Protection against 2-chloroethyl ethyl sulfide (CEES) — induced cytotoxicity in human keratinocytes by an inducer of the glutathione detoxification pathway
Sulfur mustard (SM or mustard gas) was first used as a chemical warfare agent almost 100years ago. Due to its toxic effects on the eyes, lungs, and skin, and the relative ease with which it may be synthesized, mustard gas remains a potential chemical threat to the present day. SM exposed skin develo...
Gespeichert in:
| Veröffentlicht in: | Toxicology and applied pharmacology 2011-09, Vol.255 (2), p.176-183 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 183 |
|---|---|
| container_issue | 2 |
| container_start_page | 176 |
| container_title | Toxicology and applied pharmacology |
| container_volume | 255 |
| creator | Abel, Erika L. Bubel, Jennifer D. Simper, Melissa S. Powell, Leslie McClellan, S. Alex Andreeff, Michael MacLeod, Michael C. DiGiovanni, John |
| description | Sulfur mustard (SM or mustard gas) was first used as a chemical warfare agent almost 100years ago. Due to its toxic effects on the eyes, lungs, and skin, and the relative ease with which it may be synthesized, mustard gas remains a potential chemical threat to the present day. SM exposed skin develops fluid filled bullae resulting from potent cytotoxicity of cells lining the basement membrane of the epidermis. Currently, there are no antidotes for SM exposure; therefore, chemopreventive measures for first responders following an SM attack are needed. Glutathione (GSH) is known to have a protective effect against SM toxicity, and detoxification of SM is believed to occur, in part, via GSH conjugation. Therefore, we screened 6 potential chemopreventive agents for ability to induce GSH synthesis and protect cultured human keratinocytes against the SM analog, 2-chloroethyl ethyl sulfide (CEES). Using NCTC2544 human keratinocytes, we found that both sulforaphane and methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) stimulated nuclear localization of Nrf2 and induced expression of the GSH synthesis gene, GCLM. Additionally, we found that treatment with CDDO-Me elevated reduced GSH content of NCTC2544 cells and preserved their viability by ~3-fold following exposure to CEES. Our data also suggested that CDDO-Me may act additively with 2,6-dithiopurine (DTP), a nucleophilic scavenging agent, to increase the viability of keratinocytes exposed to CEES. These results suggest that CDDO-Me is a promising chemopreventive agent for SM toxicity in the skin.
► CDDO-Me treatment increased intracellular GSH in human keratinocytes. ► CDDO-Me increased cell viability following exposure to the half-mustard, CEES. ► The cytoprotective effect of CDDO-Me was likely due to scavenging with endogenous GSH. |
| doi_str_mv | 10.1016/j.taap.2011.06.012 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_osti_</sourceid><recordid>TN_cdi_osti_scitechconnect_21587827</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0041008X11002341</els_id><sourcerecordid>888110492</sourcerecordid><originalsourceid>FETCH-LOGICAL-c445t-545cd7643937fe9b33dd3f94f13b3459d928cc70c20e17625ecab192b598a30c3</originalsourceid><addsrcrecordid>eNp9kcuO1DAQRSMEYnoGfoAFsoTQwCKh_MhLYoNazUMaCSRAYmc5TmXiJh03tgNkx0ew5ef4EhzSwI6NLV2fuq6qmyT3KGQUaPFknwWljhkDSjMoMqDsRrKhUBcpcM5vJhsAQVOA6sNZcu79HgBqIejt5IzRknEOxSb58cbZgDoYOxJ1rczoA2Gp7gfrLIZ-Hsh6-mnoTIvk0Xa3e_uY_Pz2nZixnTS2RM_BBvvVaBPmKJJ-OqiRfESnghltfEVPmplEba1wxHYk9Eiuhymo0MevkbS4WHRGq9-tHKP-Rc13kludGjzePd0Xyfvnu3fbl-nV6xevts-uUi1EHtJc5LotC8FrXnZYN5y3Le9q0VHecJHXbc0qrUvQDJCWBctRq4bWrMnrSnHQ_CJ5sPpaH4z0cRLUvbbjGDcjGc2rsmJlpC5X6ujspwl9kAfjNQ6DGtFOXlZVRSmImkWSraR21nuHnTw6c1BulhTkkp3cyyU7uWQnoZAxu1h0_2Q_NQds_5b8CSsCD0-A8loNnVOjNv4fJ0QFoqKRe7pyGFf22aBbJsIxZmXcMlBrzf_6-AVxirqa</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>888110492</pqid></control><display><type>article</type><title>Protection against 2-chloroethyl ethyl sulfide (CEES) — induced cytotoxicity in human keratinocytes by an inducer of the glutathione detoxification pathway</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Abel, Erika