Induction of hepatic xenobiotic metabolizing enzymes in female Fischer-344 rats following repeated inhalation exposure to decamethylcyclopentasiloxane (D5)
Decamethylcyclopentasiloxane (D5) is a cyclic siloxane with a wide range of commercial applications. The present study was designed to investigate the effects of D5 on the expression and activity of selected rat hepatic phase I and phase II metabolizing enzymes. Female Fischer-344 rats were exposed...
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description | Decamethylcyclopentasiloxane (D5) is a cyclic siloxane with a wide range of commercial applications. The present study was designed to investigate the effects of D5 on the expression and activity of selected rat hepatic phase I and phase II metabolizing enzymes. Female Fischer-344 rats were exposed to 160 ppm D5 vapors (6 h/day, 7 days/week, for 28 days) by whole-body inhalation. Changes in the activity and relative abundance of hepatic microsomal cytochromes P450 (CYP1A, CYP2B, CYP3A, and CYP4A), epoxide hydrolase, and UDP-glucuronosyltransferase (UDPGT) were measured. Repeated inhalation exposure of rats to D5 increased liver size by 16% relative to controls by day 28. During a 14-day post-exposure period, liver size in D5-exposed animals showed significant recovery. Exposure to D5 did not change total hepatic P450, but increased the activity of hepatic NADPH-cytochrome c reductase by 1.4-fold. An evaluation of cytochrome P450 (CYP) enzymes in hepatic microsomes prepared from D5-exposed rats revealed a slight (1.8-fold) increase in 7-ethoxyresorufin O-deethylase (EROD) activity, but no change in immunoreactive CYP1A1/2 protein. A moderate increase (4.2-fold) in both 7-pentoxyresorufin O-depentylase (PROD) activity and immunoreactive CYP2B1/2 protein (3.3-fold) was observed. Testosterone 6beta-hydroxylase activity was also increased (2.4-fold) as was CYP3A1/2 immunoreactive protein. Although a small increase in 11- and 12-hydroxylation of lauric acid was detected, no change in immunoreactive CYP4A levels was measured. Liver microsomal epoxide hydrolase activity and immunoreactive protein increased 1.7- and 1.4-fold, respectively, in the D5-exposed group. UDPGT activity toward chloramphenicol was induced 1.8-fold, while no change in UDPGT activity toward 4-nitrophenol was seen. These results suggest that the profile for enzyme induction following inhalation exposure of female Fischer-344 rats to D5 vapors is similar to that reported for phenobarbital, and therefore D5 may be described as a weak "phenobarbital-like" inducer. |
doi_str_mv | 10.1093/toxsci/50.1.10 |
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M ; CHOUDHURI, S ; WILGA, P. C ; MADAN, A ; BURNS-NAAS, L. A ; GALLAVAN, R. H ; MAST, R. W ; NAAS, D. J ; PARKINSON, A ; MEEKS, R. G</creator><creatorcontrib>MCKIM, J. M ; CHOUDHURI, S ; WILGA, P. C ; MADAN, A ; BURNS-NAAS, L. A ; GALLAVAN, R. H ; MAST, R. W ; NAAS, D. J ; PARKINSON, A ; MEEKS, R. G</creatorcontrib><description>Decamethylcyclopentasiloxane (D5) is a cyclic siloxane with a wide range of commercial applications. The present study was designed to investigate the effects of D5 on the expression and activity of selected rat hepatic phase I and phase II metabolizing enzymes. Female Fischer-344 rats were exposed to 160 ppm D5 vapors (6 h/day, 7 days/week, for 28 days) by whole-body inhalation. Changes in the activity and relative abundance of hepatic microsomal cytochromes P450 (CYP1A, CYP2B, CYP3A, and CYP4A), epoxide hydrolase, and UDP-glucuronosyltransferase (UDPGT) were measured. Repeated inhalation exposure of rats to D5 increased liver size by 16% relative to controls by day 28. During a 14-day post-exposure period, liver size in D5-exposed animals showed significant recovery. Exposure to D5 did not change total hepatic P450, but increased the activity of hepatic NADPH-cytochrome c reductase by 1.4-fold. An evaluation of cytochrome P450 (CYP) enzymes in hepatic microsomes prepared from D5-exposed rats