Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore
Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocar...
Gespeichert in:
| Veröffentlicht in: | Toxicology and applied pharmacology 2013-04, Vol.268 (2), p.149-156 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 156 |
|---|---|
| container_issue | 2 |
| container_start_page | 149 |
| container_title | Toxicology and applied pharmacology |
| container_volume | 268 |
| creator | Gharanei, M. Hussain, A. Janneh, O. Maddock, H.L. |
| description | Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocardial ischaemia reperfusion and the mechanistic basis of protection, in particular the role of the mitochondrial permeability transition pore (mPTP) in such protection. The effects of doxorubicin (1μM)±cyclosporine A (CsA, 0.2μM; inhibits mPTP) were investigated in isolated male Sprague–Dawley rats using Langendorff heart and papillary muscle contraction models subjected to simulated ischaemia and reperfusion injury. Isolated rat cardiac myocytes were used in an oxidative stress model to study the effects of drug treatment on mPTP by confocal microscopy. Western blot analysis evaluated the effects of drug treatment on p-Akt and p-Erk 1/2 levels. Langendorff and the isometric contraction models showed a detrimental effect of doxorubicin throughout reperfusion/reoxygenation as well as increased p-Akt and p-Erk levels. Interestingly, CsA not only reversed the detrimental effects of doxorubicin, but also reduced p-Akt and p-Erk levels. In the sustained oxidative stress assay to study mPTP opening, doxorubicin decreased the time taken to depolarization and hypercontracture, but these effects were delayed in the presence of CsA. Collectively, our data suggest for the first that doxorubicin exacerbates myocardial injury in an ischaemia reperfusion model. If the inhibition of mPTP ameliorates the cardiotoxic effects of doxorubicin, then more selective inhibitors of mPTP should be further investigated for their utility in patients receiving doxorubicin.
► Doxorubicin exacerbates myocardial ischaemia reperfusion injury. ► Co-treatment with CsA protects against doxorubicin induced myocardial injury. ► CsA delays doxorubicin induced mPTP opening in laser induced stress model. ► Doxorubicin causes increase in p-Akt and p-Erk levels during reperfusion injury. ► CsA or other mPTP inhibitors may be useful against drug-induced cardiotoxicity. |
| doi_str_mv | 10.1016/j.taap.2012.12.003 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_osti_</sourceid><recordid>TN_cdi_osti_scitechconnect_22285270</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0041008X12005303</els_id><sourcerecordid>1323812309</sourcerecordid><originalsourceid>FETCH-LOGICAL-c447t-674d7d1d1d5b8c69bc799b4e7fb10f1e13d70bcd5732e890dd2ff80fa9f46a283</originalsourceid><addsrcrecordid>eNp9kcuqFDEQhoMonnH0BVxIQAQ3PVaSnr6AGzle4YAbBXchnVScDN1Jm6SPZx7CdzbNjLqTFASqvvqpqp-Qpwx2DFjz6rjLSs07DozvSgCIe2TDoG8qEELcJxuAmlUA3bcr8iilIwD0dc0ekisueMNZ12zIr7fhLsRlcNp56rxZNBo6nYJW0Tg1ltRxiSfqEsU7pTEOKhfAhnEMP53_Xgr6oHBymqYcMSV66xQNM_q1GCzNB6STy0EfgjdxVZwxTqgGN7p8ojkqn1x2wdM5RHxMHlg1Jnxy-bfk6_t3X64_VjefP3y6fnNT6bpuc9W0tWkNK28_dLrpB932_VBjawcGliETpoVBm30rOHY9GMOt7cCq3taN4p3Ykudn3ZCyk0m7jPqgg_eos-Scd3veQqFenqk5hh8Lpiynsi6Oo_IYliSZ4KJjXEBfUH5GdQwpRbRyjm5S8SQZyNUseZSrWXI1S5YoZpWmZxf9ZZjQ_G35404BXlwAlbQabTmWdukf1_KO92WALXl95rDc7NZhXFdCX6x0cd3IBPe_OX4DIUO2VA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1323812309</pqid></control><display><type>article</type><title>Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Gharanei, M. ; Hussain, A. ; Janneh, O. ; Maddock, H.L.</creator><creatorcontrib>Gharanei, M. ; Hussain, A. ; Janneh, O. ; Maddock, H.L.