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Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis: a new therapeutic implication
Ritonavir is a HIV protease inhibitor. In addition to its antiviral effect, Ritonavir directly inhibits the insulin-regulated glucose transporter GLUT4 and blocks glucose entry into fat and muscle cells. However, the effect of Ritonavir on cardiac GLUT4 inhibition during myocardial necrosis is not i...
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| Published in: | Journal of translational medicine 2013-03, Vol.11 (1), p.80-80, Article 80 |
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| creator | Gupta, Prachi Kanwal, Abhinav Putcha, Uday Kumar Bulani, Yogesh Sojitra, Bhavesh Khatua, Tarak Nath Kuncha, Madhusudana Banerjee, Sanjay Kumar |
| description | Ritonavir is a HIV protease inhibitor. In addition to its antiviral effect, Ritonavir directly inhibits the insulin-regulated glucose transporter GLUT4 and blocks glucose entry into fat and muscle cells. However, the effect of Ritonavir on cardiac GLUT4 inhibition during myocardial necrosis is not investigated. In the present study, we evaluated the role of Ritonavir in isoproterenol-induced myocardial necrosis in vivo and compared the effect with Phlorizin, a nonslective SGLTs inhibitor.
Isoproterenol (ISO) (150 mg/kg/day, i.p for 2 consecutive days) was administered to mice to cause myocardial necrosis. Phlorizin (400 mg/kg/day i.p twice daily for 2 days) and Ritonavir (10 mg/kg/day i.p twice daily for 2 days) were administered in two different groups of mice before isoproterenol administration.
Isoproterenol (ISO) (150 mg/kg/day, i.p for 2 consecutive days) administration caused significant (p |
| doi_str_mv | 10.1186/1479-5876-11-80 |
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Isoproterenol (ISO) (150 mg/kg/day, i.p for 2 consecutive days) was administered to mice to cause myocardial necrosis. Phlorizin (400 mg/kg/day i.p twice daily for 2 days) and Ritonavir (10 mg/kg/day i.p twice daily for 2 days) were administered in two different groups of mice before isoproterenol administration.
Isoproterenol (ISO) (150 mg/kg/day, i.p for 2 consecutive days) administration caused significant (p < 0.05) increase in heart/body weight ratio, and myocardial necrosis as evident by significant (p < 0.05) increase in serum markers i.e. SGOT and CK; and cardiac histopathological changes. Significant (p < 0.05) reduction in myocardial SOD and catalase activities, and GSH level along with a significant (p < 0.05) rise in myocardial TBARS and nitric oxide levels were observed after ISO administration. However, administration of phlorizin, a SGLT1 inhibitor has been found to exhibit partial protection in ISO induced myocardial necrosis, as observed by significant decrease in heart/body weight ratio and myocardial nitric oxide level; significant increase in myocardial SOD and catalase activities along with no histopathological alterations. On the other hand, administration of ritonavir, a nonspecific GLUT inhibitor has been found to exhibit complete protection as observed by normalisation of heart/body weight ratio, serum markers, antioxidant enzymes activities and histopathological alterations. In vitro study with heart homogenate confirmed no antioxidant effect of ritonavir and phlorizin in the absence and presence of isoproterenol.
Our study concluded that ritonavir, a nonspecific GLUT inhibitors showed complete protection in catecholamine induced myocardial necrosis.</description><identifier>ISSN: 1479-5876</identifier><identifier>EISSN: 1479-5876</identifier><identifier>DOI: 10.1186/1479-5876-11-80</identifier><identifier>PMID: 23531330</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Animals ; Antioxidants ; Antioxidants - metabolism ; Antioxidants - pharmacology ; Body Weight ; Cardiomyopathies - chemically induced ; Cardiomyopathies - drug therapy ; Cardiotonic Agents - therapeutic use ; Cardiovascular diseases ; Comparative analysis ; Complications and side effects ; Dextrose ; Dosage and administration ; Drug therapy ; Glucose ; Glucose Transporter Type 4 - metabolism ; Health aspects ; Heart attack ; Heart attacks ; Human immunodeficiency virus ; Industrial research ; Isoproterenol - adverse effects ; Male ; Mice ; Necrosis ; Necrosis - chemically induced ; Necrosis - drug therapy ; Nitric oxide ; Nitric Oxide - metabolism ; Nutrition ; Oxidative Stress ; Patient outcomes ; Pharmacology ; Phlorhizin - pharmacology ; Proteases ; Risk factors ; Ritonavir ; Ritonavir - therapeutic use ; Rodents ; Statistical analysis ; Studies ; Thiobarbituric Acid Reactive Substances - metabolism</subject><ispartof>Journal of translational medicine, 2013-03, Vol.11 (1), p.80-80, Article 80</ispartof><rights>COPYRIGHT 2013 BioMed Central Ltd.