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Morphine Enhances Doxorubicin-Induced Cardiotoxicity in the Rat
Interventions to reduce the cardiotoxicity of doxorubicin are clinically relevant. Pharmacological preconditioning mimicking ischemic preconditioning has been demonstrated with morphine and represents an acceptable clinical intervention. The purpose of this study was to examine if pretreatment in vi...
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| Published in: | Cardiovascular toxicology 2014-09, Vol.14 (3), p.251-259 |
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| container_title | Cardiovascular toxicology |
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| creator | Hole, Lisa Drange Larsen, Terje Hjalmar Fossan, Kjell Ove Limé, Fredrik Schjøtt, Jan |
| description | Interventions to reduce the cardiotoxicity of doxorubicin are clinically relevant. Pharmacological preconditioning mimicking ischemic preconditioning has been demonstrated with morphine and represents an acceptable clinical intervention. The purpose of this study was to examine if pretreatment in vivo with morphine could reduce doxorubicin-induced cardiotoxicity ex vivo in a rat model. Wistar rats were divided into six groups and pretreated with an intraperitoneal (i.p.) injection of 3 or 10 mg/kg morphine, 1 mg/kg naloxone and saline, 1 mg/kg naloxone and 3 mg/kg morphine or saline, 60 min before excision of the heart. Biochemical indices such as troponin T (TnT) and hydrogen peroxide (H
2
O
2
) in effluate were measured together with physiological parameters in Langendorff hearts before and after doxorubicin infusion (2 mg/mL 0.05 mL/min for 45 min). Myocardial content of doxorubicin was measured at the end of infusion. Pretreatment with morphine, irrespective of dosage, produced a significant loss in left ventricular-developed pressure and an increase of TnT and H
2
O
2
in effluate before doxorubicin infusion (
p
|
| doi_str_mv | 10.1007/s12012-014-9249-z |
| format | article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4133639</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A718102113</galeid><sourcerecordid>A718102113</sourcerecordid><originalsourceid>FETCH-LOGICAL-c710t-898ee3aa4fc8a71a8badcce81b669b3d9f41dd3aebc0af7331ba04e01cdc527c3</originalsourceid><addsrcrecordid>eNp1UU1v1DAQtRCIloUfwAVF4sIlxeOPJL6AqqUtlYqQEJwtx57susrai51UbX89Xm0pLQL5YGvmvTd-8wh5DfQIKG3fZ2AUWE1B1IoJVd8-IYcgpaopk-rp7s1p3SoqD8iLnC8pZYw18jk5YEJyUK08JB-_xLRd-4DVSVibYDFXn-J1THPvrQ_1eXCzRVctTXI-TvG6VKebyodqWmP1zUwvybPBjBlf3d0L8uP05Pvyc33x9ex8eXxR2xboVHeqQ-TGiMF2pgXT9cZZix30TaN67tQgwDlusLfUDC3n0BsqkIJ1VrLW8gX5sNfdzv0GncUwJTPqbfIbk250NF4_7gS_1qt4pQVw3nBVBN7dCaT4c8Y86Y3PFsfRBIxz1iCbskdgQhTo27-gl3FOodgrKMmZEmX5f1ArM6L2YYhlrt2J6uMWOqAMyugFOfoHqhyHG29jwMGX-iMC7Ak2xZwTDvcegepd6nqfui6_1bvU9W3hvHm4nHvG75gLgO0BubTCCtMDR_9V_QVIxbfi</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1553294007</pqid></control><display><type>article</type><title>Morphine Enhances Doxorubicin-Induced Cardiotoxicity in the Rat</title><source>Springer Nature</source><creator>Hole, Lisa Drange ; Larsen, Terje Hjalmar ; Fossan, Kjell Ove ; Limé, Fredrik ; Schjøtt, Jan</creator><creatorcontrib>Hole, Lisa Drange ; Larsen, Terje Hjalmar ; Fossan, Kjell Ove ; Limé, Fredrik ; Schjøtt, Jan</creatorcontrib><description>Interventions to reduce the cardiotoxicity of doxorubicin are clinically relevant. Pharmacological preconditioning mimicking ischemic preconditioning has been demonstrated with morphine and represents an acceptable clinical intervention. The purpose of this study was to examine if pretreatment in vivo with morphine could reduce doxorubicin-induced cardiotoxicity ex vivo in a rat model. Wistar rats were divided into six groups and pretreated with an intraperitoneal (i.p.) injection of 3 or 10 mg/kg morphine, 1 mg/kg naloxone and saline, 1 mg/kg naloxone and 3 mg/kg morphine or saline, 60 min before excision of the heart. Biochemical indices such as troponin T (TnT) and hydrogen peroxide (H
2
O
2
