ strongly induced HO-1 in Nrf2 wild-type but not in Nrf2 knock-out, suggesting that Nrf2 is indispensable for tBHQ-induced HO-1 in MF.</description><subject>Animals</subject><subject>Antioxidants</subject><subject>Antioxidants - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Butylated Hydroxyanisole - pharmacology</subject><subject>Cells, Cultured</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Induction - drug effects</subject><subject>Enzymes</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>General pharmacology</subject><subject>Heme Oxygenase-1 - biosynthesis</subject><subject>Heme Oxygenase-1 - genetics</subject><subject>Hepatocytes - enzymology</subject><subject>Humans</subject><subject>Hydroquinones - pharmacology</subject><subject>JNK Mitogen-Activated Protein Kinases - metabolism</subject><subject>Medical sciences</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>NAD(P)H Dehydrogenase (Quinone) - biosynthesis</subject><subject>NAD(P)H Dehydrogenase (Quinone) - genetics</subject><subject>NF-E2-Related Factor 2 - physiology</subject><subject>Oxygen</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpFkl-L1DAUxYMo7rj6AXyRIAizsNHcJDNp9212_dOFZccBBUGkpGnqdGmTMUnBfmi_g-lMYZ9uAr9zTi4nCL0G-h4olR8CAM1XhNI1yWkuCHuCFrCSPN3Ej6doQSUTJJMCztCLEB4opRnk4jk6A0lFBowu0L9bWw86ts5i1-C96Q12f8ffxqpgCOBlsSVwgZWt8f3m48-vvwp8hXdDa52dwLZ23kz6RONE3--2ia5GrPBhb6zrWp20yT2RaV7iaohjp6Kp8X6sfUpStg2uM3h5XWxOOW0MuDdRVUkdzSWOxkdMjsKj5s-cvozXxe4CtxYffNsrPxI9dHHwk_fQK3s08yqmpQ4qOj1GE16iZ43qgnk1z3P0_fOnbzcFudt-ub3Z3BEtGItE1SI33AAH0azoWgrNQYm81jXnIOWaMy1W6agynleK54oyqiHLpOTQMJnxc_T25HuY3mtCLB_c4G2KLBljaykhYwmCE6S9C8GbppwXKYGWU7_lqd8y9VtO_ZaT5s1sPFS9qR8Vc6EJeDcDKmjVNV5Z3YZHLuPpB3Dg_wGe1634</recordid><startdate>20061101</startdate><enddate>20061101</enddate><creator>KEUM, Young-Sam</creator><creator>HAN, Yong-Hae</creator><creator>LIEW, Celine</creator><creator>KIM, Jung-Hwan</creator><creator>CHANGJIANG XU</creator><creator>XIAOLING YUAN</creator><creator>SHAKARJIAN, Michael P</creator><creator>CHONG, Saeho</creator><creator>KONG, Ah-Ng</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20061101</creationdate><title>Induction of heme oxygenase-1 (HO-1) and NAD[P]H : Quinone oxidoreductase 1 (NQO1) by a phenolic antioxidant, butylated hydroxyanisole (BHA) and its metabolite, tert -butylhydroquinone (tBHQ) in primary-cultured human and rat hepatocytes</title><author>KEUM, Young-Sam ; HAN, Yong-Hae ; LIEW, Celine ; KIM, Jung-Hwan ; CHANGJIANG XU ; XIAOLING YUAN ; SHAKARJIAN, Michael P ; CHONG, Saeho ; KONG, Ah-Ng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-ad49e3e1314f50674c31a49dcd33177632c45331a839ba39a020c1887731f2783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Antioxidants</topic><topic>Antioxidants - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Butylated Hydroxyanisole - pharmacology</topic><topic>Cells, Cultured</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Induction - drug effects</topic><topic>Enzymes</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>General pharmacology</topic><topic>Heme Oxygenase-1 - biosynthesis</topic><topic>Heme Oxygenase-1 - genetics</topic><topic>Hepatocytes - enzymology</topic><topic>Humans</topic><topic>Hydroquinones - pharmacology</topic><topic>JNK Mitogen-Activated Protein Kinases - metabolism</topic><topic>Medical sciences</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>NAD(P)H Dehydrogenase (Quinone) - biosynthesis</topic><topic>NAD(P)H Dehydrogenase (Quinone) - genetics</topic><topic>NF-E2-Related Factor 2 - physiology</topic><topic>Oxygen</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rodents</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KEUM, Young-Sam</creatorcontrib><creatorcontrib>HAN, Yong-Hae</creatorcontrib><creatorcontrib>LIEW, Celine</creatorcontrib><creatorcontrib>KIM, Jung-Hwan</creatorcontrib><creatorcontrib>CHANGJIANG XU</creatorcontrib><creatorcontrib>XIAOLING YUAN</creatorcontrib><creatorcontrib>SHAKARJIAN, Michael