Protective Effect of rhIL-11 in a Murine Model of Acetaminophen-Induced Hepatotoxicity
Acetaminophen intoxication results in hepatotoxicity associated with increased serum concentrations of hepatocellular leakage enzymes such as aspartate aminotransferase, lactate dehydrogenase, and alanine aminotransferase, centrilobular degeneration and necrosis, and activation of Kupffer cells. Rec...
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| Veröffentlicht in: | Toxicologic pathology 2001-03, Vol.29 (2), p.242-249 |
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| creator | Trepicchio, William L. Bozza, Mary Bouchard, Page Dorner, Andrew J. |
| description | Acetaminophen intoxication results in hepatotoxicity associated with increased serum concentrations of hepatocellular leakage enzymes such as aspartate aminotransferase, lactate dehydrogenase, and alanine aminotransferase, centrilobular degeneration and necrosis, and activation of Kupffer cells. Recombinant human Interleukin-11 (rhIL-11) downregulates the production of proinfl ammatory mediators from activated macrophages and has direct effects on hepatocyte gene expression. Based on these biological activities of rhIL-11, the effect of pretreatment with rhIL-11 in a murine model of acetaminophen-induce d hepatotoxicity was examined. Administration of 500 ug/kg acetaminophen to B6C3F1 mice resulted in progressive hepatotoxicity as demonstrated by elevated serum concentration s of hepatocellular leakage enzymes and TNFα and histopathology. Pretreatment with 250 or 500 ug/kg of subcutaneously administered rhIL-11 2 hours before acetaminophen administration reduced serum concentrations of hepatocellular leakage enzyme s and TNFα by 40—50%. This was associated with a statistically significant decreas e in mean severity score for centrilobular hemorrhag e and necrosis from grade 3 to grade 2 for rhIL-11-treated animals compared to vehicle. These results indicate that treatment with rhIL-11 has a protective effect in a model of acetaminophen-induce d liver damage. |
| doi_str_mv | 10.1080/019262301317052521 |
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Recombinant human Interleukin-11 (rhIL-11) downregulates the production of proinfl ammatory mediators from activated macrophages and has direct effects on hepatocyte gene expression. Based on these biological activities of rhIL-11, the effect of pretreatment with rhIL-11 in a murine model of acetaminophen-induce d hepatotoxicity was examined. Administration of 500 ug/kg acetaminophen to B6C3F1 mice resulted in progressive hepatotoxicity as demonstrated by elevated serum concentration s of hepatocellular leakage enzymes and TNFα and histopathology. Pretreatment with 250 or 500 ug/kg of subcutaneously administered rhIL-11 2 hours before acetaminophen administration reduced serum concentrations of hepatocellular leakage enzyme s and TNFα by 40—50%. This was associated with a statistically significant decreas e in mean severity score for centrilobular hemorrhag e and necrosis from grade 3 to grade 2 for rhIL-11-treated animals compared to vehicle. These results indicate that treatment with rhIL-11 has a protective effect in a model of acetaminophen-induce d liver damage.</description><identifier>ISSN: 0192-6233</identifier><identifier>EISSN: 1533-1601</identifier><identifier>DOI: 10.1080/019262301317052521</identifier><identifier>PMID: 11421492</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Acetaminophen - toxicity ; Alanine Transaminase - blood ; Animals ; Aspartate Aminotransferases - blood ; Biological and medical sciences ; Chemical and Drug Induced Liver Injury - metabolism ; Chemical and Drug Induced Liver Injury - pathology ; Chemical and Drug Induced Liver Injury - prevention & control ; chemoprotection ; Digestive system ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Down-Regulation ; Female ; Hemorrhage - chemically induced ; Hemorrhage - pathology ; Hemorrhage - prevention & control ; Hepatocytes - drug effects ; Hepatocytes - enzymology ; Hepatocytes - pathology ; Injections, Subcutaneous ; Interleukin-11 - administration & dosage ; Interleukin-11 - therapeutic use ; L-Lactate Dehydrogenase - blood ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Necrosis ; Pharmacology. Drug treatments ; Recombinant Proteins - administration & dosage ; Recombinant Proteins - therapeutic use ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Toxicologic pathology, 2001-03, Vol.29 (2), p.242-249</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-b9e86c708e07e2ec3ae0f5042f690994ebd03e124d363c6d5c2851f2a60cd7b3</citedby><cites>FETCH-LOGICAL-c465t-b9e86c708e07e2ec3ae0f5042f690994ebd03e124d363c6d5c2851f2a60cd7b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1080/019262301317052521$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1080/019262301317052521$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21798,27901,27902,43597,43598</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1035862$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11421492$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Trepicchio, William L.