L. ; Bubel, Jennifer D. ; Simper, Melissa S. ; Powell, Leslie ; McClellan, S. Alex ; Andreeff, Michael ; MacLeod, Michael C. ; DiGiovanni, John</creator><creatorcontrib>Abel, Erika L. ; Bubel, Jennifer D. ; Simper, Melissa S. ; Powell, Leslie ; McClellan, S. Alex ; Andreeff, Michael ; MacLeod, Michael C. ; DiGiovanni, John</creatorcontrib><description>Sulfur mustard (SM or mustard gas) was first used as a chemical warfare agent almost 100years ago. Due to its toxic effects on the eyes, lungs, and skin, and the relative ease with which it may be synthesized, mustard gas remains a potential chemical threat to the present day. SM exposed skin develops fluid filled bullae resulting from potent cytotoxicity of cells lining the basement membrane of the epidermis. Currently, there are no antidotes for SM exposure; therefore, chemopreventive measures for first responders following an SM attack are needed. Glutathione (GSH) is known to have a protective effect against SM toxicity, and detoxification of SM is believed to occur, in part, via GSH conjugation. Therefore, we screened 6 potential chemopreventive agents for ability to induce GSH synthesis and protect cultured human keratinocytes against the SM analog, 2-chloroethyl ethyl sulfide (CEES). Using NCTC2544 human keratinocytes, we found that both sulforaphane and methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) stimulated nuclear localization of Nrf2 and induced expression of the GSH synthesis gene, GCLM. Additionally, we found that treatment with CDDO-Me elevated reduced GSH content of NCTC2544 cells and preserved their viability by ~3-fold following exposure to CEES. Our data also suggested that CDDO-Me may act additively with 2,6-dithiopurine (DTP), a nucleophilic scavenging agent, to increase the viability of keratinocytes exposed to CEES. These results suggest that CDDO-Me is a promising chemopreventive agent for SM toxicity in the skin.
► CDDO-Me treatment increased intracellular GSH in human keratinocytes. ► CDDO-Me increased cell viability following exposure to the half-mustard, CEES. ► The cytoprotective effect of CDDO-Me was likely due to scavenging with endogenous GSH.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2011.06.012</identifier><identifier>PMID: 21723306</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; AMINO ACIDS ; ANIMAL TISSUES ; AROMATICS ; Biological and medical sciences ; Blotting, Western ; BODY ; BRASSICA ; CARBOXYLIC ACIDS ; CDDO-Me ; Cell Line ; Cell Survival - drug effects ; CHALCOGENIDES ; CHELATING AGENTS ; Chemical and industrial products toxicology. Toxic occupational diseases ; CHEMICAL WARFARE AGENTS ; Chemical Warfare Agents - pharmacokinetics ; Chemical Warfare Agents - toxicity ; CONDENSED AROMATICS ; CYSTEINE ; Cytotoxicity ; DETOXIFICATION ; DMSO ; Drug Interactions ; DRUGS ; EDTA ; ENZYMES ; EPIDERMIS ; Epidermis - cytology ; Epidermis - drug effects ; Epidermis - metabolism ; EPITHELIUM ; FOOD ; Gas, fumes ; GLUTATHIONE ; Glutathione - metabolism ; Humans ; HYDROCARBONS ; Inactivation, Metabolic ; Keratinocytes ; Keratinocytes - drug effects ; Keratinocytes - metabolism ; LIGASES ; LUNGS ; MAGNOLIOPHYTA ; MAGNOLIOPSIDA ; Medical sciences ; Mustard Gas - analogs & derivatives ; Mustard Gas - pharmacokinetics ; Mustard Gas - toxicity ; NAPHTHALENE ; NF-E2-Related Factor 2 - metabolism ; Oleanolic Acid - analogs & derivatives ; Oleanolic Acid - pharmacology ; ORGANIC ACIDS ; ORGANIC COMPOUNDS ; ORGANIC SULFUR COMPOUNDS ; ORGANS ; PEPTIDES ; PLANTS ; POLYPEPTIDES ; PROTEINS ; RADIOPROTECTIVE SUBSTANCES ; RESPIRATORY SYSTEM ; RESPONSE MODIFYING FACTORS ; SKIN ; SULFIDES ; SULFOXIDES ; SULFUR COMPOUNDS ; Sulfur mustard ; SYNTHESIS ; THIOLS ; TOXICITY ; Toxicology ; VEGETABLES ; VIABILITY ; WEAPONS</subject><ispartof>Toxicology and applied pharmacology, 2011-09, Vol.255 (2), p.176-183</ispartof><rights>2011</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-545cd7643937fe9b33dd3f94f13b3459d928cc70c20e17625ecab192b598a30c3</citedby><cites>FETCH-LOGICAL-c445t-545cd7643937fe9b33dd3f94f13b3459d928cc70c20e17625ecab192b598a30c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.taap.2011.06.