Cardiotoxicity of environmental contaminant tributyltin involves myocyte oxidative stress and abnormal Ca 2+ handling
Tributyltin (TBT) is an organotin environmental pollutant widely used as an agricultural and wood biocide and in antifouling paints. Countries began restricting TBT use in the 2000s, but their use continues in some agroindustrial processes. We studied the acute effect of TBT on cardiac function by a...
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Veröffentlicht in: | Environmental pollution (1987) 2019-04, Vol.247, p.371 |
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creator | Pereira, C L V Ximenes, C F Merlo, E Sciortino, A S Monteiro, J S Moreira, A Jacobsen, B B Graceli, J B Ginsburg, K S Ribeiro Junior, R F Bers, D M Stefanon, I |
description | Tributyltin (TBT) is an organotin environmental pollutant widely used as an agricultural and wood biocide and in antifouling paints. Countries began restricting TBT use in the 2000s, but their use continues in some agroindustrial processes. We studied the acute effect of TBT on cardiac function by analyzing myocardial contractility and Ca
handling. Cardiac contractility was evaluated in isolated papillary muscle and whole heart upon TBT exposure. Isolated ventricular myocytes were used to measure calcium (Ca
) transients, sarcoplasmic reticulum (SR) Ca
content and SR Ca
leak (as Ca
sparks). Reactive oxygen species (ROS), as superoxide anion (O2
) was detected at intracellular and mitochondrial myocardium. TBT depressed cardiac contractility and relaxation in papillary muscle and intact whole heart. TBT increased cytosolic, mitochondrial ROS production and decreased mitochondrial membrane potential. In isolated cardiomyocytes TBT decreased both Ca
transients and SR Ca
content and increased diastolic SR Ca
leak. Decay of twitch and caffeine-induced Ca
transients were slowed by the presence of TBT. Dantrolene prevented and Tiron limited the reduction in SR Ca
content and transients. The environmental contaminant TBT causes cardiotoxicity within minutes, and may be considered hazardous to the mammalian heart. TBT acutely induced a negative inotropic effect in isolated papillary muscle and whole heart, increased arrhythmogenic SR Ca
leak leading to reduced SR Ca
content and reduced Ca
transients. TBT-induced myocardial ROS production, may destabilize the SR Ca
release channel RyR2 and reduce SR Ca
pump activity as key factors in the TBT-induced negative inotropic and lusitropic effects. |
doi_str_mv | 10.1016/j.envpol.2019.01.053 |
format | Article |
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handling. Cardiac contractility was evaluated in isolated papillary muscle and whole heart upon TBT exposure. Isolated ventricular myocytes were used to measure calcium (Ca
) transients, sarcoplasmic reticulum (SR) Ca
content and SR Ca
leak (as Ca
sparks). Reactive oxygen species (ROS), as superoxide anion (O2
) was detected at intracellular and mitochondrial myocardium. TBT depressed cardiac contractility and relaxation in papillary muscle and intact whole heart. TBT increased cytosolic, mitochondrial ROS production and decreased mitochondrial membrane potential. In isolated cardiomyocytes TBT decreased both Ca
transients and SR Ca
content and increased diastolic SR Ca
leak. Decay of twitch and caffeine-induced Ca
transients were slowed by the presence of TBT. Dantrolene prevented and Tiron limited the reduction in SR Ca
content and transients. The environmental contaminant TBT causes cardiotoxicity within minutes, and may be considered hazardous to the mammalian heart. TBT acutely induced a negative inotropic effect in isolated papillary muscle and whole heart, increased arrhythmogenic SR Ca
leak leading to reduced SR Ca
content and reduced Ca
transients. TBT-induced myocardial ROS production, may destabilize the SR Ca
release channel RyR2 and reduce SR Ca
