Protein Binding and Metabolism Influence the Relative Skin Sensitization Potential of Cinnamic Compounds
Skin protein modification (haptenation) is thought to be a key step in the manifestation of sensitization to low molecular mass chemicals (
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| Veröffentlicht in: | Chemical research in toxicology 2004-03, Vol.17 (3), p.301-310 |
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| creator | Elahi, Eiram N Wright, Zoe Hinselwood, David Hotchkiss, Sharon A. M Basketter, David A Smith Pease, Camilla K |
| description | Skin protein modification (haptenation) is thought to be a key step in the manifestation of sensitization to low molecular mass chemicals ( |
| doi_str_mv | 10.1021/tx0341456 |
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M ; Basketter, David A ; Smith Pease, Camilla K</creator><creatorcontrib>Elahi, Eiram N ; Wright, Zoe ; Hinselwood, David ; Hotchkiss, Sharon A. M ; Basketter, David A ; Smith Pease, Camilla K</creatorcontrib><description>Skin protein modification (haptenation) is thought to be a key step in the manifestation of sensitization to low molecular mass chemicals (<500 g/mol). For sensitizing chemicals that are not protein reactive, it is hypothesised that metabolic activation can convert such chemicals into protein reactive toxins within the skin. trans-Cinnamaldehyde, α-amyl cinnamaldehyde, and trans-cinnamic alcohol are known sensitizers with differing potencies in man, where the former two are protein reactive and the latter is not. Here, we have used immunochemical methods to investigate the extent of protein−cinnamaldehyde binding in rat and human skin homogenates that have been incubated (for either 5, 15, 30, or 60 min) at 37 °C with cinnamaldehyde, α-amyl cinnamaldehyde (at concentrations of between 1 and 40 mM), and cinnamic alcohol (at higher concentrations of 200 or 400 mM). Cinnamaldehyde specific antiserum was raised specially. A broad range (in terms of molecular mass) of protein−cinnamaldehyde adducts was detected (as formed in a time- and concentration-dependent manner) in skin treated with cinnamaldehyde and cinnamic alcohol but not with α-amyl cinnamaldehyde. Mechanistic observations have been related to relative skin sensitization potential, as determined using the local lymph node assay (LLNA) as a biological read-out. The work presented here suggests that there is a common hapten involved in cinnamaldehyde and cinnamic alcohol sensitization and that metabolic activation (to cinnamaldehyde) is involved in the latter. Conversely, there does not appear to be a common hapten for cinnamaldehyde and α-amyl cinnamaldehyde. Such mechanistic work on protein modification is important in understanding the early mechanisms of skin sensitization. Such knowledge can then be used in order that effective and appropriate in vitro/in silico tools for predicting sensitization potential, with a high confidence, can be developed.</description><identifier>ISSN: 0893-228X</identifier><identifier>EISSN: 1520-5010</identifier><identifier>DOI: 10.1021/tx0341456</identifier><identifier>PMID: 15025500</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Acrolein - analogs & derivatives ; Acrolein - pharmacokinetics ; Acrolein - toxicity ; Aldehydes - pharmacokinetics ; Aldehydes - toxicity ; Animals ; Dermatitis, Contact - etiology ; Dermatitis, Contact - metabolism ; Dermatitis, Contact - pathology ; Dose-Response Relationship, Drug ; Female ; Humans ; Immunoenzyme Techniques ; Local Lymph Node Assay ; Propanols - pharmacokinetics ; Propanols - toxicity ; Protein Binding ; Rabbits ; Rats ; Rats, Inbred F344 ; Skin - drug effects ; Skin - metabolism ; Skin - pathology</subject><ispartof>Chemical research in toxicology, 2004-03, Vol.17 (3), p.301-310</ispartof><rights>Copyright © 2004 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a446t-f3e80ad3fb234712b37bc34854b8aea71438c17de3c8cf8b9f76121dfd2de5db3</citedby><cites>FETCH-LOGICAL-a446t-f3e80ad3fb234712b37bc34854b8aea71438c17de3c8cf8b9f76121dfd2de5db3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/tx0341456$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/tx0341456$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>315,782,786,2767,27083,27931,27932,56745,56795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15025500$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Elahi, Eiram N</creatorcontrib><creatorcontrib>Wright, Zoe</creatorcontrib><creatorcontrib>Hinselwood, David</creatorcontrib><creatorcontrib>Hotchkiss, Sharon