Black pepper constituent piperine: Genotoxicity studies in vitro and in vivo
•Piperine was negative in an in vivo MNT in bone marrow cells up to the MTD.•Piperine is not genotoxic in CHO cells.•The hypothermic and hematotoxic effects of piperine did not results in increased micronuclei frequencies in the in vivo MNT. Piperine is responsible for the hot taste of black pepper....
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Veröffentlicht in: | Food and chemical toxicology 2014-04, Vol.66, p.350-357 |
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description | •Piperine was negative in an in vivo MNT in bone marrow cells up to the MTD.•Piperine is not genotoxic in CHO cells.•The hypothermic and hematotoxic effects of piperine did not results in increased micronuclei frequencies in the in vivo MNT.
Piperine is responsible for the hot taste of black pepper. Publications on genotoxicity of piperine are reported: negative Ames Tests and one in vitro micronucleus test (MNT). In vivo tests were mainly negative. In the majority of the data the administered dose levels did not follow the dose selection requirements of regulatory guidelines of having dose levels up to the maximum tolerated dose (MTD). The only oral high dose studies were a positive in vivo MNT in mice in contrast to a negative in vivo chromosome aberration test in rats. Thus, conflicting results in genotoxicity testing are published.
To investigate this further, we administered piperine to mice up to the MTD and determined micronuclei-frequency. Piperine reduces core body temperature and interferes with blood cells both being known to result in irrelevant positive in vivo MNTs. Therefore we added mechanistic endpoints: core body temperature, haematology, erythropoietin level, and organ weights. Additionally an in vitro MNT in Chinese hamster ovary cells was performed.
Piperine was negative in the in vitro MNT. It caused significant reduction of core body temperature, decrease of white blood cells and spleen weights but no increase in the micronucleus-frequency. Thus, in our studies piperine was not genotoxic. |
doi_str_mv | 10.1016/j.fct.2014.01.056 |
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Piperine is responsible for the hot taste of black pepper. Publications on genotoxicity of piperine are reported: negative Ames Tests and one in vitro micronucleus test (MNT). In vivo tests were mainly negative. In the majority of the data the administered dose levels did not follow the dose selection requirements of regulatory guidelines of having dose levels up to the maximum tolerated dose (MTD). The only oral high dose studies were a positive in vivo MNT in mice in contrast to a negative in vivo chromosome aberration test in rats. Thus, conflicting results in genotoxicity testing are published.
To investigate this further, we administered piperine to mice up to the MTD and determined micronuclei-frequency. Piperine reduces core body temperature and interferes with blood cells both being known to result in irrelevant positive in vivo MNTs. Therefore we added mechanistic endpoints: core body temperature, haematology, erythropoietin level, and organ weights. Additionally an in vitro MNT in Chinese hamster ovary cells was performed.
Piperine was negative in the in vitro MNT. It caused significant reduction of core body temperature, decrease of white blood cells and spleen weights but no increase in the micronucleus-frequency. Thus, in our studies piperine was not genotoxic.</description><identifier>ISSN: 0278-6915</identifier><identifier>EISSN: 1873-6351</identifier><identifier>DOI: 10.1016/j.fct.2014.01.056</identifier><identifier>PMID: 24525095</identifier><identifier>CODEN: FCTOD7</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Alkaloids - toxicity ; Animals ; Benzodioxoles - toxicity ; Biological and medical sciences ; Black pepper ; CHO Cells ; Cricetinae ; Cricetulus ; Female ; Food toxicology ; Genotoxicity ; In Vitro Techniques ; Male ; Medical sciences ; Mice ; Micronucleus ; Mutagenicity Tests ; Piper nigrum ; Piper nigrum - chemistry ; Piperidines - toxicity ; Piperine ; Polyunsaturated Alkamides - toxicity ; Toxicology</subject><ispartof>Food and chemical toxicology, 2014-04, Vol.66, p.350-357</ispartof><rights>2014 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2014 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-64480490351f3351a9d73af02b06ec8cb992725c9b9319bdc5c19145a1c4ebb83</citedby><cites>FETCH-LOGICAL-c416t-64480490351f3351a9d73af02b06ec8cb992725c9b9319bdc5c19145a1c4ebb83</cites><orcidid>0000-0002-3748-0621</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.fct.2014.01.056$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28392659$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24525095$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thiel, Anette</creatorcontrib><creatorcontrib>Buskens, Carin</creatorcontrib><creatorcontrib>Woehrle, Tina</creatorcontrib><creatorcontrib>Etheve, Stéphane</creatorcontrib><creatorcontrib>Schoenmakers, Ankie</creatorcontrib><creatorcontrib>Fehr, Markus</creatorcontrib><creatorcontrib>Beilstein, Paul</creatorcontrib><title>Black pepper constituent piperine: Genotoxicity studies in vitro and in vivo</title><title>Food and chemical toxicology</title><addtitle>Food Chem Toxicol</addtitle><description>•Piperine was negative in an in vivo MNT in bone marrow cells up to the MTD.•Piperine is not genotoxic in CHO cells.•The hypothermic and hematotoxic effects of piperine did not results in increased micronuclei frequencies in the in vivo MNT.