revealed a slight (1.8-fold) increase in 7-ethoxyresorufin O-deethylase (EROD) activity, but no change in immunoreactive CYP1A1/2 protein. A moderate increase (4.2-fold) in both 7-pentoxyresorufin O-depentylase (PROD) activity and immunoreactive CYP2B1/2 protein (3.3-fold) was observed. Testosterone 6beta-hydroxylase activity was also increased (2.4-fold) as was CYP3A1/2 immunoreactive protein. Although a small increase in 11- and 12-hydroxylation of lauric acid was detected, no change in immunoreactive CYP4A levels was measured. Liver microsomal epoxide hydrolase activity and immunoreactive protein increased 1.7- and 1.4-fold, respectively, in the D5-exposed group. UDPGT activity toward chloramphenicol was induced 1.8-fold, while no change in UDPGT activity toward 4-nitrophenol was seen. These results suggest that the profile for enzyme induction following inhalation exposure of female Fischer-344 rats to D5 vapors is similar to that reported for phenobarbital, and therefore D5 may be described as a weak "phenobarbital-like" inducer.</description><identifier>ISSN: 1096-6080</identifier><identifier>EISSN: 1096-0929</identifier><identifier>DOI: 10.1093/toxsci/50.1.10</identifier><identifier>PMID: 10445748</identifier><identifier>CODEN: TOSCF2</identifier><language>eng</language><publisher>Cary, NC: Oxford University Press</publisher><subject>Administration, Inhalation ; Animals ; Biological and medical sciences ; Chemical and industrial products toxicology. Toxic occupational diseases ; Cytochrome P-450 Enzyme System - drug effects ; cytochrome P450 ; decamethylcyclopentasiloxane ; Enzyme Induction - drug effects ; Female ; In Vitro Techniques ; Liver - drug effects ; Liver - enzymology ; Medical sciences ; Microsomes, Liver - drug effects ; Rats ; Rats, Inbred F344 ; Siloxanes - pharmacology ; Time Factors ; Toxicology ; Various organic compounds</subject><ispartof>Toxicological sciences, 1999-07, Vol.50 (1), p.10-19</ispartof><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-457e8ce8008fe49850023c22e18de93fba19fadf0e6229270104fe5aba5667d63</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2004229$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10445748$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MCKIM, J. M</creatorcontrib><creatorcontrib>CHOUDHURI, S</creatorcontrib><creatorcontrib>WILGA, P. C</creatorcontrib><creatorcontrib>MADAN, A</creatorcontrib><creatorcontrib>BURNS-NAAS, L. A</creatorcontrib><creatorcontrib>GALLAVAN, R. H</creatorcontrib><creatorcontrib>MAST, R. W</creatorcontrib><creatorcontrib>NAAS, D. J</creatorcontrib><creatorcontrib>PARKINSON, A</creatorcontrib><creatorcontrib>MEEKS, R. G</creatorcontrib><title>Induction of hepatic xenobiotic metabolizing enzymes in female Fischer-344 rats following repeated inhalation exposure to decamethylcyclopentasiloxane (D5)</title><title>Toxicological sciences</title><addtitle>Toxicol Sci</addtitle><description>Decamethylcyclopentasiloxane (D5) is a cyclic siloxane with a wide range of commercial applications. The present study was designed to investigate the effects of D5 on the expression and activity of selected rat hepatic phase I and phase II metabolizing enzymes. Female Fischer-344 rats were exposed to 160 ppm D5 vapors (6 h/day, 7 days/week, for 28 days) by whole-body inhalation. Changes in the activity and relative abundance of hepatic microsomal cytochromes P450 (CYP1A, CYP2B, CYP3A, and CYP4A), epoxide hydrolase, and UDP-glucuronosyltransferase (UDPGT) were measured. Repeated inhalation exposure of rats to D5 increased liver size by 16% relative to controls by day 28. During a 14-day post-exposure period, liver size in D5-exposed animals showed significant recovery. Exposure to D5 did not change total hepatic P450, but increased the activity of hepatic NADPH-cytochrome c reductase by 1.4-fold. An evaluation of cytochrome P450 (CYP) enzymes in hepatic microsomes prepared from D5-exposed rats revealed a slight (1.8-fold) increase in 7-ethoxyresorufin O-deethylase (EROD) activity, but no change in immunoreactive CYP1A1/2 protein. A moderate increase (4.2-fold) in both 7-pentoxyresorufin O-depentylase (PROD) activity and immunoreactive CYP2B1/2 protein (3.3-fold) was observed. Testosterone 6beta-hydroxylase activity was also increased (2.4-fold) as was CYP3A1/2 immunoreactive protein. Although a small increase in 11- and 12-hydroxylation of lauric acid was detected, no change in immunoreactive CYP4A levels was measured. Liver microsomal epoxide hydrolase activity and immunoreactive protein increased 1.7- and 1.4-fold, respectively, in the D5-exposed group. UDPGT activity toward chloramphenicol was induced 1.8-fold, while no change in UDPGT activity toward 4-nitrophenol was seen. These results suggest that the profile for enzyme induction following inhalation exposure of female Fischer-344 rats to D5 vapors is similar to that reported for phenobarbital, and therefore D5 may be described as a weak "phenobarbital-like" inducer.</description><subject>Administration, Inhalation</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Chemical and industrial products toxicology. Toxic occupational diseases</subject><subject>Cytochrome P-450 Enzyme System - drug effects</subject><subject>cytochrome P450</subject><subject>decamethylcyclopentasiloxane</subject><subject>Enzyme Induction - drug effects</subject><subject>Female</subject><subject>In Vitro Techniques</subject><subject>Liver - drug effects</subject><subject>Liver - enzymology</subject><subject>Medical sciences</subject><subject>Microsomes, Liver - drug effects</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Siloxanes - pharmacology</subject><subject>Time Factors</subject><subject>Toxicology</subject><subject>Various organic compounds</subject><issn>1096-6080</issn><issn>1096-0929</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS1ERUvhyhH5gBAc0tpO4sRHVChUqtQLnKOJM2aNHDvYjrrbv8KfrZddIW49eebp87OfHiFvOLvgTNWXOWyTtpdtWYvwjJwVVVZMCfX8OEvWs1PyMqVfjHEumXpBTjlrmrZr-jPy58ZPq842eBoM3eAC2Wq6RR9GG_bjjBnG4OyD9T8p-ofdjIlaTw3O4JBe26Q3GKu6aWiEnKgJzoX7PRxxQcg4FXoDDv6-gdslpDUizYFOqKG4b3ZO77QLC_oMybqwBY_0w-f24ytyYsAlfH08z8mP6y_fr75Vt3dfb64-3Va6VjxXJQn2GnvGeoON6lvGRK2FQN5PqGozAlcGJsNQCqFEx0p6gy2M0ErZTbI-J-8PvksMv1dMeZhLKnSufCSsaZBKta3o1JMg72qlZCcKeHEAdQwpRTTDEu0McTdwNux7Gw69DW1Zi1AuvD06r-OM03_4oagCvDsCkDQ4E8Frm_5xgrGmhKsfAZfOpSk</recordid><startdate>19990701</startdate><enddate>19990701</enddate><creator>MCKIM, J. M</creator><creator>CHOUDHURI, S</creator><creator>WILGA, P. C</creator><creator>MADAN, A</creator><creator>BURNS-NAAS, L. A</creator><creator>GALLAVAN, R. H</creator><creator>MAST, R. W</creator><creator>NAAS, D. J</creator><creator>PARKINSON, A</creator><creator>MEEKS, R. G</creator><general>Oxford University Press</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>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>19990701</creationdate><title>Induction of hepatic xenobiotic metabolizing enzymes in female Fischer-344 rats following repeated inhalation exposure to decamethylcyclopentasiloxane (D5)</title><author>MCKIM, J. M ; CHOUDHURI, S ; WILGA, P. C ; MADAN, A ; BURNS-NAAS, L. A ; GALLAVAN, R. H ; MAST, R. W ; NAAS, D. J ; PARKINSON, A ; MEEKS, R. 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Toxic occupational diseases</topic><topic>Cytochrome P-450 Enzyme System - drug effects</topic><topic>cytochrome P450</topic><topic>decamethylcyclopentasiloxane</topic><topic>Enzyme Induction - drug effects</topic><topic>Female</topic><topic>In Vitro Techniques</topic><topic>Liver - drug effects</topic><topic>Liver - enzymology</topic><topic>Medical sciences</topic><topic>Microsomes, Liver - drug effects</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Siloxanes - pharmacology</topic><topic>Time Factors</topic><topic>Toxicology</topic><topic>Various organic