Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1159/000452558 http://hdl.handle.net/11449/178450 |
Resumo: | Background: Cardiotoxicity is the major side effect of doxorubicin. As mechanisms that are involved in cardiotoxicity are ambiguous, new methods for attenuating cardiotoxicity are needed. Recent studies have shown that bisphosphonates can decrease oxidative stress. Therefore, the objective of this study was to evaluate the effect of pamidronate on preventing acute doxorubicin-induced cardiotoxicity. Methods: Sixty-four male Wistar rats were allocated into four groups: the control group (C), the pamidronate group (P), the doxorubicin group (D) and the doxorubicin/pamidronate group (DP). The rats in the P and DP groups received pamidronate injections (3 mg/kg, IP). After 24 hours, the rats in the D and DP groups received doxorubicin injections (20 mg/kg, IP). Forty-eight hours after doxorubicin injection, the rats were killed. Echocardiography, isolated heart study and biochemical analysis were performed. Results: Doxorubicin-induced acute cardiotoxicity showed increased matrix metalloproteinases (MMP)-2 activation, oxidative damage and induced alterations in myocardial energetic metabolism. Pamidronate did not inhibit MMP-2 activation but attenuated oxidative stress and improved myocardial energetic metabolism. Regarding cardiac function, the DP group exhibited a decrease in the left ventricular ejection fraction in the echocardiography and a decrease in +dP/dt in the isolated heart study compared with other groups. The same DP group presented serum hypocalcaemia. Conclusions: Despite its ability to reduce oxidative stress and improve energy metabolism in the heart, pamidronate worsened systolic function in rats treated with doxorubicin, and therefore we cannot recommend its use in conjunction with anthracycline chemotherapy. |
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Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in RatsHypocalcaemiaIsolated heart studyLeft ventricular dysfunctionMatrix metalloproteinaseBackground: Cardiotoxicity is the major side effect of doxorubicin. As mechanisms that are involved in cardiotoxicity are ambiguous, new methods for attenuating cardiotoxicity are needed. Recent studies have shown that bisphosphonates can decrease oxidative stress. Therefore, the objective of this study was to evaluate the effect of pamidronate on preventing acute doxorubicin-induced cardiotoxicity. Methods: Sixty-four male Wistar rats were allocated into four groups: the control group (C), the pamidronate group (P), the doxorubicin group (D) and the doxorubicin/pamidronate group (DP). The rats in the P and DP groups received pamidronate injections (3 mg/kg, IP). After 24 hours, the rats in the D and DP groups received doxorubicin injections (20 mg/kg, IP). Forty-eight hours after doxorubicin injection, the rats were killed. Echocardiography, isolated heart study and biochemical analysis were performed. Results: Doxorubicin-induced acute cardiotoxicity showed increased matrix metalloproteinases (MMP)-2 activation, oxidative damage and induced alterations in myocardial energetic metabolism. Pamidronate did not inhibit MMP-2 activation but attenuated oxidative stress and improved myocardial energetic metabolism. Regarding cardiac function, the DP group exhibited a decrease in the left ventricular ejection fraction in the echocardiography and a decrease in +dP/dt in the isolated heart study compared with other groups. The same DP group presented serum hypocalcaemia. Conclusions: Despite its ability to reduce oxidative stress and improve energy metabolism in the heart, pamidronate worsened systolic function in rats treated with doxorubicin, and therefore we cannot recommend its use in conjunction with anthracycline chemotherapy.Faculdade de Medicina de Botucatu Universidade Estadual Paulista - UNESP, Avenida Dr. Montenegro, s/n. CEP: 18.618-687Faculdade de Medicina de Botucatu Universidade