</creatorcontrib><creatorcontrib>Bozza, Mary</creatorcontrib><creatorcontrib>Bouchard, Page</creatorcontrib><creatorcontrib>Dorner, Andrew J.</creatorcontrib><title>Protective Effect of rhIL-11 in a Murine Model of Acetaminophen-Induced Hepatotoxicity</title><title>Toxicologic pathology</title><addtitle>Toxicol Pathol</addtitle><description>Acetaminophen intoxication results in hepatotoxicity associated with increased serum concentrations of hepatocellular leakage enzymes such as aspartate aminotransferase, lactate dehydrogenase, and alanine aminotransferase, centrilobular degeneration and necrosis, and activation of Kupffer cells. Recombinant human Interleukin-11 (rhIL-11) downregulates the production of proinfl ammatory mediators from activated macrophages and has direct effects on hepatocyte gene expression. Based on these biological activities of rhIL-11, the effect of pretreatment with rhIL-11 in a murine model of acetaminophen-induce d hepatotoxicity was examined. Administration of 500 ug/kg acetaminophen to B6C3F1 mice resulted in progressive hepatotoxicity as demonstrated by elevated serum concentration s of hepatocellular leakage enzymes and TNFα and histopathology. Pretreatment with 250 or 500 ug/kg of subcutaneously administered rhIL-11 2 hours before acetaminophen administration reduced serum concentrations of hepatocellular leakage enzyme s and TNFα by 40—50%. This was associated with a statistically significant decreas e in mean severity score for centrilobular hemorrhag e and necrosis from grade 3 to grade 2 for rhIL-11-treated animals compared to vehicle. These results indicate that treatment with rhIL-11 has a protective effect in a model of acetaminophen-induce d liver damage.</description><subject>Acetaminophen - toxicity</subject><subject>Alanine Transaminase - blood</subject><subject>Animals</subject><subject>Aspartate Aminotransferases - blood</subject><subject>Biological and medical sciences</subject><subject>Chemical and Drug Induced Liver Injury - metabolism</subject><subject>Chemical and Drug Induced Liver Injury - pathology</subject><subject>Chemical and Drug Induced Liver Injury - prevention & control</subject><subject>chemoprotection</subject><subject>Digestive system</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Down-Regulation</subject><subject>Female</subject><subject>Hemorrhage - chemically induced</subject><subject>Hemorrhage - pathology</subject><subject>Hemorrhage - prevention & control</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - enzymology</subject><subject>Hepatocytes - pathology</subject><subject>Injections, Subcutaneous</subject><subject>Interleukin-11 - administration & dosage</subject><subject>Interleukin-11 - therapeutic use</subject><subject>L-Lactate Dehydrogenase - blood</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Necrosis</subject><subject>Pharmacology. Drug treatments</subject><subject>Recombinant Proteins - administration & dosage</subject><subject>Recombinant Proteins - therapeutic use</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>0192-6233</issn><issn>1533-1601</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMouq7-AQ_Sg3irO5O0aXsU8WNhRQ-L15KmEzfSNmvSiv57u-yCguBpBuZ534GHsTOEK4QcZoAFl1wACswg5SnHPTbBVIgYJeA-m2yAeCTEETsO4Q0Ac0zgkB0hJhyTgk_Yy7N3PeneflB0a8y4Rc5EfjVfxIiR7SIVPQ7edhQ9upqazfFaU69a27n1irp43tWDpjp6oLXqXe8-rbb91wk7MKoJdLqbU7a8u13ePMSLp_v5zfUi1olM-7gqKJc6g5wgI05aKAKTQsKNLKAoEqpqEIQ8qYUUWtap5nmKhisJus4qMWWX29q1d-8Dhb5sbdDUNKojN4QSs7xIcsFHkG9B7V0Inky59rZV_qtEKDcyy78yx9D5rn2oWqp_Ijt7I3CxA1TQqjFeddqGX9UizeUGm22xoF6pfHOD70Yn_33-BsOZh6E</recordid><startdate>20010301</startdate><enddate>20010301</enddate><creator>Trepicchio, William L.</creator><creator>Bozza, Mary</creator><creator>Bouchard, Page</creator><creator>Dorner, Andrew J.