pump activity as key factors in the TBT-induced negative inotropic and lusitropic effects.</description><identifier>EISSN: 1873-6424</identifier><identifier>DOI: 10.1016/j.envpol.2019.01.053</identifier><identifier>PMID: 30690233</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Calcium - metabolism ; Cardiotoxicity - metabolism ; Mitochondria - metabolism ; Myocardial Contraction ; Myocardium - metabolism ; Myocytes, Cardiac - drug effects ; Oxidative Stress - physiology ; Reactive Oxygen Species - metabolism ; Ryanodine Receptor Calcium Release Channel ; Sarcoplasmic Reticulum - metabolism ; Trialkyltin Compounds - toxicity ; Water Pollutants, Chemical - toxicity</subject><ispartof>Environmental pollution (1987), 2019-04, Vol.247, p.371</ispartof><rights>Copyright © 2019 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30690233$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pereira, C L V</creatorcontrib><creatorcontrib>Ximenes, C F</creatorcontrib><creatorcontrib>Merlo, E</creatorcontrib><creatorcontrib>Sciortino, A S</creatorcontrib><creatorcontrib>Monteiro, J S</creatorcontrib><creatorcontrib>Moreira, A</creatorcontrib><creatorcontrib>Jacobsen, B B</creatorcontrib><creatorcontrib>Graceli, J B</creatorcontrib><creatorcontrib>Ginsburg, K S</creatorcontrib><creatorcontrib>Ribeiro Junior, R F</creatorcontrib><creatorcontrib>Bers, D M</creatorcontrib><creatorcontrib>Stefanon, I</creatorcontrib><title>Cardiotoxicity of environmental contaminant tributyltin involves myocyte oxidative stress and abnormal Ca 2+ handling</title><title>Environmental pollution (1987)</title><addtitle>Environ Pollut</addtitle><description>Tributyltin (TBT) is an organotin environmental pollutant widely used as an agricultural and wood biocide and in antifouling paints. Countries began restricting TBT use in the 2000s, but their use continues in some agroindustrial processes. We studied the acute effect of TBT on cardiac function by analyzing myocardial contractility and Ca
handling. Cardiac contractility was evaluated in isolated papillary muscle and whole heart upon TBT exposure. Isolated ventricular myocytes were used to measure calcium (Ca
) transients, sarcoplasmic reticulum (SR) Ca
content and SR Ca
leak (as Ca
sparks). Reactive oxygen species (ROS), as superoxide anion (O2
) was detected at intracellular and mitochondrial myocardium. TBT depressed cardiac contractility and relaxation in papillary muscle and intact whole heart. TBT increased cytosolic, mitochondrial ROS production and decreased mitochondrial membrane potential. In isolated cardiomyocytes TBT decreased both Ca
transients and SR Ca
content and increased diastolic SR Ca
leak. Decay of twitch and caffeine-induced Ca
transients were slowed by the presence of TBT. Dantrolene prevented and Tiron limited the reduction in SR Ca
content and transients. The environmental contaminant TBT causes cardiotoxicity within minutes, and may be considered hazardous to the mammalian heart. TBT acutely induced a negative inotropic effect in isolated papillary muscle and whole heart, increased arrhythmogenic SR Ca
leak leading to reduced SR Ca
content and reduced Ca
transients. TBT-induced myocardial ROS production, may destabilize the SR Ca
release channel RyR2 and reduce SR Ca
pump activity as key factors in the TBT-induced negative inotropic and lusitropic effects.</description><subject>Animals</subject><subject>Calcium - metabolism</subject><subject>Cardiotoxicity - metabolism</subject><subject>Mitochondria - metabolism</subject><subject>Myocardial Contraction</subject><subject>Myocardium - metabolism</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Oxidative Stress - physiology</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Ryanodine Receptor Calcium Release Channel</subject><subject>Sarcoplasmic Reticulum - metabolism</subject><subject>Trialkyltin Compounds - toxicity</subject><subject>Water Pollutants, Chemical - toxicity</subject><issn>1873-6424</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFjs1KxDAURoMgzvjzBiJ3LxNvmlqddVF8gNkPaZvROyQ3JUmLeXuz0LWrA4ePwyfEvUKpUHVPZ2l5nYOTDaq9RCXxWV-IrXp90buubdqNuE7pjIit1vpKbDR2e2y03oqlN3GikMM3jZQLhBPUFMXA3nI2DsZQ4YkNZ8iRhiUXl4mBeA1utQl8CWPJFmphMplWCylHmxIYnsAMHKKvmd5A8whf1Tniz1txeTIu2btf3oiH97dD_7Gbl8Hb6ThH8iaW499P_e_gB4ujUpI</recordid><startdate>201904</startdate><enddate>201904</enddate><creator>Pereira, C L V</creator><creator>Ximenes, C F</creator><creator>Merlo, E</creator><creator>Sciortino, A S</creator><creator>Monteiro, J S</creator><creator>Moreira, A</creator><creator>Jacobsen, B B</creator><creator>Graceli, J B</creator><creator>Ginsburg, K S</creator><creator>Ribeiro Junior, R F</creator><creator>Bers, D M</creator><creator>Stefanon, I</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>201904</creationdate><title>Cardiotoxicity of environmental contaminant tributyltin involves myocyte oxidative stress and abnormal Ca 2+ handling</title><author>Pereira, C L V ; Ximenes, C F ; Merlo, E ; Sciortino, A S ; Monteiro, J S ; Moreira, A ; Jacobsen, B B ; Graceli, J B ; Ginsburg, K S ; Ribeiro