A. M</creatorcontrib><creatorcontrib>Basketter, David A</creatorcontrib><creatorcontrib>Smith Pease, Camilla K</creatorcontrib><title>Protein Binding and Metabolism Influence the Relative Skin Sensitization Potential of Cinnamic Compounds</title><title>Chemical research in toxicology</title><addtitle>Chem. Res. Toxicol</addtitle><description>Skin protein modification (haptenation) is thought to be a key step in the manifestation of sensitization to low molecular mass chemicals (<500 g/mol). For sensitizing chemicals that are not protein reactive, it is hypothesised that metabolic activation can convert such chemicals into protein reactive toxins within the skin. trans-Cinnamaldehyde, α-amyl cinnamaldehyde, and trans-cinnamic alcohol are known sensitizers with differing potencies in man, where the former two are protein reactive and the latter is not. Here, we have used immunochemical methods to investigate the extent of protein−cinnamaldehyde binding in rat and human skin homogenates that have been incubated (for either 5, 15, 30, or 60 min) at 37 °C with cinnamaldehyde, α-amyl cinnamaldehyde (at concentrations of between 1 and 40 mM), and cinnamic alcohol (at higher concentrations of 200 or 400 mM). Cinnamaldehyde specific antiserum was raised specially. A broad range (in terms of molecular mass) of protein−cinnamaldehyde adducts was detected (as formed in a time- and concentration-dependent manner) in skin treated with cinnamaldehyde and cinnamic alcohol but not with α-amyl cinnamaldehyde. Mechanistic observations have been related to relative skin sensitization potential, as determined using the local lymph node assay (LLNA) as a biological read-out. The work presented here suggests that there is a common hapten involved in cinnamaldehyde and cinnamic alcohol sensitization and that metabolic activation (to cinnamaldehyde) is involved in the latter. Conversely, there does not appear to be a common hapten for cinnamaldehyde and α-amyl cinnamaldehyde. Such mechanistic work on protein modification is important in understanding the early mechanisms of skin sensitization. Such knowledge can then be used in order that effective and appropriate in vitro/in silico tools for predicting sensitization potential, with a high confidence, can be developed.</description><subject>Acrolein - analogs & derivatives</subject><subject>Acrolein - pharmacokinetics</subject><subject>Acrolein - toxicity</subject><subject>Aldehydes - pharmacokinetics</subject><subject>Aldehydes - toxicity</subject><subject>Animals</subject><subject>Dermatitis, Contact - etiology</subject><subject>Dermatitis, Contact - metabolism</subject><subject>Dermatitis, Contact - pathology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Local Lymph Node Assay</subject><subject>Propanols - pharmacokinetics</subject><subject>Propanols - toxicity</subject><subject>Protein Binding</subject><subject>Rabbits</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Skin - drug effects</subject><subject>Skin - metabolism</subject><subject>Skin - pathology</subject><issn>0893-228X</issn><issn>1520-5010</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0Mtu1DAUBmALgei0sOAFKm-o1EXAlzjOLNsRvaBBDExB7CzHPm7dJvYQO6jl6Ws0o3bDytLxd_4j_Qi9o-QDJYx-zPeE17QWzQs0o4KRShBKXqIZaee8Yqz9tYf2U7olhBYuX6M9KggTgpAZulmNMYMP-NQH68M11sHiL5B1F3ufBnwZXD9BMIDzDeDv0Ovs_wBe35WVNYTks_9bRjHgVckJ2eseR4cXPgQ9eIMXcdjEKdj0Br1yuk_wdvceoB9nn64WF9Xy6_nl4mRZ6bpucuU4tERb7jrGa0lZx2VneN2Kums1aElr3hoqLXDTGtd2cycbyqh1llkQtuMH6Gibuxnj7wlSVoNPBvpeB4hTUlTOGW0EK_B4C80YUxrBqc3oBz0-KErUv1rVU63FHu5Cp24A-yx3PRZQbYFPGe6f_vV4pxrJpVBXq7U6-7z8KU6_cbUq_v3Wa5PUbZzGUDr5z-FHW1-O9g</recordid><startdate>20040301</startdate><enddate>20040301</enddate><creator>Elahi, Eiram N</creator><creator>Wright, Zoe</creator><creator>Hinselwood, David</creator><creator>Hotchkiss, Sharon A. M</creator><creator>Basketter, David A</creator><creator>Smith Pease, Camilla K</creator><general>American Chemical Society</general><scope>BSCLL</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>20040301</creationdate><title>Protein Binding and Metabolism Influence the Relative Skin Sensitization Potential of Cinnamic Compounds</title><author>Elahi, Eiram N ; Wright, Zoe ; Hinselwood, David ; Hotchkiss, Sharon A. M ; Basketter, David A ; Smith Pease, Camilla K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a446t-f3e80ad3fb234712b37bc34854b8aea71438c17de3c8cf8b9f76121dfd2de5db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Acrolein - analogs & derivatives</topic><topic>Acrolein - pharmacokinetics</topic><topic>Acrolein - toxicity</topic><topic>Aldehydes - pharmacokinetics</topic><topic>Aldehydes - toxicity</topic><topic>Animals</topic><topic>Dermatitis, Contact - etiology</topic><topic>Dermatitis, Contact - metabolism</topic><topic>Dermatitis, Contact - pathology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Local Lymph Node Assay</topic><topic>Propanols - pharmacokinetics</topic><topic>Propanols - toxicity</topic><topic>Protein Binding</topic><topic>Rabbits</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Skin - drug effects</topic><topic>Skin - metabolism</topic><topic>Skin - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Elahi, Eiram N</creatorcontrib><creatorcontrib>Wright, Zoe</creatorcontrib><creatorcontrib>Hinselwood, David</creatorcontrib><creatorcontrib>Hotchkiss, Sharon A. M</creatorcontrib><creatorcontrib>Basketter, David A</creatorcontrib><creatorcontrib>Smith Pease, Camilla K</creatorcontrib><collection>Istex</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>Chemical research in toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Elahi, Eiram N</au><au>Wright, Zoe</au><au>Hinselwood, David</au><au>Hotchkiss, Sharon A. M</au><au>Basketter, David A</au><au>Smith Pease, Camilla K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protein Binding and Metabolism Influence the Relative Skin Sensitization Potential of Cinnamic Compounds</atitle><jtitle>Chemical research in toxicology</jtitle><addtitle>Chem. Res. Toxicol</addtitle><date>2004-03-01</date><risdate>2004</risdate><volume>17</volume><issue>3</issue><spage>301</spage><epage>310</epage><pages>301-310</pages><issn>0893-228X</issn><eissn>1520-5010</eissn><abstract>Skin protein modification (haptenation) is thought to be a key step in the manifestation of sensitization to low molecular mass chemicals (<500 g/mol). For sensitizing chemicals that are not protein reactive, it is hypothesised that metabolic activation can convert such chemicals into protein reactive toxins within the skin. trans-Cinnamaldehyde, α-amyl cinnamaldehyde, and trans-cinnamic alcohol are known sensitizers with differing potencies in man, where the former two are protein reactive and the latter is not. Here, we have used immunochemical methods to investigate the extent of protein−cinnamaldehyde binding in rat and human skin homogenates that have been incubated (for either 5, 15, 30, or 60 min) at 37 °C with cinnamaldehyde, α-amyl cinnamaldehyde (at concentrations of between 1 and 40 mM), and cinnamic alcohol (at higher concentrations of 200 or 400 mM). Cinnamaldehyde specific antiserum was raised specially. A broad range (in terms of molecular mass) of protein−cinnamaldehyde adducts was detected (as formed in a time- and concentration-dependent manner) in skin treated with cinnamaldehyde and cinnamic alcohol but not with α-amyl cinnamaldehyde. Mechanistic observations have been related to relative skin sensitization potential, as determined using the local lymph node assay (LLNA) as a biological read-out. The work presented here suggests that there is a common hapten involved in cinnamaldehyde and cinnamic alcohol sensitization and that metabolic activation (to cinnamaldehyde) is involved in the latter. Conversely, there does not appear to be a common hapten for cinnamaldehyde and α-amyl cinnamaldehyde. Such mechanistic work on protein modification is important in understanding the early mechanisms of skin sensitization. Such knowledge can then be used in order that effective and appropriate in vitro/in silico tools for predicting sensitization potential, with a high confidence, can be developed.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>15025500</pmid><doi>10.1021/tx0341456</doi><tpages>10</tpages></addata></record> |
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| subjects | Acrolein - analogs & derivatives Acrolein - pharmacokinetics Acrolein - toxicity Aldehydes - pharmacokinetics Aldehydes - toxicity Animals Dermatitis, Contact - etiology Dermatitis, Contact - metabolism Dermatitis, Contact - pathology Dose-Response Relationship, Drug Female Humans Immunoenzyme Techniques Local Lymph Node Assay Propanols - pharmacokinetics Propanols - toxicity Protein Binding Rabbits Rats Rats, Inbred F344 Skin - drug effects Skin - metabolism Skin - pathology |
| title | Protein Binding and Metabolism Influence the Relative Skin Sensitization Potential of Cinnamic Compounds |
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