) in effluate were measured together with physiological parameters in Langendorff hearts before and after doxorubicin infusion (2 mg/mL 0.05 mL/min for 45 min). Myocardial content of doxorubicin was measured at the end of infusion. Pretreatment with morphine, irrespective of dosage, produced a significant loss in left ventricular-developed pressure and an increase of TnT and H
2
O
2
in effluate before doxorubicin infusion (
p
< 0.05). Morphine also produced a significant increase in left ventricular end-diastolic pressure and an increase of TnT and H
2
O
2
in effluate (
p
< 0.05) at the end of doxorubicin infusion. Naloxone, a non-selective opioid receptor antagonist, abolished the effects of morphine both before and after doxorubicin infusion. Morphine, irrespective of dosage, increased myocardial content of doxorubicin compared to pretreatment with saline (
p
< 0.05). Pretreatment with morphine is associated with a cardiodepressive effect and enhances cardiotoxicity of doxorubicin measured by increased myocardial accumulation of doxorubicin and physiological and biochemical indices. The negative effects observed in our rat model are abolished by naloxone.</description><identifier>ISSN: 1530-7905</identifier><identifier>EISSN: 1559-0259</identifier><identifier>DOI: 10.1007/s12012-014-9249-z</identifier><identifier>PMID: 24531975</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Animals ; Antibiotics, Antineoplastic - toxicity ; Antimitotic agents ; Antineoplastic agents ; Biomarkers ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Cardiology ; Cardiotoxicity ; Cardiotoxicity - pathology ; Disease Models, Animal ; Doxorubicin - toxicity ; Drug Synergism ; Heart ; Heart Diseases - blood ; Heart Diseases - drug therapy ; Hydrogen peroxide ; Hydrogen Peroxide - metabolism ; Ischemia ; Laboratory animals ; Male ; Morphine ; Morphine - pharmacology ; Naloxone - pharmacology ; Narcotic Antagonists - pharmacology ; Narcotics ; Narcotics - pharmacology ; Pharmacology/Toxicology ; Physiology ; Pilot projects ; Rats ; Rats, Wistar ; Troponin T - blood</subject><ispartof>Cardiovascular toxicology, 2014-09, Vol.14 (3), p.251-259</ispartof><rights>The Author(s) 2014</rights><rights>COPYRIGHT 2014 Springer</rights><rights>Springer Science+Business Media New York 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c710t-898ee3aa4fc8a71a8badcce81b669b3d9f41dd3aebc0af7331ba04e01cdc527c3</citedby><cites>FETCH-LOGICAL-c710t-898ee3aa4fc8a71a8badcce81b669b3d9f41dd3aebc0af7331ba04e01cdc527c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24531975$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hole, Lisa Drange</creatorcontrib><creatorcontrib>Larsen, Terje Hjalmar</creatorcontrib><creatorcontrib>Fossan, Kjell Ove</creatorcontrib><creatorcontrib>Limé, Fredrik</creatorcontrib><creatorcontrib>Schjøtt, Jan</creatorcontrib><title>Morphine Enhances Doxorubicin-Induced Cardiotoxicity in the Rat</title><title>Cardiovascular toxicology</title><addtitle>Cardiovasc Toxicol</addtitle><addtitle>Cardiovasc Toxicol</addtitle><description>Interventions to reduce the cardiotoxicity of doxorubicin are clinically relevant. Pharmacological preconditioning mimicking ischemic preconditioning has been demonstrated with morphine and represents an acceptable clinical intervention. The purpose of this study was to examine if pretreatment in vivo with morphine could reduce doxorubicin-induced cardiotoxicity ex vivo in a rat model. Wistar rats were divided into six groups and pretreated with an intraperitoneal (i.p.) injection of 3 or 10 mg/kg morphine, 1 mg/kg naloxone and saline, 1 mg/kg naloxone and 3 mg/kg morphine or saline, 60 min before excision of the heart. Biochemical indices such as troponin T (TnT) and hydrogen peroxide (H
2
O
2
) in effluate were measured together with physiological parameters in Langendorff hearts before and after doxorubicin infusion (2 mg/mL 0.05 mL/min for 45 min). Myocardial content of doxorubicin was measured at the end of infusion. Pretreatment with morphine, irrespective of dosage, produced a significant loss in left ventricular-developed pressure and an increase of TnT and H
2
O
2
in effluate before doxorubicin infusion (
p
