Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats
Cardiac beta-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, and fibrosis rendering the heart vulnerable to malignant arrhythmias. We aimed to explore the anti-arrhythmic efficacy of the anti-oxidative and anti-inflammatory compounds, melatonin, and omega-3, an...
Gespeichert in:
| Veröffentlicht in: | Antioxidants 2020-06, Vol.9 (6), p.546, Article 546 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 6 |
| container_start_page | 546 |
| container_title | Antioxidants |
| container_volume | 9 |
| creator | Bacova, Barbara Szeiffova Viczenczova, Csilla Andelova, Katarina Sykora, Matus Chaudagar, Kiranj Barancik, Miroslav Adamcova, Michaela Knezl, Vladimir Benova, Tamara Egan Weismann, Peter Slezak, Jan Tribulova, Narcisa |
| description | Cardiac beta-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, and fibrosis rendering the heart vulnerable to malignant arrhythmias. We aimed to explore the anti-arrhythmic efficacy of the anti-oxidative and anti-inflammatory compounds, melatonin, and omega-3, and their mechanisms of actions in normotensive and hypertensive rats exposed to isoproterenol (ISO) induced beta-adrenergic overdrive. Eight-month-old, male SHR, and Wistar rats were injected during 7 days with ISO (cumulative dose, 118 mg/kg). ISO rats were either untreated or concomitantly treated with melatonin (10 mg/kg/day) or omega-3 (Omacor, 1.68 g/kg/day) until 60 days of ISO withdrawal and compared to non-ISO controls. Findings showed that both melatonin and omega-3 increased threshold current to induce ventricular fibrillation (VF) in ISO rats regardless of the strain. Prolonged treatment with these compounds resulted in significant suppression of ISO-induced extracellular matrix alterations, as indicated by reduced areas of diffuse fibrosis and decline of hydroxyproline, collagen-1, SMAD2/3, and TGF-beta 1 protein levels. Importantly, the highly pro-arrhythmic ISO-induced disordered cardiomyocyte distribution of electrical coupling protein, connexin-43 (Cx43), and its remodeling (lateralization) were significantly attenuated by melatonin and omega-3 in Wistar as well as SHR hearts. In parallel, both compounds prevented the post-ISO-related increase in Cx43 variant phosphorylated at serine 368 along with PKC epsilon, which are known to modulate Cx43 remodeling. Melatonin and omega-3 increased SOD1 or SOD2 protein levels in ISO-exposed rats of both strains. Altogether, the results indicate that anti-arrhythmic effects of melatonin and omega-3 might be attributed to the protection of myocardial Cx43 topology and suppression of fibrosis in the setting of oxidative stress induced by catecholamine overdrive in normotensive and hypertensive rats. |
| doi_str_mv | 10.3390/antiox9060546 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_journals_2417715899</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A642928500</galeid><doaj_id>oai_doaj_org_article_ed9866785dd4489aa9da97745bc31c33</doaj_id><sourcerecordid>A642928500</sourcerecordid><originalsourceid>FETCH-LOGICAL-c486t-dde87376adeb27dd53cb538c2e014c0f5c260e1271c1c2c78ef691aa0da9573e3</originalsourceid><addsrcrecordid>eNqNkk9v0zAYhyMEYmjsyN0SFyRU8N_YviBV1cYmDYbYOEeu_ab1SOxiu9v66fhquO0YjBO5JHKe3_Mm9q9pXhH8jjGN35tQfLzTuMWCt0-aFxTLdsI0JU__ej5ojnK-xvXShCmsnzcHjAqFuSIvmp_TqjApLTdlOXqLjvsebMko9ugTDKbE4AMywaGLERZmwtA0ATr34Ts4dOvLEn1JsdSEj2GX2URrkvNmQLM7ztBVXMUhLjY7xeV6tUqQ8z174ucpZp9RnTAzVbKMgxl9AHRZtlid8DmmsepD9jewU5xuVpB-L3w1Jb9snvVmyHB0fz9svp0cX81OJ-cXH89m0_OJ5aotE-dASSZb42BOpXOC2blgylLAhFvcC0tbDIRKYomlViroW02Mwc5oIRmww-Zs73XRXHer5EeTNl00vtstxLToTCreDtCB06ptpRLOca60MbpKpORibhmxjFXXh71rtZ6P4CyEkszwSPr4TfDLbhFvOsl4SxSvgjf3ghR_rCGXbvTZwjCYAHGdO8qJZIpSiiv6-h_0Oq5TqFu1oyQRSus_1MLUH_Chj3Wu3Uq7acuppkrgrWuyp2w9t5ygf_hkgrttH7tHfay82vO3MI99th6ChYdM7aMQTDAuttUkM1_MtkWzuA6lRt_-f5T9Agv09iU</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2417715899</pqid></control><display><type>article</type><title>Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats</title><source>DOAJ Directory of Open Access Journals</source><source>PubMed Central Open Access</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Bacova, Barbara Szeiffova ; Viczenczova, Csilla ; Andelova, Katarina ; Sykora, Matus ; Chaudagar, Kiranj ; Barancik, Miroslav ; Adamcova, Michaela ; Knezl, Vladimir ; Benova, Tamara Egan ; Weismann, Peter ; Slezak, Jan ; Tribulova, Narcisa</creator><creatorcontrib>Bacova, Barbara Szeiffova ; Viczenczova, Csilla ; Andelova, Katarina ; Sykora, Matus ; Chaudagar, Kiranj ; Barancik, Miroslav ; Adamcova, Michaela ; Knezl, Vladimir ; Benova, Tamara Egan ; Weismann, Peter ; Slezak, Jan ; Tribulova, Narcisa</creatorcontrib><description>Cardiac beta-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, and fibrosis rendering the heart vulnerable to malignant arrhythmias. We aimed to explore the anti-arrhythmic efficacy of the anti-oxidative and anti-inflammatory compounds, melatonin, and omega-3, and their mechanisms of actions in normotensive and hypertensive rats exposed to isoproterenol (ISO) induced beta-adrenergic overdrive. Eight-month-old, male SHR, and Wistar rats were injected during 7 days with ISO (cumulative dose, 118 mg/kg). ISO rats were either untreated or concomitantly treated with melatonin (10 mg/kg/day) or omega-3 (Omacor, 1.68 g/kg/day) until 60 days of ISO withdrawal and compared to non-ISO controls. Findings showed that both melatonin and omega-3 increased threshold current to induce ventricular fibrillation (VF) in ISO rats regardless of the strain. Prolonged treatment with these compounds resulted in significant suppression of ISO-induced extracellular matrix alterations, as indicated by reduced areas of diffuse fibrosis and decline of hydroxyproline, collagen-1, SMAD2/3, and TGF-beta 1 protein levels. Importantly, the highly pro-arrhythmic ISO-induced disordered cardiomyocyte distribution of electrical coupling protein, connexin-43 (Cx43), and its remodeling (lateralization) were significantly attenuated by melatonin and omega-3 in Wistar as well as SHR hearts. In parallel, both compounds prevented the post-ISO-related increase in Cx43 variant phosphorylated at serine 368 along with PKC epsilon, which are known to modulate Cx43 remodeling. Melatonin and omega-3 increased SOD1 or SOD2 protein levels in ISO-exposed rats of both strains. Altogether, the results indicate that anti-arrhythmic effects of melatonin and omega-3 might be attributed to the protection of myocardial Cx43 topology and suppression of fibrosis in the setting of oxidative stress induced by catecholamine overdrive in normotensive and hypertensive rats.