Effect of Pyrethrins on cytochrome P450 forms in cultured rat and human hepatocytes
Abstract High doses of Pyrethrins produce liver and thyroid gland tumours in rats by modes of action involving the induction of hepatic xenobiotic metabolising enzymes. The aim of this study was to compare the effects of Pyrethrins with those of the rat liver and thyroid tumour promoter sodium Pheno...
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| Veröffentlicht in: | Toxicology (Amsterdam) 2008-01, Vol.243 (1), p.84-95 |
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| creator | Price, Roger J Giddings, Amanda M Scott, Mary P Walters, David G Capen, Charles C Osimitz, Thomas G Lake, Brian G |
| description | Abstract High doses of Pyrethrins produce liver and thyroid gland tumours in rats by modes of action involving the induction of hepatic xenobiotic metabolising enzymes. The aim of this study was to compare the effects of Pyrethrins with those of the rat liver and thyroid tumour promoter sodium Phenobarbital on some cytochrome P450 (CYP) forms in cultured rat and human hepatocytes. The treatment of female Sprague–Dawley rat and human (both male and female) hepatocytes for 72 h with 0–1000 μM Pyrethrins and 0–1000 μM Phenobarbital did not result in any marked cytotoxicity. In rat hepatocytes both Pyrethrins and Phenobarbital produced an induction of 7-benzyloxy-4-trifluoromethylcoumarin O -debenzylase activity (a CYP1A/2B form marker) and CYP2B1 and CYP2B1/2 mRNA levels. Pyrethrins and Phenobarbital also induced CYP3A-dependent testosterone 6β-hydroxylase activity in rat hepatocytes. In human hepatocytes Pyrethrins and Phenobarbital induced both testosterone 6β-hydroxylase activity and CYP3A4 mRNA levels and also increased CYP2B6 mRNA levels. The effects of Pyrethrins and Phenobarbital were concentration-dependent and exhibited a threshold. These results demonstrate that the effects of Pyrethrins on CYP forms in cultured rat and human hepatocytes are qualitatively similar to those of Phenobarbital. Pyrethrins induce CYP2B and CYP3A forms in cultured rat hepatocytes and can induce CYP3A and CYP2B forms in human hepatocytes. While CYP form induction by Pyrethrins, Phenobarbital and related compounds can be associated with liver and thyroid gland tumour formation in rodents, epidemiological data for Phenobarbital suggests that such effects do not occur in humans. |
| doi_str_mv | 10.1016/j.tox.2007.09.031 |
| format | Article |
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The aim of this study was to compare the effects of Pyrethrins with those of the rat liver and thyroid tumour promoter sodium Phenobarbital on some cytochrome P450 (CYP) forms in cultured rat and human hepatocytes. The treatment of female Sprague–Dawley rat and human (both male and female) hepatocytes for 72 h with 0–1000 μM Pyrethrins and 0–1000 μM Phenobarbital did not result in any marked cytotoxicity. In rat hepatocytes both Pyrethrins and Phenobarbital produced an induction of 7-benzyloxy-4-trifluoromethylcoumarin O -debenzylase activity (a CYP1A/2B form marker) and CYP2B1 and CYP2B1/2 mRNA levels. Pyrethrins and Phenobarbital also induced CYP3A-dependent testosterone 6β-hydroxylase activity in rat hepatocytes. In human hepatocytes Pyrethrins and Phenobarbital induced both testosterone 6β-hydroxylase activity and CYP3A4 mRNA levels and also increased CYP2B6 mRNA levels. The effects of Pyrethrins and Phenobarbital were concentration-dependent and exhibited a threshold. These results demonstrate that the effects of Pyrethrins on CYP forms in cultured rat and human hepatocytes are qualitatively similar to those of Phenobarbital. Pyrethrins induce CYP2B and CYP3A forms in cultured rat hepatocytes and can induce CYP3A and CYP2B forms in human hepatocytes. While CYP form induction by Pyrethrins, Phenobarbital and related compounds can be associated with liver and thyroid gland tumour formation in rodents, epidemiological data for Phenobarbital suggests that such effects do not occur in humans.</description><identifier>ISSN: 0300-483X</identifier><identifier>EISSN: 1879-3185</identifier><identifier>DOI: 10.1016/j.tox.2007.09.031</identifier><identifier>PMID: 18022748</identifier><identifier>CODEN: TXICDD</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>Animals ; Biological and medical sciences ; Cells, Cultured ; Cytochrome P-450 Enzyme System - biosynthesis ; Cytochrome P450 ; Dose-Response Relationship, Drug ; Emergency ; Enzyme Induction ; Female ; Hepatocytes - drug effects ; Hepatocytes - enzymology ; Humans ; Insecticides - toxicity ; Medical sciences ; Mode of action ; Pesticides, fertilizers and other agrochemicals toxicology ; Phenobarbital - toxicity ; Pyrethrins ; Pyrethrins - toxicity ; Rat and human