Role of glutathione conjugation in 1-bromobutane-induced hepatotoxicity in mice
Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses, or extraction solvents. In the present study, hepatotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were tr...
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| Veröffentlicht in: | Food and chemical toxicology 2010-10, Vol.48 (10), p.2707-2711 |
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| creator | Lee, Sang Kyu Lee, Dong Ju Ko, Gyu Sub Yoo, Se Hyun Ha, Hyun Woo Kang, Mi Jeong Jeong, Tae Cheon |
| description | Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses, or extraction solvents. In the present study, hepatotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500mg/kg in corn oil once for dose–response study or treated orally with 1-BB at 1500mg/kg for 6, 12, 24 and 48h for time–course study. Three kinds of GSH conjugates, including S-butyl GSH, S-butyl cysteine, and (hydroxybutyl)mercapturic acid, were identified in livers by liquid chromatography–electrospray ionization-tandem mass spectrometry. When the production of S-butyl GSH from 1-BB was investigated in the liver, the conjugate was detected maximally 6h after treatment. Hepatic GSH levels were almost depleted by single treatment with 1-BB within 6h. Treatment of mice with 1-BB increased in serum activities of alanine aminotransferase and aspartate aminotransferase dose-dependently. Hepatic contents of thiobarbituric acid reactive substances were significantly increased by 1-BB at 12 and 24h after treatment. Our present results suggested that 1-BB could cause hepatotoxicity as well as depletion of GSH content, due to the formation of GSH conjugates with 1-BB in mice. |
| doi_str_mv | 10.1016/j.fct.2010.06.044 |
| format | Article |
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In the present study, hepatotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500mg/kg in corn oil once for dose–response study or treated orally with 1-BB at 1500mg/kg for 6, 12, 24 and 48h for time–course study. Three kinds of GSH conjugates, including S-butyl GSH, S-butyl cysteine, and (hydroxybutyl)mercapturic acid, were identified in livers by liquid chromatography–electrospray ionization-tandem mass spectrometry. When the production of S-butyl GSH from 1-BB was investigated in the liver, the conjugate was detected maximally 6h after treatment. Hepatic GSH levels were almost depleted by single treatment with 1-BB within 6h. Treatment of mice with 1-BB increased in serum activities of alanine aminotransferase and aspartate aminotransferase dose-dependently. Hepatic contents of thiobarbituric acid reactive substances were significantly increased by 1-BB at 12 and 24h after treatment. Our present results suggested that 1-BB could cause hepatotoxicity as well as depletion of GSH content, due to the formation of GSH conjugates with 1-BB in mice.</description><identifier>ISSN: 0278-6915</identifier><identifier>EISSN: 1873-6351</identifier><identifier>DOI: 10.1016/j.fct.2010.06.044</identifier><identifier>PMID: 20600521</identifier><identifier>CODEN: FCTOD7</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>1-Bromobutane ; Alanine Transaminase - blood ; Animals ; Aspartate Aminotransferases - blood ; Biological and medical sciences ; Body Weight - drug effects ; Chemical and Drug Induced Liver Injury - metabolism ; Chromatography, High Pressure Liquid ; Conjugation ; Dose-Response Relationship, Drug ; Female ; Glutathione ; Glutathione - metabolism ; Hepatotoxicity ; Hydrocarbons, Brominated - toxicity ; In vivo ; Liver - metabolism ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Organ Size - drug effects ; Spectrometry, Mass, Electrospray Ionization ; Toxicology</subject><ispartof>Food and chemical toxicology, 2010-10, Vol.48 (10), p.2707-2711</ispartof><rights>2010 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright (c) 2010 