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24480481$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21723306$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/21587827$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Abel, Erika L.</creatorcontrib><creatorcontrib>Bubel, Jennifer D.</creatorcontrib><creatorcontrib>Simper, Melissa S.</creatorcontrib><creatorcontrib>Powell, Leslie</creatorcontrib><creatorcontrib>McClellan, S. Alex</creatorcontrib><creatorcontrib>Andreeff, Michael</creatorcontrib><creatorcontrib>MacLeod, Michael C.</creatorcontrib><creatorcontrib>DiGiovanni, John</creatorcontrib><title>Protection against 2-chloroethyl ethyl sulfide (CEES) — induced cytotoxicity in human keratinocytes by an inducer of the glutathione detoxification pathway</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>Sulfur mustard (SM or mustard gas) was first used as a chemical warfare agent almost 100years ago. Due to its toxic effects on the eyes, lungs, and skin, and the relative ease with which it may be synthesized, mustard gas remains a potential chemical threat to the present day. SM exposed skin develops fluid filled bullae resulting from potent cytotoxicity of cells lining the basement membrane of the epidermis. Currently, there are no antidotes for SM exposure; therefore, chemopreventive measures for first responders following an SM attack are needed. Glutathione (GSH) is known to have a protective effect against SM toxicity, and detoxification of SM is believed to occur, in part, via GSH conjugation. Therefore, we screened 6 potential chemopreventive agents for ability to induce GSH synthesis and protect cultured human keratinocytes against the SM analog, 2-chloroethyl ethyl sulfide (CEES). Using NCTC2544 human keratinocytes, we found that both sulforaphane and methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) stimulated nuclear localization of Nrf2 and induced expression of the GSH synthesis gene, GCLM. Additionally, we found that treatment with CDDO-Me elevated reduced GSH content of NCTC2544 cells and preserved their viability by ~3-fold following exposure to CEES. Our data also suggested that CDDO-Me may act additively with 2,6-dithiopurine (DTP), a nucleophilic scavenging agent, to increase the viability of keratinocytes exposed to CEES. These results suggest that CDDO-Me is a promising chemopreventive agent for SM toxicity in the skin.
► CDDO-Me treatment increased intracellular GSH in human keratinocytes. ► CDDO-Me increased cell viability following exposure to the half-mustard, CEES. ► The cytoprotective effect of CDDO-Me was likely due to scavenging with endogenous GSH.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>AMINO ACIDS</subject><subject>ANIMAL TISSUES</subject><subject>AROMATICS</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>BODY</subject><subject>BRASSICA</subject><subject>CARBOXYLIC ACIDS</subject><subject>CDDO-Me</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>CHALCOGENIDES</subject><subject>CHELATING AGENTS</subject><subject>Chemical and industrial products toxicology. Toxic occupational diseases</subject><subject>CHEMICAL WARFARE AGENTS</subject><subject>Chemical Warfare Agents - pharmacokinetics</subject><subject>Chemical Warfare Agents - toxicity</subject><subject>CONDENSED AROMATICS</subject><subject>CYSTEINE</subject><subject>Cytotoxicity</subject><subject>DETOXIFICATION</subject><subject>DMSO</subject><subject>Drug Interactions</subject><subject>DRUGS</subject><subject>EDTA</subject><subject>ENZYMES</subject><subject>EPIDERMIS</subject><subject>Epidermis - cytology</subject><subject>Epidermis - drug effects</subject><subject>Epidermis - metabolism</subject><subject>EPITHELIUM</subject><subject>FOOD</subject><subject>Gas, fumes</subject><subject>GLUTATHIONE</subject><subject>Glutathione - metabolism</subject><subject>Humans</subject><subject>HYDROCARBONS</subject><subject>Inactivation, Metabolic</subject><subject>Keratinocytes</subject><subject>Keratinocytes - drug effects</subject><subject>Keratinocytes - metabolism</subject><subject>LIGASES</subject><subject>LUNGS</subject><subject>MAGNOLIOPHYTA</subject><subject>MAGNOLIOPSIDA</subject><subject>Medical sciences</subject><subject>Mustard Gas - analogs & derivatives</subject><subject>Mustard Gas - pharmacokinetics</subject><subject>Mustard Gas - toxicity</subject><subject>NAPHTHALENE</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Oleanolic Acid - analogs & derivatives</subject><subject>Oleanolic Acid - pharmacology</subject><subject>ORGANIC ACIDS</subject><subject>ORGANIC COMPOUNDS</subject><subject>ORGANIC SULFUR COMPOUNDS</subject><subject>ORGANS</subject><subject>PEPTIDES</subject><subject>PLANTS</subject><subject>POLYPEPTIDES</subject><subject>PROTEINS</subject><subject>RADIOPROTECTIVE SUBSTANCES</subject><subject>RESPIRATORY SYSTEM</subject><subject>RESPONSE MODIFYING FACTORS</subject><subject>SKIN</subject><subject>SULFIDES</subject><subject>SULFOXIDES</subject><subject>SULFUR COMPOUNDS</subject><subject>Sulfur mustard</subject><subject>SYNTHESIS</subject><subject>THIOLS</subject><subject>TOXICITY</subject><subject>Toxicology</subject><subject>VEGETABLES</subject><subject>VIABILITY</subject><subject>WEAPONS</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcuO1DAQRSMEYnoGfoAFsoTQwCKh_MhLYoNazUMaCSRAYmc5TmXiJh03tgNkx0ew5ef4EhzSwI6NLV2fuq6qmyT3KGQUaPFknwWljhkDSjMoMqDsRrKhUBcpcM5vJhsAQVOA6sNZcu79HgBqIejt5IzRknEOxSb58cbZgDoYOxJ1rczoA2Gp7gfrLIZ-Hsh6-mnoTIvk0Xa3e_uY_Pz2nZixnTS2RM_BBvvVaBPmKJJ-OqiRfESnghltfEVPmplEba1wxHYk9Eiuhymo0MevkbS4WHRGq9-tHKP-Rc13kludGjzePd0Xyfvnu3fbl-nV6xevts-uUi1EHtJc5LotC8FrXnZYN5y3Le9q0VHecJHXbc0qrUvQDJCWBctRq4bWrMnrSnHQ_CJ5sPpaH4z0cRLUvbbjGDcjGc2rsmJlpC5X6ujspwl9kAfjNQ6DGtFOXlZVRSmImkWSraR21nuHnTw6c1BulhTkkp3cyyU7uWQnoZAxu1h0_2Q_NQds_5b8CSsCD0-A8loNnVOjNv4fJ0QFoqKRe7pyGFf22aBbJsIxZmXcMlBrzf_6-AVxirqa</recordid><startdate>20110901</startdate><enddate>20110901</enddate><creator>Abel, Erika L.</creator><creator>Bubel, Jennifer D.</creator><creator>Simper, Melissa S.</creator><creator>Powell, Leslie</creator><creator>McClellan, S. Alex</creator><creator>Andreeff, Michael</creator><creator>MacLeod, Michael C.</creator><creator>DiGiovanni, John</creator><general>Elsevier Inc</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>7ST</scope><scope>7U7</scope><scope>C1K</scope><scope>SOI</scope><scope>OTOTI</scope></search><sort><creationdate>20110901</creationdate><title>Protection against 2-chloroethyl ethyl sulfide (CEES) — induced cytotoxicity in human keratinocytes by an inducer of the glutathione detoxification pathway</title><author>Abel, Erika L. ; Bubel, Jennifer D. ; Simper, Melissa S. ; Powell, Leslie ; McClellan, S. Alex ; Andreeff, Michael ; MacLeod, Michael C. ; DiGiovanni, John</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-545cd7643937fe9b33dd3f94f13b3459d928cc70c20e17625ecab192b598a30c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>AMINO ACIDS</topic><topic>ANIMAL TISSUES</topic><topic>AROMATICS</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>BODY</topic><topic>BRASSICA</topic><topic>CARBOXYLIC ACIDS</topic><topic>CDDO-Me</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>CHALCOGENIDES</topic><topic>CHELATING AGENTS</topic><topic>Chemical and industrial products toxicology. Toxic occupational diseases</topic><topic>CHEMICAL WARFARE AGENTS</topic><topic>Chemical Warfare Agents - pharmacokinetics</topic><topic>Chemical Warfare Agents - toxicity</topic><topic>CONDENSED AROMATICS</topic><topic>CYSTEINE</topic><topic>Cytotoxicity</topic><topic>DETOXIFICATION</topic><topic>DMSO</topic><topic>Drug Interactions</topic><topic>DRUGS</topic><topic>EDTA</topic><topic>ENZYMES</topic><topic>EPIDERMIS</topic><topic>Epidermis - cytology</topic><topic>Epidermis - drug effects</topic><topic>Epidermis - metabolism</topic><topic>EPITHELIUM</topic><topic>FOOD</topic><topic>Gas, fumes</topic><topic>GLUTATHIONE</topic><topic>Glutathione - metabolism</topic><topic>Humans</topic><topic>HYDROCARBONS</topic><topic>Inactivation, Metabolic</topic><topic>Keratinocytes</topic><topic>Keratinocytes - drug effects</topic><topic>Keratinocytes - metabolism</topic><topic>LIGASES</topic><topic>LUNGS</topic><topic>MAGNOLIOPHYTA</topic><topic>MAGNOLIOPSIDA</topic><topic>Medical sciences</topic><topic>Mustard Gas - analogs & derivatives</topic><topic>Mustard Gas - pharmacokinetics</topic><topic>Mustard Gas - toxicity</topic><topic>NAPHTHALENE</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Oleanolic Acid - analogs & derivatives</topic><topic>Oleanolic Acid - pharmacology</topic><topic>ORGANIC ACIDS</topic><topic>ORGANIC COMPOUNDS</topic><topic>ORGANIC SULFUR COMPOUNDS</topic><topic>ORGANS</topic><topic>PEPTIDES</topic><topic>PLANTS</topic><topic>POLYPEPTIDES</topic><topic>PROTEINS</topic><topic>RADIOPROTECTIVE SUBSTANCES</topic><topic>RESPIRATORY SYSTEM</topic><topic>RESPONSE MODIFYING FACTORS</topic><topic>SKIN</topic><topic>SULFIDES</topic><topic>SULFOXIDES</topic><topic>SULFUR COMPOUNDS</topic><topic>Sulfur mustard</topic><topic>SYNTHESIS</topic><topic>THIOLS</topic><topic>TOXICITY</topic><topic>Toxicology</topic><topic>VEGETABLES</topic><topic>VIABILITY</topic><topic>WEAPONS</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abel, Erika L.</creatorcontrib><creatorcontrib>Bubel, Jennifer D.</creatorcontrib><creatorcontrib>Simper, Melissa S.</creatorcontrib><creatorcontrib>Powell, Leslie</creatorcontrib><creatorcontrib>McClellan, S. Alex</creatorcontrib><creatorcontrib>Andreeff, Michael</creatorcontrib><creatorcontrib>MacLeod, Michael C.</creatorcontrib><creatorcontrib>DiGiovanni, John</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>Environment Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><collection>OSTI.GOV</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abel, Erika L.</au><au>Bubel, Jennifer D.</au><au>Simper, Melissa S.</au><au>Powell, Leslie</au><au>McClellan, S. Alex</au><au>Andreeff, Michael</au><au>MacLeod, Michael C.</au><au>DiGiovanni, John</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protection against 2-chloroethyl ethyl sulfide (CEES) — induced cytotoxicity in human keratinocytes by an inducer of the glutathione detoxification pathway</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2011-09-01</date><risdate>2011</risdate><volume>255</volume><issue>2</issue><spage>176</spage><epage>183</epage><pages>176-183</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><coden>TXAPA9</coden><abstract>Sulfur mustard (SM or mustard gas) was first used as a chemical warfare agent almost 100years ago. Due to its toxic effects on the eyes, lungs, and skin, and the relative ease with which it may be synthesized, mustard gas remains a potential chemical threat to the present day. SM exposed skin develops fluid filled bullae resulting from potent cytotoxicity of cells lining the basement membrane of the epidermis. Currently, there are no antidotes for SM exposure; therefore, chemopreventive measures for first responders following an SM attack are needed. Glutathione (GSH) is known to have a protective effect against SM toxicity, and detoxification of SM is believed to occur, in part, via GSH conjugation. Therefore, we screened 6 potential chemopreventive agents for ability to induce GSH synthesis and protect cultured human keratinocytes against the SM analog, 2-chloroethyl ethyl sulfide (CEES). Using NCTC2544 human keratinocytes, we found that both sulforaphane and methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) stimulated nuclear localization of Nrf2 and induced expression of the GSH synthesis gene, GCLM. Additionally, we found that treatment with CDDO-Me elevated reduced GSH content of NCTC2544 cells and preserved their viability by ~3-fold following exposure to CEES. Our data also suggested that CDDO-Me may act additively with 2,6-dithiopurine (DTP), a nucleophilic scavenging agent, to increase the viability of keratinocytes exposed to CEES. These results suggest that CDDO-Me is a promising chemopreventive agent for SM toxicity in the skin.