Piperine is responsible for the hot taste of black pepper. Publications on genotoxicity of piperine are reported: negative Ames Tests and one in vitro micronucleus test (MNT). In vivo tests were mainly negative. In the majority of the data the administered dose levels did not follow the dose selection requirements of regulatory guidelines of having dose levels up to the maximum tolerated dose (MTD). The only oral high dose studies were a positive in vivo MNT in mice in contrast to a negative in vivo chromosome aberration test in rats. Thus, conflicting results in genotoxicity testing are published.
To investigate this further, we administered piperine to mice up to the MTD and determined micronuclei-frequency. Piperine reduces core body temperature and interferes with blood cells both being known to result in irrelevant positive in vivo MNTs. Therefore we added mechanistic endpoints: core body temperature, haematology, erythropoietin level, and organ weights. Additionally an in vitro MNT in Chinese hamster ovary cells was performed.
Piperine was negative in the in vitro MNT. It caused significant reduction of core body temperature, decrease of white blood cells and spleen weights but no increase in the micronucleus-frequency. Thus, in our studies piperine was not genotoxic.</description><subject>Alkaloids - toxicity</subject><subject>Animals</subject><subject>Benzodioxoles - toxicity</subject><subject>Biological and medical sciences</subject><subject>Black pepper</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Female</subject><subject>Food toxicology</subject><subject>Genotoxicity</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Micronucleus</subject><subject>Mutagenicity Tests</subject><subject>Piper nigrum</subject><subject>Piper nigrum - chemistry</subject><subject>Piperidines - toxicity</subject><subject>Piperine</subject><subject>Polyunsaturated Alkamides - toxicity</subject><subject>Toxicology</subject><issn>0278-6915</issn><issn>1873-6351</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kDuP1DAQgC0E4paDH0CD0iDRJHjiVwzVcYIDaSUaqC3HmUhesnawnRX37_FpF-hoZjSjbx76CHkJtAMK8u2hm13pegq8o9BRIR-RHQyKtZIJeEx2tFdDKzWIK_Is5wOlVIGST8lVz0UvqBY7sv-wWPejWXFdMTUuhlx82TCUZvW14wO-a-4wxBJ_eefLfZPLNnnMjQ_NyZcUGxumc3GKz8mT2S4ZX1zyNfn-6eO328_t_uvdl9ubfes4yNJKzgfKNa1PzqwGqyfF7Ez7kUp0gxu17lUvnB41Az1OTjjQwIUFx3EcB3ZN3pz3rin-3DAXc_TZ4bLYgHHLBqSSjCtgqqJwRl2KOSeczZr80aZ7A9Q8SDQHUyWaB4mGgqkS68yry_ptPOL0d-KPtQq8vgA2O7vMyQbn8z9uYLqXQlfu_ZnDKuPkMZnsPAaHk09Yj07R_-eN33-Ajno</recordid><startdate>20140401</startdate><enddate>20140401</enddate><creator>Thiel, Anette</creator><creator>Buskens, Carin</creator><creator>Woehrle, Tina</creator><creator>Etheve, Stéphane</creator><creator>Schoenmakers, Ankie</creator><creator>Fehr, Markus</creator><creator>Beilstein, Paul</creator><general>Elsevier Ltd</general><general>Elsevier</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><orcidid>https://orcid.org/0000-0002-3748-0621</orcidid></search><sort><creationdate>20140401</creationdate><title>Black pepper constituent piperine: Genotoxicity studies in vitro and in vivo</title><author>Thiel, Anette ; Buskens, Carin ; Woehrle, Tina ; Etheve, Stéphane ; Schoenmakers, Ankie ; Fehr, Markus ; Beilstein, Paul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-64480490351f3351a9d73af02b06ec8cb992725c9b9319bdc5c19145a1c4ebb83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Alkaloids - toxicity</topic><topic>Animals</topic><topic>Benzodioxoles - toxicity</topic><topic>Biological and medical sciences</topic><topic>Black pepper</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>Female</topic><topic>Food