Microsomal azoreduction and glucuronidation in the metabolism of dimethylaminoazobenzene by the rat liver
1. Enzymic azoreduction of the hepatocarcinogen, N, N- dimethyl-4-aminoazobenzene (DAB) and glucuronidation of its ring-hydroxylation product, 4′-hydroxy-DAB, by hepatic microsomal fractions in vitro were studied during an eight day period of hepatic regeneration following partial hepatectomy in Wis...
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| Veröffentlicht in: | Xenobiotica 1987, Vol.17 (6), p.669-677 |
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| creator | Raza, H. Levine, W. G. Chowdhury, N. Roy Chowdhury, J. Roy |
| description | 1. Enzymic azoreduction of the hepatocarcinogen, N, N- dimethyl-4-aminoazobenzene (DAB) and glucuronidation of its ring-hydroxylation product, 4′-hydroxy-DAB, by hepatic microsomal fractions in vitro were studied during an eight day period of hepatic regeneration following partial hepatectomy in Wistar rats. Azoreduction of DAB and its N-demethylated metabolites did not significantly change during hepatic regeneration in contrast to N-demethylation of these dyes which is profoundly suppressed during regeneration. UDP-Glucuronosyltransferase (UDP-GT) activity towards 4′-hydroxy-DAB was partially depressed during the regeneration period, but the depression was considerably less than that for bilirubin. Transferase activity towards 4-nitrophenol, after initial depression, returned to normal levels after the third day of partial hepatectomy.
2. In Gunn rats, microsomal UDP-GT activity towards bilirubin was undetectable, whereas transferase activity toward 4-nitrophenol was 50% of normal. Addition of diethylnitrosamine (DEN) in vitro restored transferase activity towards 4-nitrophenol to normal levels, but the activity towards bilirubin was unaffected. Gunn rat UDP-GT activity towards 4′-hydroxy-DAB was 25% of normal and was partially activated upon addition of DEN in vitro.
3. Treatment with clofibrate of β-naphthoflavone induced hepatic microsomal bilirubin- and 4-nitrophenol-specific UDP-GT activities, respectively; both agents induced transferase activity towards 4′-hydroxy-DAB. Triiodothyronine, which induces 4′-nitrophenol-specific UDP-GT and depresses bilirubin-specific UDPG, had little effect on 4′-hydroxy-DAB UDP-GT activity.
4. The results indicate that microsomal reductive metabolism of DAB is affected differently from that of its oxidative metabolism during liver regeneration. Glucuronidation of 4′-hydroxy-DAB appears to be catalysed by both bilirubin- and 4-nitrophenolspecific UDP-GT isoforms which are differentially expressed during liver regeneration. |
| doi_str_mv | 10.3109/00498258709043974 |
| format | Article |
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2. In Gunn rats, microsomal UDP-GT activity towards bilirubin was undetectable, whereas transferase activity toward 4-nitrophenol was 50% of normal. Addition of diethylnitrosamine (DEN) in vitro restored transferase activity towards 4-nitrophenol to normal levels, but the activity towards bilirubin was unaffected. Gunn rat UDP-GT activity towards 4′-hydroxy-DAB was 25% of normal and was partially activated upon addition of DEN in vitro.
3. Treatment with clofibrate of β-naphthoflavone induced hepatic microsomal bilirubin- and 4-nitrophenol-specific UDP-GT activities, respectively; both agents induced transferase activity towards 4′-hydroxy-DAB. Triiodothyronine, which induces 4′-nitrophenol-specific UDP-GT and depresses bilirubin-specific UDPG, had little effect on 4′-hydroxy-DAB UDP-GT activity.