► CDDO-Me treatment increased intracellular GSH in human keratinocytes. ► CDDO-Me increased cell viability following exposure to the half-mustard, CEES. ► The cytoprotective effect of CDDO-Me was likely due to scavenging with endogenous GSH.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>21723306</pmid><doi>10.1016/j.taap.2011.06.012</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0041-008X |
| ispartof | Toxicology and applied pharmacology, 2011-09, Vol.255 (2), p.176-183 |
| issn | 0041-008X 1096-0333 |
| language | eng |
| recordid | cdi_osti_scitechconnect_21587827 |
| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | 60 APPLIED LIFE SCIENCES AMINO ACIDS ANIMAL TISSUES AROMATICS Biological and medical sciences Blotting, Western BODY BRASSICA CARBOXYLIC ACIDS CDDO-Me Cell Line Cell Survival - drug effects CHALCOGENIDES CHELATING AGENTS Chemical and industrial products toxicology. Toxic occupational diseases CHEMICAL WARFARE AGENTS Chemical Warfare Agents - pharmacokinetics Chemical Warfare Agents - toxicity CONDENSED AROMATICS CYSTEINE Cytotoxicity DETOXIFICATION DMSO Drug Interactions DRUGS EDTA ENZYMES EPIDERMIS Epidermis - cytology Epidermis - drug effects Epidermis - metabolism EPITHELIUM FOOD Gas, fumes GLUTATHIONE Glutathione - metabolism Humans HYDROCARBONS Inactivation, Metabolic Keratinocytes Keratinocytes - drug effects Keratinocytes - metabolism LIGASES LUNGS MAGNOLIOPHYTA MAGNOLIOPSIDA Medical sciences Mustard Gas - analogs & derivatives Mustard Gas - pharmacokinetics Mustard Gas - toxicity NAPHTHALENE NF-E2-Related Factor 2 - metabolism Oleanolic Acid - analogs & derivatives Oleanolic Acid - pharmacology ORGANIC ACIDS ORGANIC COMPOUNDS ORGANIC SULFUR COMPOUNDS ORGANS PEPTIDES PLANTS POLYPEPTIDES PROTEINS RADIOPROTECTIVE SUBSTANCES RESPIRATORY SYSTEM RESPONSE MODIFYING FACTORS SKIN SULFIDES SULFOXIDES SULFUR COMPOUNDS Sulfur mustard SYNTHESIS THIOLS TOXICITY Toxicology VEGETABLES VIABILITY WEAPONS |
| title | Protection against 2-chloroethyl ethyl sulfide (CEES) — induced cytotoxicity in human keratinocytes by an inducer of the glutathione detoxification pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T05%3A17%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_osti_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Protection%20against%202-chloroethyl%20ethyl%20sulfide%20(CEES)%20%E2%80%94%20induced%20cytotoxicity%20in%20human%20keratinocytes%20by%20an%20inducer%20of%20the%20glutathione%20detoxification%20pathway&rft.jtitle=Toxicology%20and%20applied%20pharmacology&rft.au=Abel,%20Erika%20L.&rft.date=2011-09-01&rft.volume=255&rft.issue=2&rft.spage=176&rft.epage=183&rft.pages=176-183&rft.issn=0041-008X&rft.eissn=1096-0333&rft.coden=TXAPA9&rft_id=info:doi/10.1016/j.taap.2011.06.012&rft_dat=%3Cproquest_osti_%3E888110492%3C/proquest_osti_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=888110492&rft_id=info:pmid/21723306&rft_els_id=S0041008X11002341&rfr_iscdi=true |