</description><identifier>ISSN: 2076-3921</identifier><identifier>EISSN: 2076-3921</identifier><identifier>DOI: 10.3390/antiox9060546</identifier><identifier>PMID: 32580481</identifier><language>eng</language><publisher>BASEL: Mdpi</publisher><subject>Antiarrhythmics ; Biochemistry & Molecular Biology ; Cardiac arrhythmia ; Cardiomyocytes ; Catecholamines ; Chemistry, Medicinal ; Collagen ; Connexin 43 ; Drinking water ; Extracellular matrix ; Fibrillation ; Fibrosis ; Food Science & Technology ; Health aspects ; Heart ; Hydroxyproline ; Hypertension ; Hypertrophy ; Inflammation ; Ischemia ; Isoproterenol ; Laboratory animals ; Life Sciences & Biomedicine ; Melatonin ; Omega 3 fatty acids ; Ostomy ; Oxidation ; Oxidative stress ; Pharmacology & Pharmacy ; Prevention ; Protein kinase C ; Proteins ; rat heart ; Rodents ; Science & Technology ; Serine ; Smad2 protein ; Superoxide dismutase ; Transforming growth factor-b1 ; Ventricle ; ventricular fibrillation</subject><ispartof>Antioxidants, 2020-06, Vol.9 (6), p.546, Article 546</ispartof><rights>COPYRIGHT 2020 MDPI AG</rights><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>30</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000553534500001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c486t-dde87376adeb27dd53cb538c2e014c0f5c260e1271c1c2c78ef691aa0da9573e3</citedby><cites>FETCH-LOGICAL-c486t-dde87376adeb27dd53cb538c2e014c0f5c260e1271c1c2c78ef691aa0da9573e3</cites><orcidid>0000-0002-1499-7687 ; 0000-0002-0438-3956 ; 0000-0002-4217-4493 ; 0000-0002-5904-4249 ; 0000-0001-8394-7459</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346184/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346184/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2115,27928,27929,53795,53797</link.rule.ids></links><search><creatorcontrib>Bacova, Barbara Szeiffova</creatorcontrib><creatorcontrib>Viczenczova, Csilla</creatorcontrib><creatorcontrib>Andelova, Katarina</creatorcontrib><creatorcontrib>Sykora, Matus</creatorcontrib><creatorcontrib>Chaudagar, Kiranj</creatorcontrib><creatorcontrib>Barancik, Miroslav</creatorcontrib><creatorcontrib>Adamcova, Michaela</creatorcontrib><creatorcontrib>Knezl, Vladimir</creatorcontrib><creatorcontrib>Benova, Tamara Egan</creatorcontrib><creatorcontrib>Weismann, Peter</creatorcontrib><creatorcontrib>Slezak, Jan</creatorcontrib><creatorcontrib>Tribulova, Narcisa</creatorcontrib><title>Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats</title><title>Antioxidants</title><addtitle>ANTIOXIDANTS-BASEL</addtitle><description>Cardiac beta-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, and fibrosis rendering the heart vulnerable to malignant arrhythmias. We aimed to explore the anti-arrhythmic efficacy of the anti-oxidative and anti-inflammatory compounds, melatonin, and omega-3, and their mechanisms of actions in normotensive and hypertensive rats exposed to isoproterenol (ISO) induced beta-adrenergic overdrive. Eight-month-old, male SHR, and Wistar rats were injected during 7 days with ISO (cumulative dose, 118 mg/kg). ISO rats were either untreated or concomitantly treated with melatonin (10 mg/kg/day) or omega-3 (Omacor, 1.68 g/kg/day) until 60 days of ISO withdrawal and compared to non-ISO controls. Findings showed that both melatonin and omega-3 increased threshold current to induce ventricular fibrillation (VF) in ISO rats regardless of the strain. Prolonged treatment with these compounds resulted in significant suppression of ISO-induced extracellular matrix alterations, as indicated by reduced areas of diffuse fibrosis and decline of hydroxyproline, collagen-1, SMAD2/3, and TGF-beta 1 protein levels. Importantly, the highly pro-arrhythmic ISO-induced disordered cardiomyocyte distribution of electrical coupling protein, connexin-43 (Cx43), and its remodeling (lateralization) were significantly attenuated by melatonin and omega-3 in Wistar as well as SHR hearts. In parallel, both compounds prevented the post-ISO-related increase in Cx43 variant phosphorylated at serine 368 along with PKC epsilon, which are known to modulate Cx43 remodeling. Melatonin and omega-3 increased SOD1 or SOD2 protein levels in ISO-exposed rats of both strains. Altogether, the results indicate that anti-arrhythmic effects of melatonin and omega-3 might be attributed to the protection of myocardial Cx43 topology and suppression of fibrosis in the setting of oxidative stress induced by catecholamine overdrive in normotensive and hypertensive rats.