4. The results indicate that microsomal reductive metabolism of DAB is affected differently from that of its oxidative metabolism during liver regeneration. Glucuronidation of 4′-hydroxy-DAB appears to be catalysed by both bilirubin- and 4-nitrophenolspecific UDP-GT isoforms which are differentially expressed during liver regeneration.</description><identifier>ISSN: 0049-8254</identifier><identifier>EISSN: 1366-5928</identifier><identifier>DOI: 10.3109/00498258709043974</identifier><identifier>PMID: 3114967</identifier><language>eng</language><publisher>England: Informa UK Ltd</publisher><subject>Animals ; Azo Compounds - metabolism ; Biotransformation ; Enzyme Induction ; Glucuronates - metabolism ; Glucuronosyltransferase - biosynthesis ; Glucuronosyltransferase - metabolism ; Hepatectomy ; In Vitro Techniques ; Male ; Microsomes, Liver - metabolism ; NADH, NADPH Oxidoreductases - biosynthesis ; NADH, NADPH Oxidoreductases - metabolism ; p-Dimethylaminoazobenzene - metabolism ; p-Dimethylaminoazobenzene - pharmacology ; Rats ; Rats, Gunn ; Rats, Inbred Strains</subject><ispartof>Xenobiotica, 1987, Vol.17 (6), p.669-677</ispartof><rights>1987 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 1987</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c401t-b5ef6ce3deeed60eb758db510504dc3c9f73349c5474659b946e80af238ab3ad3</citedby><cites>FETCH-LOGICAL-c401t-b5ef6ce3deeed60eb758db510504dc3c9f73349c5474659b946e80af238ab3ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.3109/00498258709043974$$EPDF$$P50$$Ginformaworld$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.3109/00498258709043974$$EHTML$$P50$$Ginformaworld$$H</linktohtml><link.rule.ids>314,777,781,4010,27904,27905,27906,59626,59732,60415,60521,61200,61235,61381,61416</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3114967$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Raza, H.</creatorcontrib><creatorcontrib>Levine, W. G.</creatorcontrib><creatorcontrib>Chowdhury, N. Roy</creatorcontrib><creatorcontrib>Chowdhury, J. Roy</creatorcontrib><title>Microsomal azoreduction and glucuronidation in the metabolism of dimethylaminoazobenzene by the rat liver</title><title>Xenobiotica</title><addtitle>Xenobiotica</addtitle><description>1. Enzymic azoreduction of the hepatocarcinogen, N, N- dimethyl-4-aminoazobenzene (DAB) and glucuronidation of its ring-hydroxylation product, 4′-hydroxy-DAB, by hepatic microsomal fractions in vitro were studied during an eight day period of hepatic regeneration following partial hepatectomy in Wistar rats. Azoreduction of DAB and its N-demethylated metabolites did not significantly change during hepatic regeneration in contrast to N-demethylation of these dyes which is profoundly suppressed during regeneration. UDP-Glucuronosyltransferase (UDP-GT) activity towards 4′-hydroxy-DAB was partially depressed during the regeneration period, but the depression was considerably less than that for bilirubin. Transferase activity towards 4-nitrophenol, after initial depression, returned to normal levels after the third day of partial hepatectomy.
2. In Gunn rats, microsomal UDP-GT activity towards bilirubin was undetectable, whereas transferase activity toward 4-nitrophenol was 50% of normal. Addition of diethylnitrosamine (DEN) in vitro restored transferase activity towards 4-nitrophenol to normal levels, but the activity towards bilirubin was unaffected. Gunn rat UDP-GT activity towards 4′-hydroxy-DAB was 25% of normal and was partially activated upon addition of DEN in vitro.
3. Treatment with clofibrate of β-naphthoflavone induced hepatic microsomal bilirubin- and 4-nitrophenol-specific UDP-GT activities, respectively; both agents induced transferase activity towards 4′-hydroxy-DAB. Triiodothyronine, which induces 4′-nitrophenol-specific UDP-GT and depresses bilirubin-specific UDPG, had little effect on 4′-hydroxy-DAB UDP-GT activity.
4. The results indicate that microsomal reductive metabolism of DAB is affected differently from that of its oxidative metabolism during liver regeneration. Glucuronidation of 4′-hydroxy-DAB appears to be catalysed by both bilirubin- and 4-nitrophenolspecific UDP-GT isoforms which are differentially expressed during liver regeneration.</description><subject>Animals</subject><subject>Azo Compounds - metabolism</subject><subject>Biotransformation</subject><subject>Enzyme Induction</subject><subject>Glucuronates - metabolism</subject><subject>Glucuronosyltransferase - biosynthesis</subject><subject>Glucuronosyltransferase - metabolism</subject><subject>Hepatectomy</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Microsomes, Liver - metabolism</subject><subject>NADH, NADPH Oxidoreductases - biosynthesis</subject><subject>NADH, NADPH Oxidoreductases - metabolism</subject><subject>p-Dimethylaminoazobenzene - metabolism</subject><subject>p-Dimethylaminoazobenzene - pharmacology</subject><subject>Rats</subject><subject>Rats, Gunn</subject><subject>Rats, Inbred Strains</subject><issn>0049-8254</issn><issn>1366-5928</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1987</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kNtKxDAQhoMouh4ewAshL1BNmvQQ9EbEEyje6HWZJFM3kiaStsru09t1RRDRq2Hmn-9n5ifkkLNjwZk6YUyqOi_qiikmharkBplxUZZZofJ6k8xWejYtyB2y2_cvjLGS5_k22RacS1VWM-LunUmxjx14CsuY0I5mcDFQCJY--9GMKQZn4XPmAh3mSDscQEfv-o7Gllo39fOFh86FOFloDEsMSPXicznBQL17w7RPtlrwPR581T3ydHX5eHGT3T1c316c32VGMj5kusC2NCgsItqSoa6K2uqCs4JJa4RRbSWEVKaQlSwLpZUssWbQ5qIGLcCKPcLXvqu_-oRt85pcB2nRcNasUmt-pTYxR2vmddQd2m_iK6ZJP1vrLrQxdfAek7fNAAsfU5sgGNevrP-2P_2BzxH8MDeQsHmJYwpTHP8c9wFxI5Ar</recordid><startdate>1987</startdate><enddate>1987</enddate><creator>Raza, H.