hepatocytes ; Rats ; Rats, Sprague-Dawley ; Sodium Phenobarbital ; Species Specificity ; Toxicology</subject><ispartof>Toxicology (Amsterdam), 2008-01, Vol.243 (1), p.84-95</ispartof><rights>2007</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-9d5028dbe9ea9cb0c703b950be3dcb8aba85ae0048eb077ce14af062b7ee12093</citedby><cites>FETCH-LOGICAL-c533t-9d5028dbe9ea9cb0c703b950be3dcb8aba85ae0048eb077ce14af062b7ee12093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.tox.2007.09.031$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19973071$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18022748$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Price, Roger J</creatorcontrib><creatorcontrib>Giddings, Amanda M</creatorcontrib><creatorcontrib>Scott, Mary P</creatorcontrib><creatorcontrib>Walters, David G</creatorcontrib><creatorcontrib>Capen, Charles C</creatorcontrib><creatorcontrib>Osimitz, Thomas G</creatorcontrib><creatorcontrib>Lake, Brian G</creatorcontrib><title>Effect of Pyrethrins on cytochrome P450 forms in cultured rat and human hepatocytes</title><title>Toxicology (Amsterdam)</title><addtitle>Toxicology</addtitle><description>Abstract High doses of Pyrethrins produce liver and thyroid gland tumours in rats by modes of action involving the induction of hepatic xenobiotic metabolising enzymes. The aim of this study was to compare the effects of Pyrethrins with those of the rat liver and thyroid tumour promoter sodium Phenobarbital on some cytochrome P450 (CYP) forms in cultured rat and human hepatocytes. The treatment of female Sprague–Dawley rat and human (both male and female) hepatocytes for 72 h with 0–1000 μM Pyrethrins and 0–1000 μM Phenobarbital did not result in any marked cytotoxicity. In rat hepatocytes both Pyrethrins and Phenobarbital produced an induction of 7-benzyloxy-4-trifluoromethylcoumarin O -debenzylase activity (a CYP1A/2B form marker) and CYP2B1 and CYP2B1/2 mRNA levels. Pyrethrins and Phenobarbital also induced CYP3A-dependent testosterone 6β-hydroxylase activity in rat hepatocytes. In human hepatocytes Pyrethrins and Phenobarbital induced both testosterone 6β-hydroxylase activity and CYP3A4 mRNA levels and also increased CYP2B6 mRNA levels. The effects of Pyrethrins and Phenobarbital were concentration-dependent and exhibited a threshold. These results demonstrate that the effects of Pyrethrins on CYP forms in cultured rat and human hepatocytes are qualitatively similar to those of Phenobarbital. Pyrethrins induce CYP2B and CYP3A forms in cultured rat hepatocytes and can induce CYP3A and CYP2B forms in human hepatocytes. While CYP form induction by Pyrethrins, Phenobarbital and related compounds can be associated with liver and thyroid gland tumour formation in rodents, epidemiological data for Phenobarbital suggests that such effects do not occur in humans.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cells, Cultured</subject><subject>Cytochrome P-450 Enzyme System - biosynthesis</subject><subject>Cytochrome P450</subject><subject>Dose-Response Relationship, Drug</subject><subject>Emergency</subject><subject>Enzyme Induction</subject><subject>Female</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - enzymology</subject><subject>Humans</subject><subject>Insecticides - toxicity</subject><subject>Medical sciences</subject><subject>Mode of action</subject><subject>Pesticides, fertilizers and other agrochemicals toxicology</subject><subject>Phenobarbital - toxicity</subject><subject>Pyrethrins</subject><subject>Pyrethrins - toxicity</subject><subject>Rat and human hepatocytes</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Sodium Phenobarbital</subject><subject>Species Specificity</subject><subject>Toxicology</subject><issn>0300-483X</issn><issn>1879-3185</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcGK1TAUhoMozp3RB3Aj2eiu9aRpmwRBkGEchQEHRsFdSNNTbq5tc01SsW9vyr0w4MJVFuf7_xO-Q8grBiUD1r47lMn_KSsAUYIqgbMnZMekUAVnsnlKdsABilryHxfkMsYDAFS8bp-TCyahqkQtd-ThZhjQJuoHer8GTPvg5kj9TO2avN0HPyG9rxuggw9TpC4PljEtAXsaTKJm7ul-mcxM93g0ObEmjC_Is8GMEV-e3yvy_dPNt-vPxd3X2y_XH-8K23CeCtU3UMm-Q4VG2Q6sAN6pBjrkve2k6YxsDALUEjsQwiKrzQBt1QlEVoHiV-TtqfcY_K8FY9KTixbH0czol6grkEqKdgPZCbTBxxhw0MfgJhNWzUBvJvVBZ5N6M6lB6WwyZ16fy5duwv4xcVaXgTdnwERrxiGY2br4yCklOIit6P2Jw6zit8Ogo3U4W-xdyOZ1791_v_Hhn7Qd3ezywp-4Yjz4JczZsWY6Vhr0w3by7eIgANq8nf8FlQOmaQ</recordid><startdate>20080114</startdate><enddate>20080114</enddate><creator>Price, Roger J</creator><creator>Giddings, Amanda M</creator><creator>Scott, Mary P</creator><creator>Walters, David G</creator><creator>Capen, Charles C</creator><creator>Osimitz, Thomas G</creator><creator>Lake, Brian G</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Science</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></search><sort><creationdate>20080114</creationdate><title>Effect