toxicology</topic><topic>Genotoxicity</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Micronucleus</topic><topic>Mutagenicity Tests</topic><topic>Piper nigrum</topic><topic>Piper nigrum - chemistry</topic><topic>Piperidines - toxicity</topic><topic>Piperine</topic><topic>Polyunsaturated Alkamides - toxicity</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thiel, Anette</creatorcontrib><creatorcontrib>Buskens, Carin</creatorcontrib><creatorcontrib>Woehrle, Tina</creatorcontrib><creatorcontrib>Etheve, Stéphane</creatorcontrib><creatorcontrib>Schoenmakers, Ankie</creatorcontrib><creatorcontrib>Fehr, Markus</creatorcontrib><creatorcontrib>Beilstein, Paul</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>Food and chemical toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thiel, Anette</au><au>Buskens, Carin</au><au>Woehrle, Tina</au><au>Etheve, Stéphane</au><au>Schoenmakers, Ankie</au><au>Fehr, Markus</au><au>Beilstein, Paul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Black pepper constituent piperine: Genotoxicity studies in vitro and in vivo</atitle><jtitle>Food and chemical toxicology</jtitle><addtitle>Food Chem Toxicol</addtitle><date>2014-04-01</date><risdate>2014</risdate><volume>66</volume><spage>350</spage><epage>357</epage><pages>350-357</pages><issn>0278-6915</issn><eissn>1873-6351</eissn><coden>FCTOD7</coden><abstract>•Piperine was negative in an in vivo MNT in bone marrow cells up to the MTD.•Piperine is not genotoxic in CHO cells.•The hypothermic and hematotoxic effects of piperine did not results in increased micronuclei frequencies in the in vivo MNT.
Piperine is responsible for the hot taste of black pepper. Publications on genotoxicity of piperine are reported: negative Ames Tests and one in vitro micronucleus test (MNT). In vivo tests were mainly negative. In the majority of the data the administered dose levels did not follow the dose selection requirements of regulatory guidelines of having dose levels up to the maximum tolerated dose (MTD). The only oral high dose studies were a positive in vivo MNT in mice in contrast to a negative in vivo chromosome aberration test in rats. Thus, conflicting results in genotoxicity testing are published.
To investigate this further, we administered piperine to mice up to the MTD and determined micronuclei-frequency. Piperine reduces core body temperature and interferes with blood cells both being known to result in irrelevant positive in vivo MNTs. Therefore we added mechanistic endpoints: core body temperature, haematology, erythropoietin level, and organ weights. Additionally an in vitro MNT in Chinese hamster ovary cells was performed.
Piperine was negative in the in vitro MNT. It caused significant reduction of core body temperature, decrease of white blood cells and spleen weights but no increase in the micronucleus-frequency. Thus, in our studies piperine was not genotoxic.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>24525095</pmid><doi>10.1016/j.fct.2014.01.056</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-3748-0621</orcidid></addata></record> |
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subjects | Alkaloids - toxicity Animals Benzodioxoles - toxicity Biological and medical sciences Black pepper CHO Cells Cricetinae Cricetulus Female Food toxicology Genotoxicity In Vitro Techniques Male Medical sciences Mice Micronucleus Mutagenicity Tests Piper nigrum Piper nigrum - chemistry Piperidines - toxicity Piperine Polyunsaturated Alkamides - toxicity Toxicology |
title | Black pepper constituent piperine: Genotoxicity studies in vitro and in vivo |
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