</rights><rights>2013 Gupta et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2013 Gupta et al.; licensee BioMed Central Ltd. 2013 Gupta et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b646t-5f2706ce262aa22432772f47d41dcfe41d9f56e0d4a6ad6a65b99e8647a393e43</citedby><cites>FETCH-LOGICAL-b646t-5f2706ce262aa22432772f47d41dcfe41d9f56e0d4a6ad6a65b99e8647a393e43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623744/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1326316482?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23531330$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gupta, Prachi</creatorcontrib><creatorcontrib>Kanwal, Abhinav</creatorcontrib><creatorcontrib>Putcha, Uday Kumar</creatorcontrib><creatorcontrib>Bulani, Yogesh</creatorcontrib><creatorcontrib>Sojitra, Bhavesh</creatorcontrib><creatorcontrib>Khatua, Tarak Nath</creatorcontrib><creatorcontrib>Kuncha, Madhusudana</creatorcontrib><creatorcontrib>Banerjee, Sanjay Kumar</creatorcontrib><title>Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis: a new therapeutic implication</title><title>Journal of translational medicine</title><addtitle>J Transl Med</addtitle><description>Ritonavir is a HIV protease inhibitor. In addition to its antiviral effect, Ritonavir directly inhibits the insulin-regulated glucose transporter GLUT4 and blocks glucose entry into fat and muscle cells. However, the effect of Ritonavir on cardiac GLUT4 inhibition during myocardial necrosis is not investigated. In the present study, we evaluated the role of Ritonavir in isoproterenol-induced myocardial necrosis in vivo and compared the effect with Phlorizin, a nonslective SGLTs inhibitor.
Isoproterenol (ISO) (150 mg/kg/day, i.p for 2 consecutive days) was administered to mice to cause myocardial necrosis. Phlorizin (400 mg/kg/day i.p twice daily for 2 days) and Ritonavir (10 mg/kg/day i.p twice daily for 2 days) were administered in two different groups of mice before isoproterenol administration.
Isoproterenol (ISO) (150 mg/kg/day, i.p for 2 consecutive days) administration caused significant (p < 0.05) increase in heart/body weight ratio, and myocardial necrosis as evident by significant (p < 0.05) increase in serum markers i.e. SGOT and CK; and cardiac histopathological changes. Significant (p < 0.05) reduction in myocardial SOD and catalase activities, and GSH level along with a significant (p < 0.05) rise in myocardial TBARS and nitric oxide levels were observed after ISO administration. However, administration of phlorizin, a SGLT1 inhibitor has been found to exhibit partial protection in ISO induced myocardial necrosis, as observed by significant decrease in heart/body weight ratio and myocardial nitric oxide level; significant increase in myocardial SOD and catalase activities along with no histopathological alterations. On the other hand, administration of ritonavir, a nonspecific GLUT inhibitor has been found to exhibit complete protection as observed by normalisation of heart/body weight ratio, serum markers, antioxidant enzymes activities and histopathological alterations. In vitro study with heart homogenate confirmed no antioxidant effect of ritonavir and phlorizin in the absence and presence of isoproterenol.
Our study concluded that ritonavir, a nonspecific GLUT inhibitors showed complete protection in catecholamine induced myocardial necrosis.</description><subject>Animals</subject><subject>Antioxidants</subject><subject>Antioxidants - metabolism</subject><subject>Antioxidants - pharmacology</subject><subject>Body Weight</subject><subject>Cardiomyopathies - chemically induced</subject><subject>Cardiomyopathies - drug therapy</subject><subject>Cardiotonic Agents - therapeutic use</subject><subject>Cardiovascular diseases</subject><subject>Comparative analysis</subject><subject>Complications and side effects</subject><subject>Dextrose</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Glucose</subject><subject>Glucose Transporter Type 4 - metabolism</subject><subject>Health aspects</subject><subject>Heart attack</subject><subject>Heart attacks</subject><subject>Human immunodeficiency virus</subject><subject>Industrial research</subject><subject>Isoproterenol - adverse effects</subject><subject>Male</subject><subject>Mice</subject><subject>Necrosis</subject><subject>Necrosis - chemically induced</subject><subject>Necrosis - drug therapy</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Nutrition</subject><subject>Oxidative Stress</subject><subject>Patient outcomes</subject><subject>Pharmacology</subject><subject>Phlorhizin - pharmacology</subject><subject>Proteases</subject><subject>Risk factors</subject><subject>Ritonavir</subject><subject>Ritonavir - therapeutic use</subject><subject>Rodents</subject><subject>Statistical analysis</subject><subject>Studies</subject><subject>Thiobarbituric Acid Reactive Substances - metabolism</subject><issn>1479-5876</issn><issn>1479-5876</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNp1kk1v1DAQhiMEoqVw5oYsceHQtP6KnXBAald8SZW4wNny2uOtq8QOdrKod354HW1ZuqjIlj2aeea1x-Oqek3wGSGtOCdcdnXTSlETUrf4SXW89zx9YB9VL3K-wZjyhnfPqyPKGkYYw8fV75VO1scxxQnM5LeAwLlioehQ8lMMeuvTKdKhzBL2SffIpnlzinxAPu8SE4TYF4edDVg03EaziBYygEkx-_we6WL_QtM1JD3CPHmD_DD23ujJx_CyeuZ0n-HV_X5S_fj08fvqS3317fPX1cVVvRZcTHXjqMTCABVUa0o5o1JSx6XlxBoHZe1cIwBbroW2Qotm3XXQCi416xhwdlJ92OmO83oAayBMpR41Jj_odKui9uowEvy12sStYoIyyReBy53A2sf_CBxGTBzU0gW1dEERolpcRN7d3yLFnzPkSQ0-G-h7HSDOWREmJG_LaV1B3_6D3sQ5hfJGhaKCEcFb-pfa6B6UDy6Ws80iqi4axoXsMGWFOnuEKsPC4E0M4HzxHySc7xKWHuYEbl8nwWr5fY9U9ubh--75P9-N3QGkP9dL</recordid><startdate>20130326</startdate><enddate>20130326</enddate><creator>Gupta, Prachi</creator><creator>Kanwal, Abhinav</creator><creator>Putcha, Uday Kumar</creator><creator>Bulani, Yogesh</creator><creator>Sojitra, Bhavesh</creator><creator>Khatua, Tarak Nath</creator><creator>Kuncha, Madhusudana</creator><creator>Banerjee, Sanjay Kumar</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><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>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7QO</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20130326</creationdate><title>Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis: a new therapeutic implication</title><author>Gupta, Prachi ; Kanwal, Abhinav ; Putcha, Uday Kumar ; Bulani, Yogesh ; Sojitra, Bhavesh ; Khatua, Tarak Nath ; Kuncha, Madhusudana ; Banerjee, Sanjay Kumar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b646t-5f2706ce262aa22432772f47d41dcfe41d9f56e0d4a6ad6a65b99e8647a393e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Antioxidants</topic><topic>Antioxidants - metabolism</topic><topic>Antioxidants - pharmacology</topic><topic>Body Weight</topic><topic>Cardiomyopathies - chemically induced</topic><topic>Cardiomyopathies - drug therapy</topic><topic>Cardiotonic Agents - therapeutic use</topic><topic>Cardiovascular diseases</topic><topic>Comparative analysis</topic><topic>Complications and side effects</topic><topic>Dextrose</topic><topic>Dosage and administration</topic><topic>Drug therapy</topic><topic>Glucose</topic><topic>Glucose Transporter Type 4 - metabolism</topic><topic>Health aspects</topic><topic>Heart attack</topic><topic>Heart attacks</topic><topic>Human immunodeficiency virus</topic><topic>Industrial research</topic><topic>Isoproterenol - adverse effects</topic><topic>Male</topic><topic>Mice</topic><topic>Necrosis</topic><topic>Necrosis - chemically induced</topic><topic>Necrosis - drug therapy</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>Nutrition</topic><topic>Oxidative Stress</topic><topic>Patient outcomes</topic><topic>Pharmacology</topic><topic>Phlorhizin - pharmacology</topic><topic>Proteases</topic><topic>Risk factors</topic><topic>Ritonavir</topic><topic>Ritonavir - therapeutic use</topic><topic>Rodents</topic><topic>Statistical analysis</topic><topic>Studies</topic><topic>Thiobarbituric Acid Reactive Substances - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gupta, Prachi</creatorcontrib><creatorcontrib>Kanwal, Abhinav</creatorcontrib><creatorcontrib>Putcha, Uday Kumar</creatorcontrib><creatorcontrib>Bulani, Yogesh</creatorcontrib><creatorcontrib>Sojitra, Bhavesh</creatorcontrib><creatorcontrib>Khatua, Tarak Nath</creatorcontrib><creatorcontrib>Kuncha, Madhusudana</creatorcontrib><creatorcontrib>Banerjee, Sanjay Kumar</creatorcontrib><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>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 Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</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>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</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>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of translational medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gupta, Prachi</au><au>Kanwal, Abhinav</au><au>Putcha, Uday Kumar</au><au>Bulani, Yogesh</au><au>Sojitra, Bhavesh</au><au>Khatua, Tarak Nath</au><au>Kuncha, Madhusudana</au><au>Banerjee, Sanjay Kumar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis: a new therapeutic implication</atitle><jtitle>Journal of translational medicine</jtitle><addtitle>J Transl Med</addtitle><date>2013-03-26</date><risdate>2013</risdate><volume>11</volume><issue>1</issue><spage>80</spage><epage>80</epage><pages>80-80</pages><artnum>80</artnum><issn>1479-5876</issn><eissn>1479-5876</eissn><abstract>Ritonavir is a HIV protease inhibitor. In addition to its antiviral effect, Ritonavir directly inhibits the insulin-regulated glucose transporter GLUT4 and blocks glucose entry into fat and muscle cells. However, the effect of Ritonavir on cardiac GLUT4 inhibition during myocardial necrosis is not investigated. In the present study, we evaluated the role of Ritonavir in isoproterenol-induced myocardial necrosis in vivo and compared the effect with Phlorizin, a nonslective SGLTs inhibitor.