</creatorcontrib><description>Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocardial ischaemia reperfusion and the mechanistic basis of protection, in particular the role of the mitochondrial permeability transition pore (mPTP) in such protection. The effects of doxorubicin (1μM)±cyclosporine A (CsA, 0.2μM; inhibits mPTP) were investigated in isolated male Sprague–Dawley rats using Langendorff heart and papillary muscle contraction models subjected to simulated ischaemia and reperfusion injury. Isolated rat cardiac myocytes were used in an oxidative stress model to study the effects of drug treatment on mPTP by confocal microscopy. Western blot analysis evaluated the effects of drug treatment on p-Akt and p-Erk 1/2 levels. Langendorff and the isometric contraction models showed a detrimental effect of doxorubicin throughout reperfusion/reoxygenation as well as increased p-Akt and p-Erk levels. Interestingly, CsA not only reversed the detrimental effects of doxorubicin, but also reduced p-Akt and p-Erk levels. In the sustained oxidative stress assay to study mPTP opening, doxorubicin decreased the time taken to depolarization and hypercontracture, but these effects were delayed in the presence of CsA. Collectively, our data suggest for the first that doxorubicin exacerbates myocardial injury in an ischaemia reperfusion model. If the inhibition of mPTP ameliorates the cardiotoxic effects of doxorubicin, then more selective inhibitors of mPTP should be further investigated for their utility in patients receiving doxorubicin.
► Doxorubicin exacerbates myocardial ischaemia reperfusion injury. ► Co-treatment with CsA protects against doxorubicin induced myocardial injury. ► CsA delays doxorubicin induced mPTP opening in laser induced stress model. ► Doxorubicin causes increase in p-Akt and p-Erk levels during reperfusion injury. ► CsA or other mPTP inhibitors may be useful against drug-induced cardiotoxicity.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2012.12.003</identifier><identifier>PMID: 23262186</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ADENINES ; Animals ; ANOXIA ; Anthracycline ; Antibiotics, Antineoplastic - toxicity ; APOPTOSIS ; ATP ; Biological and medical sciences ; Cancer ; Cardiac muscle ; Cardiology. Vascular system ; cardiomyocytes ; Cell death ; Chemotherapy ; Confocal microscopy ; Cyclophilin D ; Cyclosporin A ; CYCLOSPORINE ; Data processing ; DEPOLARIZATION ; DOXORUBICIN ; Doxorubicin - toxicity ; Drugs ; Extracellular Signal-Regulated MAP Kinases - metabolism ; HEART ; Hemodynamics - drug effects ; Injuries ; Ischaemia ; Ischemia ; Male ; Medical sciences ; MITOCHONDRIA ; Mitochondrial Membrane Transport Proteins - drug effects ; Mitochondrial permeability transition pore ; MPTP ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Muscle contraction ; Myocardial Contraction - drug effects ; Myocardial Reperfusion Injury - complications ; Myocarditis. Cardiomyopathies ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - metabolism ; Oxidative stress ; Oxidative Stress - drug effects ; OXYGEN ; PERMEABILITY ; Proto-Oncogene Proteins c-akt - metabolism ; RATS ; Rats, Sprague-Dawley ; Reperfusion ; Reperfusion injury ; Toxicology ; Tumors ; Western blotting</subject><ispartof>Toxicology and applied pharmacology, 2013-04, Vol.268 (2), p.149-156</ispartof><rights>2012 Elsevier Inc.</rights><rights>2014 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c447t-674d7d1d1d5b8c69bc799b4e7fb10f1e13d70bcd5732e890dd2ff80fa9f46a283</citedby><cites>FETCH-LOGICAL-c447t-674d7d1d1d5b8c69bc799b4e7fb10f1e13d70bcd5732e890dd2ff80fa9f46a283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0041008X12005303$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27282912$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23262186$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22285270$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Gharanei, M.</creatorcontrib><creatorcontrib>Hussain, A.</creatorcontrib><creatorcontrib>Janneh, O.</creatorcontrib><creatorcontrib>Maddock, H.L.