Junior, R F ; Bers, D M ; Stefanon, I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_306902333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Calcium - metabolism</topic><topic>Cardiotoxicity - metabolism</topic><topic>Mitochondria - metabolism</topic><topic>Myocardial Contraction</topic><topic>Myocardium - metabolism</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Oxidative Stress - physiology</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Ryanodine Receptor Calcium Release Channel</topic><topic>Sarcoplasmic Reticulum - metabolism</topic><topic>Trialkyltin Compounds - toxicity</topic><topic>Water Pollutants, Chemical - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pereira, C L V</creatorcontrib><creatorcontrib>Ximenes, C F</creatorcontrib><creatorcontrib>Merlo, E</creatorcontrib><creatorcontrib>Sciortino, A S</creatorcontrib><creatorcontrib>Monteiro, J S</creatorcontrib><creatorcontrib>Moreira, A</creatorcontrib><creatorcontrib>Jacobsen, B B</creatorcontrib><creatorcontrib>Graceli, J B</creatorcontrib><creatorcontrib>Ginsburg, K S</creatorcontrib><creatorcontrib>Ribeiro Junior, R F</creatorcontrib><creatorcontrib>Bers, D M</creatorcontrib><creatorcontrib>Stefanon, I</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Environmental pollution (1987)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pereira, C L V</au><au>Ximenes, C F</au><au>Merlo, E</au><au>Sciortino, A S</au><au>Monteiro, J S</au><au>Moreira, A</au><au>Jacobsen, B B</au><au>Graceli, J B</au><au>Ginsburg, K S</au><au>Ribeiro Junior, R F</au><au>Bers, D M</au><au>Stefanon, I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cardiotoxicity of environmental contaminant tributyltin involves myocyte oxidative stress and abnormal Ca 2+ handling</atitle><jtitle>Environmental pollution (1987)</jtitle><addtitle>Environ Pollut</addtitle><date>2019-04</date><risdate>2019</risdate><volume>247</volume><spage>371</spage><pages>371-</pages><eissn>1873-6424</eissn><abstract>Tributyltin (TBT) is an organotin environmental pollutant widely used as an agricultural and wood biocide and in antifouling paints. Countries began restricting TBT use in the 2000s, but their use continues in some agroindustrial processes. We studied the acute effect of TBT on cardiac function by analyzing myocardial contractility and Ca
handling. Cardiac contractility was evaluated in isolated papillary muscle and whole heart upon TBT exposure. Isolated ventricular myocytes were used to measure calcium (Ca
) transients, sarcoplasmic reticulum (SR) Ca
content and SR Ca
leak (as Ca
sparks). Reactive oxygen species (ROS), as superoxide anion (O2
) was detected at intracellular and mitochondrial myocardium. TBT depressed cardiac contractility and relaxation in papillary muscle and intact whole heart. TBT increased cytosolic, mitochondrial ROS production and decreased mitochondrial membrane potential. In isolated cardiomyocytes TBT decreased both Ca
transients and SR Ca
content and increased diastolic SR Ca
leak. Decay of twitch and caffeine-induced Ca
transients were slowed by the presence of TBT. Dantrolene prevented and Tiron limited the reduction in SR Ca
content and transients. The environmental contaminant TBT causes cardiotoxicity within minutes, and may be considered hazardous to the mammalian heart. TBT acutely induced a negative inotropic effect in isolated papillary muscle and whole heart, increased arrhythmogenic SR Ca
leak leading to reduced SR Ca
content and reduced Ca
transients. TBT-induced myocardial ROS production, may destabilize the SR Ca
release channel RyR2 and reduce SR Ca
pump activity as key factors in the TBT-induced negative inotropic and lusitropic effects.</abstract><cop>England</cop><pmid>30690233</pmid><doi>10.1016/j.envpol.2019.01.053</doi></addata></record> |
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source | MEDLINE; Elsevier ScienceDirect Journals |
subjects | Animals Calcium - metabolism Cardiotoxicity - metabolism Mitochondria - metabolism Myocardial Contraction Myocardium - metabolism Myocytes, Cardiac - drug effects Oxidative Stress - physiology Reactive Oxygen Species - metabolism Ryanodine Receptor Calcium Release Channel Sarcoplasmic Reticulum - metabolism Trialkyltin Compounds - toxicity Water Pollutants, Chemical - toxicity |
title | Cardiotoxicity of environmental contaminant tributyltin involves myocyte oxidative stress and abnormal Ca 2+ handling |
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