</description><subject>Antiarrhythmics</subject><subject>Biochemistry & Molecular Biology</subject><subject>Cardiac arrhythmia</subject><subject>Cardiomyocytes</subject><subject>Catecholamines</subject><subject>Chemistry, Medicinal</subject><subject>Collagen</subject><subject>Connexin 43</subject><subject>Drinking water</subject><subject>Extracellular matrix</subject><subject>Fibrillation</subject><subject>Fibrosis</subject><subject>Food Science & Technology</subject><subject>Health aspects</subject><subject>Heart</subject><subject>Hydroxyproline</subject><subject>Hypertension</subject><subject>Hypertrophy</subject><subject>Inflammation</subject><subject>Ischemia</subject><subject>Isoproterenol</subject><subject>Laboratory animals</subject><subject>Life Sciences & Biomedicine</subject><subject>Melatonin</subject><subject>Omega 3 fatty acids</subject><subject>Ostomy</subject><subject>Oxidation</subject><subject>Oxidative stress</subject><subject>Pharmacology & Pharmacy</subject><subject>Prevention</subject><subject>Protein kinase C</subject><subject>Proteins</subject><subject>rat heart</subject><subject>Rodents</subject><subject>Science & Technology</subject><subject>Serine</subject><subject>Smad2 protein</subject><subject>Superoxide dismutase</subject><subject>Transforming growth factor-b1</subject><subject>Ventricle</subject><subject>ventricular fibrillation</subject><issn>2076-3921</issn><issn>2076-3921</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkk9v0zAYhyMEYmjsyN0SFyRU8N_YviBV1cYmDYbYOEeu_ab1SOxiu9v66fhquO0YjBO5JHKe3_Mm9q9pXhH8jjGN35tQfLzTuMWCt0-aFxTLdsI0JU__ej5ojnK-xvXShCmsnzcHjAqFuSIvmp_TqjApLTdlOXqLjvsebMko9ugTDKbE4AMywaGLERZmwtA0ATr34Ts4dOvLEn1JsdSEj2GX2URrkvNmQLM7ztBVXMUhLjY7xeV6tUqQ8z174ucpZp9RnTAzVbKMgxl9AHRZtlid8DmmsepD9jewU5xuVpB-L3w1Jb9snvVmyHB0fz9svp0cX81OJ-cXH89m0_OJ5aotE-dASSZb42BOpXOC2blgylLAhFvcC0tbDIRKYomlViroW02Mwc5oIRmww-Zs73XRXHer5EeTNl00vtstxLToTCreDtCB06ptpRLOca60MbpKpORibhmxjFXXh71rtZ6P4CyEkszwSPr4TfDLbhFvOsl4SxSvgjf3ghR_rCGXbvTZwjCYAHGdO8qJZIpSiiv6-h_0Oq5TqFu1oyQRSus_1MLUH_Chj3Wu3Uq7acuppkrgrWuyp2w9t5ygf_hkgrttH7tHfay82vO3MI99th6ChYdM7aMQTDAuttUkM1_MtkWzuA6lRt_-f5T9Agv09iU</recordid><startdate>20200601</startdate><enddate>20200601</enddate><creator>Bacova, Barbara Szeiffova</creator><creator>Viczenczova, Csilla</creator><creator>Andelova, Katarina</creator><creator>Sykora, Matus</creator><creator>Chaudagar, Kiranj</creator><creator>Barancik, Miroslav</creator><creator>Adamcova, Michaela</creator><creator>Knezl, Vladimir</creator><creator>Benova, Tamara Egan</creator><creator>Weismann, Peter</creator><creator>Slezak, Jan</creator><creator>Tribulova, Narcisa</creator><general>Mdpi</general><general>MDPI AG</general><general>MDPI</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QR</scope><scope>7T5</scope><scope>7TO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-1499-7687</orcidid><orcidid>https://orcid.org/0000-0002-0438-3956</orcidid><orcidid>https://orcid.org/0000-0002-4217-4493</orcidid><orcidid>https://orcid.org/0000-0002-5904-4249</orcidid><orcidid>https://orcid.org/0000-0001-8394-7459</orcidid></search><sort><creationdate>20200601</creationdate><title>Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats</title><author>Bacova, Barbara