< 0.05). Morphine also produced a significant increase in left ventricular end-diastolic pressure and an increase of TnT and H
2
O
2
in effluate (
p
< 0.05) at the end of doxorubicin infusion. Naloxone, a non-selective opioid receptor antagonist, abolished the effects of morphine both before and after doxorubicin infusion. Morphine, irrespective of dosage, increased myocardial content of doxorubicin compared to pretreatment with saline (
p
< 0.05). Pretreatment with morphine is associated with a cardiodepressive effect and enhances cardiotoxicity of doxorubicin measured by increased myocardial accumulation of doxorubicin and physiological and biochemical indices. The negative effects observed in our rat model are abolished by naloxone.</description><subject>Animals</subject><subject>Antibiotics, Antineoplastic - toxicity</subject><subject>Antimitotic agents</subject><subject>Antineoplastic agents</subject><subject>Biomarkers</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Cardiology</subject><subject>Cardiotoxicity</subject><subject>Cardiotoxicity - pathology</subject><subject>Disease Models, Animal</subject><subject>Doxorubicin - toxicity</subject><subject>Drug Synergism</subject><subject>Heart</subject><subject>Heart Diseases - blood</subject><subject>Heart Diseases - drug therapy</subject><subject>Hydrogen peroxide</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>Ischemia</subject><subject>Laboratory animals</subject><subject>Male</subject><subject>Morphine</subject><subject>Morphine - pharmacology</subject><subject>Naloxone - pharmacology</subject><subject>Narcotic Antagonists - pharmacology</subject><subject>Narcotics</subject><subject>Narcotics - pharmacology</subject><subject>Pharmacology/Toxicology</subject><subject>Physiology</subject><subject>Pilot projects</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Troponin T - blood</subject><issn>1530-7905</issn><issn>1559-0259</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNp1UU1v1DAQtRCIloUfwAVF4sIlxeOPJL6AqqUtlYqQEJwtx57susrai51UbX89Xm0pLQL5YGvmvTd-8wh5DfQIKG3fZ2AUWE1B1IoJVd8-IYcgpaopk-rp7s1p3SoqD8iLnC8pZYw18jk5YEJyUK08JB-_xLRd-4DVSVibYDFXn-J1THPvrQ_1eXCzRVctTXI-TvG6VKebyodqWmP1zUwvybPBjBlf3d0L8uP05Pvyc33x9ex8eXxR2xboVHeqQ-TGiMF2pgXT9cZZix30TaN67tQgwDlusLfUDC3n0BsqkIJ1VrLW8gX5sNfdzv0GncUwJTPqbfIbk250NF4_7gS_1qt4pQVw3nBVBN7dCaT4c8Y86Y3PFsfRBIxz1iCbskdgQhTo27-gl3FOodgrKMmZEmX5f1ArM6L2YYhlrt2J6uMWOqAMyugFOfoHqhyHG29jwMGX-iMC7Ak2xZwTDvcegepd6nqfui6_1bvU9W3hvHm4nHvG75gLgO0BubTCCtMDR_9V_QVIxbfi</recordid><startdate>20140901</startdate><enddate>20140901</enddate><creator>Hole, Lisa Drange</creator><creator>Larsen, Terje Hjalmar</creator><creator>Fossan, Kjell Ove</creator><creator>Limé, Fredrik</creator><creator>Schjøtt, Jan</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>C6C</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7U7</scope><scope>C1K</scope><scope>5PM</scope></search><sort><creationdate>20140901</creationdate><title>Morphine Enhances Doxorubicin-Induced Cardiotoxicity in the Rat</title><author>Hole, Lisa Drange ; Larsen, Terje Hjalmar ; Fossan, Kjell Ove ; Limé, Fredrik ; Schjøtt, Jan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c710t-898ee3aa4fc8a71a8badcce81b669b3d9f41dd3aebc0af7331ba04e01cdc527c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Antibiotics, Antineoplastic - toxicity</topic><topic>Antimitotic agents</topic><topic>Antineoplastic agents</topic><topic>Biomarkers</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Cardiology</topic><topic>Cardiotoxicity</topic><topic>Cardiotoxicity - pathology</topic><topic>Disease Models, Animal</topic><topic>Doxorubicin - toxicity</topic><topic>Drug Synergism</topic><topic>Heart</topic><topic>Heart Diseases - blood</topic><topic>Heart Diseases - drug therapy</topic><topic>Hydrogen peroxide</topic><topic>Hydrogen Peroxide - metabolism</topic><topic>Ischemia</topic><topic>Laboratory animals</topic><topic>Male</topic><topic>Morphine</topic><topic>Morphine - pharmacology</topic><topic>Naloxone - pharmacology</topic><topic>Narcotic Antagonists - pharmacology</topic><topic>Narcotics</topic><topic>Narcotics - pharmacology</topic><topic>Pharmacology/Toxicology</topic><topic>Physiology</topic><topic>Pilot projects</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Troponin T - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hole, Lisa Drange</creatorcontrib><creatorcontrib>Larsen, Terje Hjalmar</creatorcontrib><creatorcontrib>Fossan, Kjell Ove</creatorcontrib><creatorcontrib>Limé, Fredrik</creatorcontrib><creatorcontrib>Schjøtt, Jan</creatorcontrib><collection>SpringerOpen</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cardiovascular toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hole, Lisa Drange</au><au>Larsen, Terje Hjalmar</au><au>Fossan, Kjell Ove</au><au>Limé, Fredrik</au><au>Schjøtt, Jan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Morphine Enhances Doxorubicin-Induced Cardiotoxicity in the Rat</atitle><jtitle>Cardiovascular toxicology</jtitle><stitle>Cardiovasc Toxicol</stitle><addtitle>Cardiovasc Toxicol</addtitle><date>2014-09-01</date><risdate>2014</risdate><volume>14</volume><issue>3</issue><spage>251</spage><epage>259</epage><pages>251-259</pages><issn>1530-7905</issn><eissn>1559-0259</eissn><abstract>Interventions to reduce the cardiotoxicity of doxorubicin are clinically relevant. Pharmacological preconditioning mimicking ischemic preconditioning has been demonstrated with morphine and represents an acceptable clinical intervention. The purpose of this study was to examine if pretreatment in vivo with morphine could reduce doxorubicin-induced cardiotoxicity ex vivo in a rat model. Wistar rats were divided into six groups and pretreated with an intraperitoneal (i.p.) injection of 3 or 10 mg/kg morphine, 1 mg/kg naloxone and saline, 1 mg/kg naloxone and 3 mg/kg morphine or saline, 60 min before excision of the heart. Biochemical indices such as troponin T (TnT) and hydrogen peroxide (H
2
O
2
) in effluate were measured together with physiological parameters in Langendorff hearts before and after doxorubicin infusion (2 mg/mL 0.05 mL/min for 45 min). Myocardial content of doxorubicin was measured at the end of infusion. Pretreatment with morphine, irrespective of dosage, produced a significant loss in left ventricular-developed pressure and an increase of TnT and H
2
O
2
in effluate before doxorubicin infusion (
p
< 0.05). Morphine also produced a significant increase in left ventricular end-diastolic pressure and an increase of TnT and H
2
O
2
in effluate (
p
< 0.05) at the end of doxorubicin infusion. Naloxone, a non-selective opioid receptor antagonist, abolished the effects of morphine both before and after doxorubicin infusion. Morphine, irrespective of dosage, increased myocardial content of doxorubicin compared to pretreatment with saline (
p
< 0.05). Pretreatment with morphine is associated with a cardiodepressive effect and enhances cardiotoxicity of doxorubicin measured by increased myocardial accumulation of doxorubicin and physiological and biochemical indices. The negative effects observed in our rat model are abolished by naloxone.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>24531975</pmid><doi>10.1007/s12012-014-9249-z</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cardiovascular toxicology, 2014-09, Vol.14 (3), p.251-259 |
| issn | 1530-7905 1559-0259 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4133639 |
| source | Springer Nature |
| subjects | Animals Antibiotics, Antineoplastic - toxicity Antimitotic agents Antineoplastic agents Biomarkers Biomedical and Life Sciences Biomedicine Cancer Cardiology Cardiotoxicity Cardiotoxicity - pathology Disease Models, Animal Doxorubicin - toxicity Drug Synergism Heart Heart Diseases - blood Heart Diseases - drug therapy Hydrogen peroxide Hydrogen Peroxide - metabolism Ischemia Laboratory animals Male Morphine Morphine - pharmacology Naloxone - pharmacology Narcotic Antagonists - pharmacology Narcotics Narcotics - pharmacology Pharmacology/Toxicology Physiology Pilot projects Rats Rats, Wistar Troponin T - blood |
| title | Morphine Enhances Doxorubicin-Induced Cardiotoxicity in the Rat |
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