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c480t-b12a9f7c4ea621788b3159a860badd806b2e5a7bd42eb63e1d7d950cd273e1cc3</citedby><cites>FETCH-LOGICAL-c480t-b12a9f7c4ea621788b3159a860badd806b2e5a7bd42eb63e1d7d950cd273e1cc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0278691510004187$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23324990$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20600521$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Sang Kyu</creatorcontrib><creatorcontrib>Lee, Dong Ju</creatorcontrib><creatorcontrib>Ko, Gyu Sub</creatorcontrib><creatorcontrib>Yoo, Se Hyun</creatorcontrib><creatorcontrib>Ha, Hyun Woo</creatorcontrib><creatorcontrib>Kang, Mi Jeong</creatorcontrib><creatorcontrib>Jeong, Tae Cheon</creatorcontrib><title>Role of glutathione conjugation in 1-bromobutane-induced hepatotoxicity in mice</title><title>Food and chemical toxicology</title><addtitle>Food Chem Toxicol</addtitle><description>Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses, or extraction solvents. In the present study, hepatotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500mg/kg in corn oil once for dose–response study or treated orally with 1-BB at 1500mg/kg for 6, 12, 24 and 48h for time–course study. Three kinds of GSH conjugates, including S-butyl GSH, S-butyl cysteine, and (hydroxybutyl)mercapturic acid, were identified in livers by liquid chromatography–electrospray ionization-tandem mass spectrometry. When the production of S-butyl GSH from 1-BB was investigated in the liver, the conjugate was detected maximally 6h after treatment. Hepatic GSH levels were almost depleted by single treatment with 1-BB within 6h. Treatment of mice with 1-BB increased in serum activities of alanine aminotransferase and aspartate aminotransferase dose-dependently. Hepatic contents of thiobarbituric acid reactive substances were significantly increased by 1-BB at 12 and 24h after treatment. Our present results suggested that 1-BB could cause hepatotoxicity as well as depletion of GSH content, due to the formation of GSH conjugates with 1-BB in mice.</description><subject>1-Bromobutane</subject><subject>Alanine Transaminase - blood</subject><subject>Animals</subject><subject>Aspartate Aminotransferases - blood</subject><subject>Biological and medical sciences</subject><subject>Body Weight - drug effects</subject><subject>Chemical and Drug Induced Liver Injury - metabolism</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Conjugation</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Glutathione</subject><subject>Glutathione - metabolism</subject><subject>Hepatotoxicity</subject><subject>Hydrocarbons, Brominated - toxicity</subject><subject>In vivo</subject><subject>Liver - metabolism</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred ICR</subject><subject>Organ Size - drug effects</subject><subject>Spectrometry, Mass, Electrospray Ionization</subject><subject>Toxicology</subject><issn>0278-6915</issn><issn>1873-6351</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1r3DAQhkVoSLZJfkAvxZeSkzcjyZZseiqhaQqBQEjOQh_jRIttbSU5NP8-Wnbb3noaXnjemeEh5BOFNQUqrjbrweY1g5JBrKFpjsiKdpLXgrf0A1kBk10tetqeko8pbQBAUilOyCkDAdAyuiL3D2HEKgzV87hknV98mLGyYd4szzqXUPm5orWJYQqmADPWfnaLRVe94FbnkMNvb31-23GTt3hOjgc9Jrw4zDPydPP98fq2vrv_8fP6211tmw5ybSjT_SBtg1owKrvOcNr2uhNgtHMdCMOw1dK4hqERHKmTrm_BOiZLsJafkcv93m0MvxZMWU0-WRzH8mJYkpKdZJyLlhWS7kkbQ0oRB7WNftLxTVFQO41qo4pGtdOoQKiisXQ-H7YvZkL3t_HHWwG-HACdrB6HqGfr0z-Oc9b0PRTu657D4uLVY1TJepyLPx-xHHXB_-eNd_n-kE0</recordid><startdate>20101001</startdate><enddate>20101001</enddate><creator>Lee, Sang Kyu</creator><creator>Lee, Dong Ju</creator><creator>Ko, Gyu Sub</creator><creator>Yoo, Se Hyun</creator><creator>Ha, Hyun Woo</creator><creator>Kang, Mi Jeong</creator><creator>Jeong, Tae Cheon</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>7T2</scope><scope>7U2</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20101001</creationdate><title>Role of glutathione conjugation in 1-bromobutane-induced hepatotoxicity in mice</title><author>Lee, Sang Kyu ; Lee, Dong Ju ; Ko, Gyu Sub ; Yoo, Se Hyun ; Ha, Hyun Woo ; Kang, Mi Jeong ; Jeong, Tae