</creatorcontrib><title>Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocardial ischaemia reperfusion and the mechanistic basis of protection, in particular the role of the mitochondrial permeability transition pore (mPTP) in such protection. The effects of doxorubicin (1μM)±cyclosporine A (CsA, 0.2μM; inhibits mPTP) were investigated in isolated male Sprague–Dawley rats using Langendorff heart and papillary muscle contraction models subjected to simulated ischaemia and reperfusion injury. Isolated rat cardiac myocytes were used in an oxidative stress model to study the effects of drug treatment on mPTP by confocal microscopy. Western blot analysis evaluated the effects of drug treatment on p-Akt and p-Erk 1/2 levels. Langendorff and the isometric contraction models showed a detrimental effect of doxorubicin throughout reperfusion/reoxygenation as well as increased p-Akt and p-Erk levels. Interestingly, CsA not only reversed the detrimental effects of doxorubicin, but also reduced p-Akt and p-Erk levels. In the sustained oxidative stress assay to study mPTP opening, doxorubicin decreased the time taken to depolarization and hypercontracture, but these effects were delayed in the presence of CsA. Collectively, our data suggest for the first that doxorubicin exacerbates myocardial injury in an ischaemia reperfusion model. If the inhibition of mPTP ameliorates the cardiotoxic effects of doxorubicin, then more selective inhibitors of mPTP should be further investigated for their utility in patients receiving doxorubicin.
► Doxorubicin exacerbates myocardial ischaemia reperfusion injury. ► Co-treatment with CsA protects against doxorubicin induced myocardial injury. ► CsA delays doxorubicin induced mPTP opening in laser induced stress model. ► Doxorubicin causes increase in p-Akt and p-Erk levels during reperfusion injury. ► CsA or other mPTP inhibitors may be useful against drug-induced cardiotoxicity.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>ADENINES</subject><subject>Animals</subject><subject>ANOXIA</subject><subject>Anthracycline</subject><subject>Antibiotics, Antineoplastic - toxicity</subject><subject>APOPTOSIS</subject><subject>ATP</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Cardiac muscle</subject><subject>Cardiology. Vascular system</subject><subject>cardiomyocytes</subject><subject>Cell death</subject><subject>Chemotherapy</subject><subject>Confocal microscopy</subject><subject>Cyclophilin D</subject><subject>Cyclosporin A</subject><subject>CYCLOSPORINE</subject><subject>Data processing</subject><subject>DEPOLARIZATION</subject><subject>DOXORUBICIN</subject><subject>Doxorubicin - toxicity</subject><subject>Drugs</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>HEART</subject><subject>Hemodynamics - drug effects</subject><subject>Injuries</subject><subject>Ischaemia</subject><subject>Ischemia</subject><subject>Male</subject><subject>Medical sciences</subject><subject>MITOCHONDRIA</subject><subject>Mitochondrial Membrane Transport Proteins - drug effects</subject><subject>Mitochondrial permeability transition pore</subject><subject>MPTP</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Muscle contraction</subject><subject>Myocardial Contraction - drug effects</subject><subject>Myocardial Reperfusion Injury - complications</subject><subject>Myocarditis. Cardiomyopathies</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>OXYGEN</subject><subject>PERMEABILITY</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>RATS</subject><subject>Rats, Sprague-Dawley</subject><subject>Reperfusion</subject><subject>Reperfusion injury</subject><subject>Toxicology</subject><subject>Tumors</subject><subject>Western blotting</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcuqFDEQhoMonnH0BVxIQAQ3PVaSnr6AGzle4YAbBXchnVScDN1Jm6SPZx7CdzbNjLqTFASqvvqpqp-Qpwx2DFjz6rjLSs07DozvSgCIe2TDoG8qEELcJxuAmlUA3bcr8iilIwD0dc0ekisueMNZ12zIr7fhLsRlcNp56rxZNBo6nYJW0Tg1ltRxiSfqEsU7pTEOKhfAhnEMP53_Xgr6oHBymqYcMSV66xQNM_q1GCzNB6STy0EfgjdxVZwxTqgGN7p8ojkqn1x2wdM5RHxMHlg1Jnxy-bfk6_t3X64_VjefP3y6fnNT6bpuc9W0tWkNK28_dLrpB932_VBjawcGliETpoVBm30rOHY9GMOt7cCq3taN4p3Ykudn3ZCyk0m7jPqgg_eos-Scd3veQqFenqk5hh8Lpiynsi6Oo_IYliSZ4KJjXEBfUH5GdQwpRbRyjm5S8SQZyNUseZSrWXI1S5YoZpWmZxf9ZZjQ_G35404BXlwAlbQabTmWdukf1_KO92WALXl95rDc7NZhXFdCX6x0cd3IBPe_OX4DIUO2VA</recordid><startdate>20130415</startdate><enddate>20130415</enddate><creator>Gharanei, M.</creator><creator>Hussain, A.</creator><creator>Janneh, O.</creator><creator>Maddock, H.L.