P</creatorcontrib><creatorcontrib>CHONG, Saeho</creatorcontrib><creatorcontrib>KONG, Ah-Ng</creatorcontrib><collection>Pascal-Francis</collection><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>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma 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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</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 China</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KEUM, Young-Sam</au><au>HAN, Yong-Hae</au><au>LIEW, Celine</au><au>KIM, Jung-Hwan</au><au>CHANGJIANG XU</au><au>XIAOLING YUAN</au><au>SHAKARJIAN, Michael P</au><au>CHONG, Saeho</au><au>KONG, Ah-Ng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of heme oxygenase-1 (HO-1) and NAD[P]H : Quinone oxidoreductase 1 (NQO1) by a phenolic antioxidant, butylated hydroxyanisole (BHA) and its metabolite, tert -butylhydroquinone (tBHQ) in primary-cultured human and rat hepatocytes</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>2006-11-01</date><risdate>2006</risdate><volume>23</volume><issue>11</issue><spage>2586</spage><epage>2594</epage><pages>2586-2594</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>This study was aimed to investigate the effects of a phenolic antioxidant, butylated hydroxyanisole (BHA) and its metabolite, tert-butylhydroquinone (tBHQ) on the induction of HO-1, NQO1 and Nrf2 proteins and their regulatory mechanisms in primary-cultured hepatocytes.
After exposure of BHA and tBHQ to primary-cultured rat and human hepatocytes and mouse neonatal fibroblasts (MFs), Western blot, semi-quantitative RT-PCR and microarray analysis were conducted.
Induction of HO-1, NQO1 and Nrf2 proteins and activation of ERK1/2 and JNK1/2 were observed after BHA and tBHQ treatments in primary-cultured rat and human hepatocytes. Semi-quantitative RT-PCR study and microarray analysis revealed that HO-1 and NQO1 were transcriptionally activated in primary-cultured rat hepatocytes and a substantial transcriptional activation, including HO-1 occurred in primary-cultured human hepatocytes after BHA treatment. Whereas BHA failed to induce HO-1 in wild-type and Nrf2 knock-out MFs, tBHQ strongly induced HO-1 in wild-type, but not in Nrf2 knock-out MFs.
Our data demonstrate that both BHA and tBHQ are strong chemical inducers of HO-1, NQO1 and Nrf2 proteins in primary-cultured human and rat hepatocytes with the activation of MAPK ERK1/2 and JNK1/2. However, in MFs, BHA failed to induce HO-1, whereas tBHQ strongly induced HO-1 in Nrf2 wild-type but not in Nrf2 knock-out, suggesting that Nrf2 is indispensable for tBHQ-induced HO-1 in MF.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>17048120</pmid><doi>10.1007/s11095-006-9094-2</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0724-8741 |
| ispartof | Pharmaceutical research, 2006-11, Vol.23 (11), p.2586-2594 |
| issn | 0724-8741 1573-904X |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Animals Antioxidants Antioxidants - pharmacology Biological and medical sciences Butylated Hydroxyanisole - pharmacology Cells, Cultured Dose-Response Relationship, Drug Enzyme Induction - drug effects Enzymes Extracellular Signal-Regulated MAP Kinases - metabolism Gene Expression Regulation, Enzymologic General pharmacology Heme Oxygenase-1 - biosynthesis Heme Oxygenase-1 - genetics Hepatocytes - enzymology Humans Hydroquinones - pharmacology JNK Mitogen-Activated Protein Kinases - metabolism Medical sciences Metabolism Mice Mice, Inbred C57BL NAD(P)H Dehydrogenase (Quinone) - biosynthesis NAD(P)H Dehydrogenase (Quinone) - genetics NF-E2-Related Factor 2 - physiology Oxygen Pharmaceutical technology. Pharmaceutical industry Pharmacology Pharmacology. Drug treatments Rats Rats, Sprague-Dawley Rodents |
| title | Induction of heme oxygenase-1 (HO-1) and NAD[P]H : Quinone oxidoreductase 1 (NQO1) by a phenolic antioxidant, butylated hydroxyanisole (BHA) and its metabolite, tert -butylhydroquinone (tBHQ) in primary-cultured human and rat hepatocytes |
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