Cheon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c480t-b12a9f7c4ea621788b3159a860badd806b2e5a7bd42eb63e1d7d950cd273e1cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>1-Bromobutane</topic><topic>Alanine Transaminase - blood</topic><topic>Animals</topic><topic>Aspartate Aminotransferases - blood</topic><topic>Biological and medical sciences</topic><topic>Body Weight - drug effects</topic><topic>Chemical and Drug Induced Liver Injury - metabolism</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Conjugation</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Glutathione</topic><topic>Glutathione - metabolism</topic><topic>Hepatotoxicity</topic><topic>Hydrocarbons, Brominated - toxicity</topic><topic>In vivo</topic><topic>Liver - metabolism</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred ICR</topic><topic>Organ Size - drug effects</topic><topic>Spectrometry, Mass, Electrospray Ionization</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Sang Kyu</creatorcontrib><creatorcontrib>Lee, Dong Ju</creatorcontrib><creatorcontrib>Ko, Gyu Sub</creatorcontrib><creatorcontrib>Yoo, Se Hyun</creatorcontrib><creatorcontrib>Ha, Hyun Woo</creatorcontrib><creatorcontrib>Kang, Mi Jeong</creatorcontrib><creatorcontrib>Jeong, Tae Cheon</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>Health and Safety Science Abstracts (Full archive)</collection><collection>Safety Science and Risk</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>Lee, Sang Kyu</au><au>Lee, Dong Ju</au><au>Ko, Gyu Sub</au><au>Yoo, Se Hyun</au><au>Ha, Hyun Woo</au><au>Kang, Mi Jeong</au><au>Jeong, Tae Cheon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of glutathione conjugation in 1-bromobutane-induced hepatotoxicity in mice</atitle><jtitle>Food and chemical toxicology</jtitle><addtitle>Food Chem Toxicol</addtitle><date>2010-10-01</date><risdate>2010</risdate><volume>48</volume><issue>10</issue><spage>2707</spage><epage>2711</epage><pages>2707-2711</pages><issn>0278-6915</issn><eissn>1873-6351</eissn><coden>FCTOD7</coden><abstract>Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses, or extraction solvents. In the present study, hepatotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500mg/kg in corn oil once for dose–response study or treated orally with 1-BB at 1500mg/kg for 6, 12, 24 and 48h for time–course study. Three kinds of GSH conjugates, including S-butyl GSH, S-butyl cysteine, and (hydroxybutyl)mercapturic acid, were identified in livers by liquid chromatography–electrospray ionization-tandem mass spectrometry. When the production of S-butyl GSH from 1-BB was investigated in the liver, the conjugate was detected maximally 6h after treatment. Hepatic GSH levels were almost depleted by single treatment with 1-BB within 6h. Treatment of mice with 1-BB increased in serum activities of alanine aminotransferase and aspartate aminotransferase dose-dependently. Hepatic contents of thiobarbituric acid reactive substances were significantly increased by 1-BB at 12 and 24h after treatment. Our present results suggested that 1-BB could cause hepatotoxicity as well as depletion of GSH content, due to the formation of GSH conjugates with 1-BB in mice.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>20600521</pmid><doi>10.1016/j.fct.2010.06.044</doi><tpages>5</tpages></addata></record> |
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| subjects | 1-Bromobutane Alanine Transaminase - blood Animals Aspartate Aminotransferases - blood Biological and medical sciences Body Weight - drug effects Chemical and Drug Induced Liver Injury - metabolism Chromatography, High Pressure Liquid Conjugation Dose-Response Relationship, Drug Female Glutathione Glutathione - metabolism Hepatotoxicity Hydrocarbons, Brominated - toxicity In vivo Liver - metabolism Medical sciences Mice Mice, Inbred BALB C Mice, Inbred ICR Organ Size - drug effects Spectrometry, Mass, Electrospray Ionization Toxicology |
| title | Role of glutathione conjugation in 1-bromobutane-induced hepatotoxicity in mice |
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