</creator><creator>Levine, W. G.</creator><creator>Chowdhury, N. Roy</creator><creator>Chowdhury, J. Roy</creator><general>Informa UK Ltd</general><general>Taylor & Francis</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></search><sort><creationdate>1987</creationdate><title>Microsomal azoreduction and glucuronidation in the metabolism of dimethylaminoazobenzene by the rat liver</title><author>Raza, H. ; Levine, W. G. ; Chowdhury, N. Roy ; Chowdhury, J. Roy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c401t-b5ef6ce3deeed60eb758db510504dc3c9f73349c5474659b946e80af238ab3ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1987</creationdate><topic>Animals</topic><topic>Azo Compounds - metabolism</topic><topic>Biotransformation</topic><topic>Enzyme Induction</topic><topic>Glucuronates - metabolism</topic><topic>Glucuronosyltransferase - biosynthesis</topic><topic>Glucuronosyltransferase - metabolism</topic><topic>Hepatectomy</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Microsomes, Liver - metabolism</topic><topic>NADH, NADPH Oxidoreductases - biosynthesis</topic><topic>NADH, NADPH Oxidoreductases - metabolism</topic><topic>p-Dimethylaminoazobenzene - metabolism</topic><topic>p-Dimethylaminoazobenzene - pharmacology</topic><topic>Rats</topic><topic>Rats, Gunn</topic><topic>Rats, Inbred Strains</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Raza, H.</creatorcontrib><creatorcontrib>Levine, W. G.</creatorcontrib><creatorcontrib>Chowdhury, N. Roy</creatorcontrib><creatorcontrib>Chowdhury, J. Roy</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Xenobiotica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Raza, H.</au><au>Levine, W. G.</au><au>Chowdhury, N. Roy</au><au>Chowdhury, J. Roy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microsomal azoreduction and glucuronidation in the metabolism of dimethylaminoazobenzene by the rat liver</atitle><jtitle>Xenobiotica</jtitle><addtitle>Xenobiotica</addtitle><date>1987</date><risdate>1987</risdate><volume>17</volume><issue>6</issue><spage>669</spage><epage>677</epage><pages>669-677</pages><issn>0049-8254</issn><eissn>1366-5928</eissn><abstract>1. Enzymic azoreduction of the hepatocarcinogen, N, N- dimethyl-4-aminoazobenzene (DAB) and glucuronidation of its ring-hydroxylation product, 4′-hydroxy-DAB, by hepatic microsomal fractions in vitro were studied during an eight day period of hepatic regeneration following partial hepatectomy in Wistar rats. Azoreduction of DAB and its N-demethylated metabolites did not significantly change during hepatic regeneration in contrast to N-demethylation of these dyes which is profoundly suppressed during regeneration. UDP-Glucuronosyltransferase (UDP-GT) activity towards 4′-hydroxy-DAB was partially depressed during the regeneration period, but the depression was considerably less than that for bilirubin. Transferase activity towards 4-nitrophenol, after initial depression, returned to normal levels after the third day of partial hepatectomy.
2. In Gunn rats, microsomal UDP-GT activity towards bilirubin was undetectable, whereas transferase activity toward 4-nitrophenol was 50% of normal. Addition of diethylnitrosamine (DEN) in vitro restored transferase activity towards 4-nitrophenol to normal levels, but the activity towards bilirubin was unaffected. Gunn rat UDP-GT activity towards 4′-hydroxy-DAB was 25% of normal and was partially activated upon addition of DEN in vitro.
3. Treatment with clofibrate of β-naphthoflavone induced hepatic microsomal bilirubin- and 4-nitrophenol-specific UDP-GT activities, respectively; both agents induced transferase activity towards 4′-hydroxy-DAB. Triiodothyronine, which induces 4′-nitrophenol-specific UDP-GT and depresses bilirubin-specific UDPG, had little effect on 4′-hydroxy-DAB UDP-GT activity.
4. The results indicate that microsomal reductive metabolism of DAB is affected differently from that of its oxidative metabolism during liver regeneration. Glucuronidation of 4′-hydroxy-DAB appears to be catalysed by both bilirubin- and 4-nitrophenolspecific UDP-GT isoforms which are differentially expressed during liver regeneration.</abstract><cop>England</cop><pub>Informa UK Ltd</pub><pmid>3114967</pmid><doi>10.3109/00498258709043974</doi><tpages>9</tpages></addata></record> |
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| identifier | ISSN: 0049-8254 |
| ispartof | Xenobiotica, 1987, Vol.17 (6), p.669-677 |
| issn | 0049-8254 1366-5928 |
| language | eng |
| recordid | cdi_crossref_primary_10_3109_00498258709043974 |
| source | MEDLINE; Taylor & Francis CRKN Medical; Taylor & Francis Journals Complete |
| subjects | Animals Azo Compounds - metabolism Biotransformation Enzyme Induction Glucuronates - metabolism Glucuronosyltransferase - biosynthesis Glucuronosyltransferase - metabolism Hepatectomy In Vitro Techniques Male Microsomes, Liver - metabolism NADH, NADPH Oxidoreductases - biosynthesis NADH, NADPH Oxidoreductases - metabolism p-Dimethylaminoazobenzene - metabolism p-Dimethylaminoazobenzene - pharmacology Rats Rats, Gunn Rats, Inbred Strains |
| title | Microsomal azoreduction and glucuronidation in the metabolism of dimethylaminoazobenzene by the rat liver |
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