</creator><general>SAGE Publications</general><general>Sage</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>20010301</creationdate><title>Protective Effect of rhIL-11 in a Murine Model of Acetaminophen-Induced Hepatotoxicity</title><author>Trepicchio, William L. ; Bozza, Mary ; Bouchard, Page ; Dorner, Andrew J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-b9e86c708e07e2ec3ae0f5042f690994ebd03e124d363c6d5c2851f2a60cd7b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Acetaminophen - toxicity</topic><topic>Alanine Transaminase - blood</topic><topic>Animals</topic><topic>Aspartate Aminotransferases - blood</topic><topic>Biological and medical sciences</topic><topic>Chemical and Drug Induced Liver Injury - metabolism</topic><topic>Chemical and Drug Induced Liver Injury - pathology</topic><topic>Chemical and Drug Induced Liver Injury - prevention & control</topic><topic>chemoprotection</topic><topic>Digestive system</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Down-Regulation</topic><topic>Female</topic><topic>Hemorrhage - chemically induced</topic><topic>Hemorrhage - pathology</topic><topic>Hemorrhage - prevention & control</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - enzymology</topic><topic>Hepatocytes - pathology</topic><topic>Injections, Subcutaneous</topic><topic>Interleukin-11 - administration & dosage</topic><topic>Interleukin-11 - therapeutic use</topic><topic>L-Lactate Dehydrogenase - blood</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Necrosis</topic><topic>Pharmacology. Drug treatments</topic><topic>Recombinant Proteins - administration & dosage</topic><topic>Recombinant Proteins - therapeutic use</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Trepicchio, William L.</creatorcontrib><creatorcontrib>Bozza, Mary</creatorcontrib><creatorcontrib>Bouchard, Page</creatorcontrib><creatorcontrib>Dorner, Andrew J.</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>Toxicologic pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Trepicchio, William L.</au><au>Bozza, Mary</au><au>Bouchard, Page</au><au>Dorner, Andrew J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective Effect of rhIL-11 in a Murine Model of Acetaminophen-Induced Hepatotoxicity</atitle><jtitle>Toxicologic pathology</jtitle><addtitle>Toxicol Pathol</addtitle><date>2001-03-01</date><risdate>2001</risdate><volume>29</volume><issue>2</issue><spage>242</spage><epage>249</epage><pages>242-249</pages><issn>0192-6233</issn><eissn>1533-1601</eissn><abstract>Acetaminophen intoxication results in hepatotoxicity associated with increased serum concentrations of hepatocellular leakage enzymes such as aspartate aminotransferase, lactate dehydrogenase, and alanine aminotransferase, centrilobular degeneration and necrosis, and activation of Kupffer cells. Recombinant human Interleukin-11 (rhIL-11) downregulates the production of proinfl ammatory mediators from activated macrophages and has direct effects on hepatocyte gene expression. Based on these biological activities of rhIL-11, the effect of pretreatment with rhIL-11 in a murine model of acetaminophen-induce d hepatotoxicity was examined. Administration of 500 ug/kg acetaminophen to B6C3F1 mice resulted in progressive hepatotoxicity as demonstrated by elevated serum concentration s of hepatocellular leakage enzymes and TNFα and histopathology. Pretreatment with 250 or 500 ug/kg of subcutaneously administered rhIL-11 2 hours before acetaminophen administration reduced serum concentrations of hepatocellular leakage enzyme s and TNFα by 40—50%. This was associated with a statistically significant decreas e in mean severity score for centrilobular hemorrhag e and necrosis from grade 3 to grade 2 for rhIL-11-treated animals compared to vehicle. These results indicate that treatment with rhIL-11 has a protective effect in a model of acetaminophen-induce d liver damage.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>11421492</pmid><doi>10.1080/019262301317052521</doi><tpages>8</tpages></addata></record> |
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| source | SAGE Complete A-Z List; MEDLINE; Alma/SFX Local Collection |
| subjects | Acetaminophen - toxicity Alanine Transaminase - blood Animals Aspartate Aminotransferases - blood Biological and medical sciences Chemical and Drug Induced Liver Injury - metabolism Chemical and Drug Induced Liver Injury - pathology Chemical and Drug Induced Liver Injury - prevention & control chemoprotection Digestive system Disease Models, Animal Dose-Response Relationship, Drug Down-Regulation Female Hemorrhage - chemically induced Hemorrhage - pathology Hemorrhage - prevention & control Hepatocytes - drug effects Hepatocytes - enzymology Hepatocytes - pathology Injections, Subcutaneous Interleukin-11 - administration & dosage Interleukin-11 - therapeutic use L-Lactate Dehydrogenase - blood Medical sciences Mice Mice, Inbred BALB C Necrosis Pharmacology. Drug treatments Recombinant Proteins - administration & dosage Recombinant Proteins - therapeutic use Tumor Necrosis Factor-alpha - metabolism |
| title | Protective Effect of rhIL-11 in a Murine Model of Acetaminophen-Induced Hepatotoxicity |
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