</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>7U7</scope><scope>C1K</scope><scope>OTOTI</scope></search><sort><creationdate>20130415</creationdate><title>Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore</title><author>Gharanei, M. ; Hussain, A. ; Janneh, O. ; Maddock, H.L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c447t-674d7d1d1d5b8c69bc799b4e7fb10f1e13d70bcd5732e890dd2ff80fa9f46a283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>ADENINES</topic><topic>Animals</topic><topic>ANOXIA</topic><topic>Anthracycline</topic><topic>Antibiotics, Antineoplastic - toxicity</topic><topic>APOPTOSIS</topic><topic>ATP</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Cardiac muscle</topic><topic>Cardiology. Vascular system</topic><topic>cardiomyocytes</topic><topic>Cell death</topic><topic>Chemotherapy</topic><topic>Confocal microscopy</topic><topic>Cyclophilin D</topic><topic>Cyclosporin A</topic><topic>CYCLOSPORINE</topic><topic>Data processing</topic><topic>DEPOLARIZATION</topic><topic>DOXORUBICIN</topic><topic>Doxorubicin - toxicity</topic><topic>Drugs</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>HEART</topic><topic>Hemodynamics - drug effects</topic><topic>Injuries</topic><topic>Ischaemia</topic><topic>Ischemia</topic><topic>Male</topic><topic>Medical sciences</topic><topic>MITOCHONDRIA</topic><topic>Mitochondrial Membrane Transport Proteins - drug effects</topic><topic>Mitochondrial permeability transition pore</topic><topic>MPTP</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Muscle contraction</topic><topic>Myocardial Contraction - drug effects</topic><topic>Myocardial Reperfusion Injury - complications</topic><topic>Myocarditis. Cardiomyopathies</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>OXYGEN</topic><topic>PERMEABILITY</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>RATS</topic><topic>Rats, Sprague-Dawley</topic><topic>Reperfusion</topic><topic>Reperfusion injury</topic><topic>Toxicology</topic><topic>Tumors</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gharanei, M.</creatorcontrib><creatorcontrib>Hussain, A.</creatorcontrib><creatorcontrib>Janneh, O.</creatorcontrib><creatorcontrib>Maddock, H.L.</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><collection>OSTI.GOV</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gharanei, M.</au><au>Hussain, A.</au><au>Janneh, O.</au><au>Maddock, H.L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2013-04-15</date><risdate>2013</risdate><volume>268</volume><issue>2</issue><spage>149</spage><epage>156</epage><pages>149-156</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><coden>TXAPA9</coden><abstract>Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocardial ischaemia reperfusion and the mechanistic basis of protection, in particular the role of the mitochondrial permeability transition pore (mPTP) in such protection. The effects of doxorubicin (1μM)±cyclosporine A (CsA, 0.2μM; inhibits mPTP) were investigated in isolated male Sprague–Dawley rats using Langendorff heart and papillary muscle contraction models subjected to simulated ischaemia and reperfusion injury. Isolated rat cardiac myocytes were used in an oxidative stress model to study the effects of drug treatment on mPTP by confocal microscopy. Western blot analysis evaluated the effects of drug treatment on p-Akt and p-Erk 1/2 levels. Langendorff and the isometric contraction models showed a detrimental effect of doxorubicin throughout reperfusion/reoxygenation as well as increased p-Akt and p-Erk levels. Interestingly, CsA not only reversed the detrimental effects of doxorubicin, but also reduced p-Akt and p-Erk levels. In the sustained oxidative stress assay to study mPTP opening, doxorubicin decreased the time taken to depolarization and hypercontracture, but these effects were delayed in the presence of CsA. Collectively, our data suggest for the first that doxorubicin exacerbates myocardial injury in an ischaemia reperfusion model. If the inhibition of mPTP ameliorates the cardiotoxic effects of doxorubicin, then more selective inhibitors of mPTP should be further investigated for their utility in patients receiving doxorubicin.