Szeiffova ; Viczenczova, Csilla ; Andelova, Katarina ; Sykora, Matus ; Chaudagar, Kiranj ; Barancik, Miroslav ; Adamcova, Michaela ; Knezl, Vladimir ; Benova, Tamara Egan ; Weismann, Peter ; Slezak, Jan ; Tribulova, Narcisa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-dde87376adeb27dd53cb538c2e014c0f5c260e1271c1c2c78ef691aa0da9573e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antiarrhythmics</topic><topic>Biochemistry & Molecular Biology</topic><topic>Cardiac arrhythmia</topic><topic>Cardiomyocytes</topic><topic>Catecholamines</topic><topic>Chemistry, Medicinal</topic><topic>Collagen</topic><topic>Connexin 43</topic><topic>Drinking water</topic><topic>Extracellular matrix</topic><topic>Fibrillation</topic><topic>Fibrosis</topic><topic>Food Science & Technology</topic><topic>Health aspects</topic><topic>Heart</topic><topic>Hydroxyproline</topic><topic>Hypertension</topic><topic>Hypertrophy</topic><topic>Inflammation</topic><topic>Ischemia</topic><topic>Isoproterenol</topic><topic>Laboratory animals</topic><topic>Life Sciences & Biomedicine</topic><topic>Melatonin</topic><topic>Omega 3 fatty acids</topic><topic>Ostomy</topic><topic>Oxidation</topic><topic>Oxidative stress</topic><topic>Pharmacology & Pharmacy</topic><topic>Prevention</topic><topic>Protein kinase C</topic><topic>Proteins</topic><topic>rat heart</topic><topic>Rodents</topic><topic>Science & Technology</topic><topic>Serine</topic><topic>Smad2 protein</topic><topic>Superoxide dismutase</topic><topic>Transforming growth factor-b1</topic><topic>Ventricle</topic><topic>ventricular fibrillation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bacova, Barbara Szeiffova</creatorcontrib><creatorcontrib>Viczenczova, Csilla</creatorcontrib><creatorcontrib>Andelova, Katarina</creatorcontrib><creatorcontrib>Sykora, Matus</creatorcontrib><creatorcontrib>Chaudagar, Kiranj</creatorcontrib><creatorcontrib>Barancik, Miroslav</creatorcontrib><creatorcontrib>Adamcova, Michaela</creatorcontrib><creatorcontrib>Knezl, Vladimir</creatorcontrib><creatorcontrib>Benova, Tamara Egan</creatorcontrib><creatorcontrib>Weismann, Peter</creatorcontrib><creatorcontrib>Slezak, Jan</creatorcontrib><creatorcontrib>Tribulova, Narcisa</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Access via ProQuest (Open Access)</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Antioxidants</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bacova, Barbara Szeiffova</au><au>Viczenczova, Csilla</au><au>Andelova, Katarina</au><au>Sykora, Matus</au><au>Chaudagar, Kiranj</au><au>Barancik, Miroslav</au><au>Adamcova, Michaela</au><au>Knezl, Vladimir</au><au>Benova, Tamara Egan</au><au>Weismann, Peter</au><au>Slezak, Jan</au><au>Tribulova, Narcisa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats</atitle><jtitle>Antioxidants</jtitle><stitle>ANTIOXIDANTS-BASEL</stitle><date>2020-06-01</date><risdate>2020</risdate><volume>9</volume><issue>6</issue><spage>546</spage><pages>546-</pages><artnum>546</artnum><issn>2076-3921</issn><eissn>2076-3921</eissn><abstract>Cardiac beta-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, and fibrosis rendering the heart vulnerable to malignant arrhythmias. We aimed to explore the anti-arrhythmic efficacy of the anti-oxidative and anti-inflammatory compounds, melatonin, and omega-3, and their mechanisms of actions in normotensive and hypertensive rats exposed to isoproterenol (ISO) induced beta-adrenergic overdrive. Eight-month-old, male SHR, and Wistar rats were injected during 7 days with ISO (cumulative dose, 118 mg/kg). ISO