Isoproterenol (ISO) (150 mg/kg/day, i.p for 2 consecutive days) was administered to mice to cause myocardial necrosis. Phlorizin (400 mg/kg/day i.p twice daily for 2 days) and Ritonavir (10 mg/kg/day i.p twice daily for 2 days) were administered in two different groups of mice before isoproterenol administration.
Isoproterenol (ISO) (150 mg/kg/day, i.p for 2 consecutive days) administration caused significant (p < 0.05) increase in heart/body weight ratio, and myocardial necrosis as evident by significant (p < 0.05) increase in serum markers i.e. SGOT and CK; and cardiac histopathological changes. Significant (p < 0.05) reduction in myocardial SOD and catalase activities, and GSH level along with a significant (p < 0.05) rise in myocardial TBARS and nitric oxide levels were observed after ISO administration. However, administration of phlorizin, a SGLT1 inhibitor has been found to exhibit partial protection in ISO induced myocardial necrosis, as observed by significant decrease in heart/body weight ratio and myocardial nitric oxide level; significant increase in myocardial SOD and catalase activities along with no histopathological alterations. On the other hand, administration of ritonavir, a nonspecific GLUT inhibitor has been found to exhibit complete protection as observed by normalisation of heart/body weight ratio, serum markers, antioxidant enzymes activities and histopathological alterations. In vitro study with heart homogenate confirmed no antioxidant effect of ritonavir and phlorizin in the absence and presence of isoproterenol.
Our study concluded that ritonavir, a nonspecific GLUT inhibitors showed complete protection in catecholamine induced myocardial necrosis.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>23531330</pmid><doi>10.1186/1479-5876-11-80</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of translational medicine, 2013-03, Vol.11 (1), p.80-80, Article 80 |
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| subjects | Animals Antioxidants Antioxidants - metabolism Antioxidants - pharmacology Body Weight Cardiomyopathies - chemically induced Cardiomyopathies - drug therapy Cardiotonic Agents - therapeutic use Cardiovascular diseases Comparative analysis Complications and side effects Dextrose Dosage and administration Drug therapy Glucose Glucose Transporter Type 4 - metabolism Health aspects Heart attack Heart attacks Human immunodeficiency virus Industrial research Isoproterenol - adverse effects Male Mice Necrosis Necrosis - chemically induced Necrosis - drug therapy Nitric oxide Nitric Oxide - metabolism Nutrition Oxidative Stress Patient outcomes Pharmacology Phlorhizin - pharmacology Proteases Risk factors Ritonavir Ritonavir - therapeutic use Rodents Statistical analysis Studies Thiobarbituric Acid Reactive Substances - metabolism |
| title | Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis: a new therapeutic implication |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T05%3A50%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cardioprotective%20effect%20of%20ritonavir,%20an%20antiviral%20drug,%20in%20isoproterenol%20induced%20myocardial%20necrosis:%20a%20new%20therapeutic%20implication&rft.jtitle=Journal%20of%20translational%20medicine&rft.au=Gupta,%20Prachi&rft.date=2013-03-26&rft.volume=11&rft.issue=1&rft.spage=80&rft.epage=80&rft.pages=80-80&rft.artnum=80&rft.issn=1479-5876&rft.eissn=1479-5876&rft_id=info:doi/10.1186/1479-5876-11-80&rft_dat=%3Cgale_pubme%3EA534679023%3C/gale_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-b646t-5f2706ce262aa22432772f47d41dcfe41d9f56e0d4a6ad6a65b99e8647a393e43%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1326316482&rft_id=info:pmid/23531330&rft_galeid=A534679023&rfr_iscdi=true |