► Doxorubicin exacerbates myocardial ischaemia reperfusion injury. ► Co-treatment with CsA protects against doxorubicin induced myocardial injury. ► CsA delays doxorubicin induced mPTP opening in laser induced stress model. ► Doxorubicin causes increase in p-Akt and p-Erk levels during reperfusion injury. ► CsA or other mPTP inhibitors may be useful against drug-induced cardiotoxicity.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>23262186</pmid><doi>10.1016/j.taap.2012.12.003</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0041-008X |
| ispartof | Toxicology and applied pharmacology, 2013-04, Vol.268 (2), p.149-156 |
| issn | 0041-008X 1096-0333 |
| language | eng |
| recordid | cdi_osti_scitechconnect_22285270 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | 60 APPLIED LIFE SCIENCES ADENINES Animals ANOXIA Anthracycline Antibiotics, Antineoplastic - toxicity APOPTOSIS ATP Biological and medical sciences Cancer Cardiac muscle Cardiology. Vascular system cardiomyocytes Cell death Chemotherapy Confocal microscopy Cyclophilin D Cyclosporin A CYCLOSPORINE Data processing DEPOLARIZATION DOXORUBICIN Doxorubicin - toxicity Drugs Extracellular Signal-Regulated MAP Kinases - metabolism HEART Hemodynamics - drug effects Injuries Ischaemia Ischemia Male Medical sciences MITOCHONDRIA Mitochondrial Membrane Transport Proteins - drug effects Mitochondrial permeability transition pore MPTP Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Muscle contraction Myocardial Contraction - drug effects Myocardial Reperfusion Injury - complications Myocarditis. Cardiomyopathies Myocytes, Cardiac - drug effects Myocytes, Cardiac - metabolism Oxidative stress Oxidative Stress - drug effects OXYGEN PERMEABILITY Proto-Oncogene Proteins c-akt - metabolism RATS Rats, Sprague-Dawley Reperfusion Reperfusion injury Toxicology Tumors Western blotting |
| title | Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T05%3A36%3A21IST&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=Doxorubicin%20induced%20myocardial%20injury%20is%20exacerbated%20following%20ischaemic%20stress%20via%20opening%20of%20the%20mitochondrial%20permeability%20transition%20pore&rft.jtitle=Toxicology%20and%20applied%20pharmacology&rft.au=Gharanei,%20M.&rft.date=2013-04-15&rft.volume=268&rft.issue=2&rft.spage=149&rft.epage=156&rft.pages=149-156&rft.issn=0041-008X&rft.eissn=1096-0333&rft.coden=TXAPA9&rft_id=info:doi/10.1016/j.taap.2012.12.003&rft_dat=%3Cproquest_osti_%3E1323812309%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=1323812309&rft_id=info:pmid/23262186&rft_els_id=S0041008X12005303&rfr_iscdi=true |