rats were either untreated or concomitantly treated with melatonin (10 mg/kg/day) or omega-3 (Omacor, 1.68 g/kg/day) until 60 days of ISO withdrawal and compared to non-ISO controls. Findings showed that both melatonin and omega-3 increased threshold current to induce ventricular fibrillation (VF) in ISO rats regardless of the strain. Prolonged treatment with these compounds resulted in significant suppression of ISO-induced extracellular matrix alterations, as indicated by reduced areas of diffuse fibrosis and decline of hydroxyproline, collagen-1, SMAD2/3, and TGF-beta 1 protein levels. Importantly, the highly pro-arrhythmic ISO-induced disordered cardiomyocyte distribution of electrical coupling protein, connexin-43 (Cx43), and its remodeling (lateralization) were significantly attenuated by melatonin and omega-3 in Wistar as well as SHR hearts. In parallel, both compounds prevented the post-ISO-related increase in Cx43 variant phosphorylated at serine 368 along with PKC epsilon, which are known to modulate Cx43 remodeling. Melatonin and omega-3 increased SOD1 or SOD2 protein levels in ISO-exposed rats of both strains. Altogether, the results indicate that anti-arrhythmic effects of melatonin and omega-3 might be attributed to the protection of myocardial Cx43 topology and suppression of fibrosis in the setting of oxidative stress induced by catecholamine overdrive in normotensive and hypertensive rats.</abstract><cop>BASEL</cop><pub>Mdpi</pub><pmid>32580481</pmid><doi>10.3390/antiox9060546</doi><tpages>19</tpages><orcidid>https://orcid.org/0000-0002-1499-7687</orcidid><orcidid>https://orcid.org/0000-0002-0438-3956</orcidid><orcidid>https://orcid.org/0000-0002-4217-4493</orcidid><orcidid>https://orcid.org/0000-0002-5904-4249</orcidid><orcidid>https://orcid.org/0000-0001-8394-7459</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2076-3921 |
| ispartof | Antioxidants, 2020-06, Vol.9 (6), p.546, Article 546 |
| issn | 2076-3921 2076-3921 |
| language | eng |
| recordid | cdi_proquest_journals_2417715899 |
| source | DOAJ Directory of Open Access Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Antiarrhythmics Biochemistry & Molecular Biology Cardiac arrhythmia Cardiomyocytes Catecholamines Chemistry, Medicinal Collagen Connexin 43 Drinking water Extracellular matrix Fibrillation Fibrosis Food Science & Technology Health aspects Heart Hydroxyproline Hypertension Hypertrophy Inflammation Ischemia Isoproterenol Laboratory animals Life Sciences & Biomedicine Melatonin Omega 3 fatty acids Ostomy Oxidation Oxidative stress Pharmacology & Pharmacy Prevention Protein kinase C Proteins rat heart Rodents Science & Technology Serine Smad2 protein Superoxide dismutase Transforming growth factor-b1 Ventricle ventricular fibrillation |
| title | Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T09%3A50%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Antiarrhythmic%20Effects%20of%20Melatonin%20and%20Omega-3%20Are%20Linked%20with%20Protection%20of%20Myocardial%20Cx43%20Topology%20and%20Suppression%20of%20Fibrosis%20in%20Catecholamine%20Stressed%20Normotensive%20and%20Hypertensive%20Rats&rft.jtitle=Antioxidants&rft.au=Bacova,%20Barbara%20Szeiffova&rft.date=2020-06-01&rft.volume=9&rft.issue=6&rft.spage=546&rft.pages=546-&rft.artnum=546&rft.issn=2076-3921&rft.eissn=2076-3921&rft_id=info:doi/10.3390/antiox9060546&rft_dat=%3Cgale_proqu%3EA642928500%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2417715899&rft_id=info:pmid/32580481&rft_galeid=A642928500&rft_doaj_id=oai_doaj_org_article_ed9866785dd4489aa9da97745bc31c33&rfr_iscdi=true |