of Pyrethrins on cytochrome P450 forms in cultured rat and human hepatocytes</title><author>Price, Roger J ; Giddings, Amanda M ; Scott, Mary P ; Walters, David G ; Capen, Charles C ; Osimitz, Thomas G ; Lake, Brian G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c533t-9d5028dbe9ea9cb0c703b950be3dcb8aba85ae0048eb077ce14af062b7ee12093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cells, Cultured</topic><topic>Cytochrome P-450 Enzyme System - biosynthesis</topic><topic>Cytochrome P450</topic><topic>Dose-Response Relationship, Drug</topic><topic>Emergency</topic><topic>Enzyme Induction</topic><topic>Female</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - enzymology</topic><topic>Humans</topic><topic>Insecticides - toxicity</topic><topic>Medical sciences</topic><topic>Mode of action</topic><topic>Pesticides, fertilizers and other agrochemicals toxicology</topic><topic>Phenobarbital - toxicity</topic><topic>Pyrethrins</topic><topic>Pyrethrins - toxicity</topic><topic>Rat and human hepatocytes</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Sodium Phenobarbital</topic><topic>Species Specificity</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Price, Roger J</creatorcontrib><creatorcontrib>Giddings, Amanda M</creatorcontrib><creatorcontrib>Scott, Mary P</creatorcontrib><creatorcontrib>Walters, David G</creatorcontrib><creatorcontrib>Capen, Charles C</creatorcontrib><creatorcontrib>Osimitz, Thomas G</creatorcontrib><creatorcontrib>Lake, Brian 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><jtitle>Toxicology (Amsterdam)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Price, Roger J</au><au>Giddings, Amanda M</au><au>Scott, Mary P</au><au>Walters, David G</au><au>Capen, Charles C</au><au>Osimitz, Thomas G</au><au>Lake, Brian G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Pyrethrins on cytochrome P450 forms in cultured rat and human hepatocytes</atitle><jtitle>Toxicology (Amsterdam)</jtitle><addtitle>Toxicology</addtitle><date>2008-01-14</date><risdate>2008</risdate><volume>243</volume><issue>1</issue><spage>84</spage><epage>95</epage><pages>84-95</pages><issn>0300-483X</issn><eissn>1879-3185</eissn><coden>TXICDD</coden><abstract>Abstract High doses of Pyrethrins produce liver and thyroid gland tumours in rats by modes of action involving the induction of hepatic xenobiotic metabolising enzymes. The aim of this study was to compare the effects of Pyrethrins with those of the rat liver and thyroid tumour promoter sodium Phenobarbital on some cytochrome P450 (CYP) forms in cultured rat and human hepatocytes. The treatment of female Sprague–Dawley rat and human (both male and female) hepatocytes for 72 h with 0–1000 μM Pyrethrins and 0–1000 μM Phenobarbital did not result in any marked cytotoxicity. In rat hepatocytes both Pyrethrins and Phenobarbital produced an induction of 7-benzyloxy-4-trifluoromethylcoumarin O -debenzylase activity (a CYP1A/2B form marker) and CYP2B1 and CYP2B1/2 mRNA levels. Pyrethrins and Phenobarbital also induced CYP3A-dependent testosterone 6β-hydroxylase activity in rat hepatocytes. In human hepatocytes Pyrethrins and Phenobarbital induced both testosterone 6β-hydroxylase activity and CYP3A4 mRNA levels and also increased CYP2B6 mRNA levels. The effects of Pyrethrins and Phenobarbital were concentration-dependent and exhibited a threshold. These results demonstrate that the effects of Pyrethrins on CYP forms in cultured rat and human hepatocytes are qualitatively similar to those of Phenobarbital. Pyrethrins induce CYP2B and CYP3A forms in cultured rat hepatocytes and can induce CYP3A and CYP2B forms in human hepatocytes. While CYP form induction by Pyrethrins, Phenobarbital and related compounds can be associated with liver and thyroid gland tumour formation in rodents, epidemiological data for Phenobarbital suggests that such effects do not occur in humans.</abstract><cop>Shannon</cop><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>18022748</pmid><doi>10.1016/j.tox.2007.09.031</doi><tpages>12</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Cells, Cultured Cytochrome P-450 Enzyme System - biosynthesis Cytochrome P450 Dose-Response Relationship, Drug Emergency Enzyme Induction Female Hepatocytes - drug effects Hepatocytes - enzymology Humans Insecticides - toxicity Medical sciences Mode of action Pesticides, fertilizers and other agrochemicals toxicology Phenobarbital - toxicity Pyrethrins Pyrethrins - toxicity Rat and human hepatocytes Rats Rats, Sprague-Dawley Sodium Phenobarbital Species Specificity Toxicology |
| title | Effect of Pyrethrins on cytochrome P450 forms in cultured rat and human hepatocytes |
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