compounds</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MCKIM, J. M</creatorcontrib><creatorcontrib>CHOUDHURI, S</creatorcontrib><creatorcontrib>WILGA, P. C</creatorcontrib><creatorcontrib>MADAN, A</creatorcontrib><creatorcontrib>BURNS-NAAS, L. A</creatorcontrib><creatorcontrib>GALLAVAN, R. H</creatorcontrib><creatorcontrib>MAST, R. W</creatorcontrib><creatorcontrib>NAAS, D. J</creatorcontrib><creatorcontrib>PARKINSON, A</creatorcontrib><creatorcontrib>MEEKS, R. G</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Toxicological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MCKIM, J. M</au><au>CHOUDHURI, S</au><au>WILGA, P. C</au><au>MADAN, A</au><au>BURNS-NAAS, L. A</au><au>GALLAVAN, R. H</au><au>MAST, R. W</au><au>NAAS, D. J</au><au>PARKINSON, A</au><au>MEEKS, R. G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of hepatic xenobiotic metabolizing enzymes in female Fischer-344 rats following repeated inhalation exposure to decamethylcyclopentasiloxane (D5)</atitle><jtitle>Toxicological sciences</jtitle><addtitle>Toxicol Sci</addtitle><date>1999-07-01</date><risdate>1999</risdate><volume>50</volume><issue>1</issue><spage>10</spage><epage>19</epage><pages>10-19</pages><issn>1096-6080</issn><eissn>1096-0929</eissn><coden>TOSCF2</coden><abstract>Decamethylcyclopentasiloxane (D5) is a cyclic siloxane with a wide range of commercial applications. The present study was designed to investigate the effects of D5 on the expression and activity of selected rat hepatic phase I and phase II metabolizing enzymes. Female Fischer-344 rats were exposed to 160 ppm D5 vapors (6 h/day, 7 days/week, for 28 days) by whole-body inhalation. Changes in the activity and relative abundance of hepatic microsomal cytochromes P450 (CYP1A, CYP2B, CYP3A, and CYP4A), epoxide hydrolase, and UDP-glucuronosyltransferase (UDPGT) were measured. Repeated inhalation exposure of rats to D5 increased liver size by 16% relative to controls by day 28. During a 14-day post-exposure period, liver size in D5-exposed animals showed significant recovery. Exposure to D5 did not change total hepatic P450, but increased the activity of hepatic NADPH-cytochrome c reductase by 1.4-fold. An evaluation of cytochrome P450 (CYP) enzymes in hepatic microsomes prepared from D5-exposed rats revealed a slight (1.8-fold) increase in 7-ethoxyresorufin O-deethylase (EROD) activity, but no change in immunoreactive CYP1A1/2 protein. A moderate increase (4.2-fold) in both 7-pentoxyresorufin O-depentylase (PROD) activity and immunoreactive CYP2B1/2 protein (3.3-fold) was observed. Testosterone 6beta-hydroxylase activity was also increased (2.4-fold) as was CYP3A1/2 immunoreactive protein. Although a small increase in 11- and 12-hydroxylation of lauric acid was detected, no change in immunoreactive CYP4A levels was measured. Liver microsomal epoxide hydrolase activity and immunoreactive protein increased 1.7- and 1.4-fold, respectively, in the D5-exposed group. UDPGT activity toward chloramphenicol was induced 1.8-fold, while no change in UDPGT activity toward 4-nitrophenol was seen. These results suggest that the profile for enzyme induction following inhalation exposure of female Fischer-344 rats to D5 vapors is similar to that reported for phenobarbital, and therefore D5 may be described as a weak "phenobarbital-like" inducer.</abstract><cop>Cary, NC</cop><pub>Oxford University Press</pub><pmid>10445748</pmid><doi>10.1093/toxsci/50.1.10</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Administration, Inhalation Animals Biological and medical sciences Chemical and industrial products toxicology. Toxic occupational diseases Cytochrome P-450 Enzyme System - drug effects cytochrome P450 decamethylcyclopentasiloxane Enzyme Induction - drug effects Female In Vitro Techniques Liver - drug effects Liver - enzymology Medical sciences Microsomes, Liver - drug effects Rats Rats, Inbred F344 Siloxanes - pharmacology Time Factors Toxicology Various organic compounds |
title | Induction of hepatic xenobiotic metabolizing enzymes in female Fischer-344 rats following repeated inhalation exposure to decamethylcyclopentasiloxane (D5) |
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