Estadual Paulista - UNESP, Avenida Dr. Montenegro, s/n. CEP: 18.618-687Universidade Estadual Paulista (Unesp)Carvalho, Paula Bernardo De [UNESP]Gonçalves, Andréa De Freitas [UNESP]Alegre, Patrícia Helena Correa [UNESP]Azevedo, Paula Schmidt [UNESP]Roscani, Meliza Goi [UNESP]Bergamasco, Carolina Marabesi [UNESP]Modesto, Pamela N. [UNESP]Fernandes, Ana Angélica [UNESP]Minicucci, Marcos Ferreira [UNESP]Paiva, Sergio Alberto Rupp [UNESP]Antonio, Leonardo [UNESP]Zornoff, Mamede [UNESP]Polegato, Bertha Furlan [UNESP]2018-12-11T17:30:24Z2018-12-11T17:30:24Z2016-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article431-442application/pdfhttp://dx.doi.org/10.1159/000452558Cellular Physiology and Biochemistry, v. 40, n. 3-4, p. 431-442, 2016.1421-97781015-8987http://hdl.handle.net/11449/17845010.1159/0004525582-s2.0-850009784122-s2.0-85000978412.pdf121314080140264774387040344716730000-0002-5843-6232Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengCellular Physiology and Biochemistry1,5611,561info:eu-repo/semantics/openAccess2024-08-14T17:23:10Zoai:repositorio.unesp.br:11449/178450Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-14T17:23:10Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats |
title |
Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats |
spellingShingle |
Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats Carvalho, Paula Bernardo De [UNESP] Hypocalcaemia Isolated heart study Left ventricular dysfunction Matrix metalloproteinase |
title_short |
Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats |
title_full |
Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats |
title_fullStr |
Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats |
title_full_unstemmed |
Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats |
title_sort |
Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats |
author |
Carvalho, Paula Bernardo De [UNESP] |
author_facet |
Carvalho, Paula Bernardo De [UNESP] Gonçalves, Andréa De Freitas [UNESP] Alegre, Patrícia Helena Correa [UNESP] Azevedo, Paula Schmidt [UNESP] Roscani, Meliza Goi [UNESP] Bergamasco, Carolina Marabesi [UNESP] Modesto, Pamela N. [UNESP] Fernandes, Ana Angélica [UNESP] Minicucci, Marcos Ferreira [UNESP] Paiva, Sergio Alberto Rupp [UNESP] Antonio, Leonardo [UNESP] Zornoff, Mamede [UNESP] Polegato, Bertha Furlan [UNESP] |
author_role |
author |
author2 |
Gonçalves, Andréa De Freitas [UNESP] Alegre, Patrícia Helena Correa [UNESP] Azevedo, Paula Schmidt [UNESP] Roscani, Meliza Goi [UNESP] Bergamasco, Carolina Marabesi [UNESP] Modesto, Pamela N. [UNESP] Fernandes, Ana Angélica [UNESP] Minicucci, Marcos Ferreira [UNESP] Paiva, Sergio Alberto Rupp [UNESP] Antonio, Leonardo [UNESP] Zornoff, Mamede [UNESP] Polegato, Bertha Furlan [UNESP] |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Carvalho, Paula Bernardo De [UNESP] Gonçalves, Andréa De Freitas [UNESP] Alegre, Patrícia Helena Correa [UNESP] Azevedo, Paula Schmidt [UNESP] Roscani, Meliza Goi [UNESP] Bergamasco, Carolina Marabesi [UNESP] Modesto, Pamela N. [UNESP] Fernandes, Ana Angélica [UNESP] Minicucci, Marcos Ferreira [UNESP] Paiva, Sergio Alberto Rupp [UNESP] Antonio, Leonardo [UNESP] Zornoff, Mamede [UNESP] Polegato, Bertha Furlan [UNESP] |
dc.subject.por.fl_str_mv |
Hypocalcaemia Isolated heart study Left ventricular dysfunction Matrix metalloproteinase |
topic |
Hypocalcaemia Isolated heart study Left ventricular dysfunction Matrix metalloproteinase |
description |
Background: Cardiotoxicity is the major side effect of doxorubicin. As mechanisms that are involved in cardiotoxicity are ambiguous, new methods for attenuating cardiotoxicity are needed. Recent studies have shown that bisphosphonates can decrease oxidative stress. Therefore, the objective of this study was to evaluate the effect of pamidronate on preventing acute doxorubicin-induced cardiotoxicity. Methods: Sixty-four male Wistar rats were allocated into four groups: the control group (C), the pamidronate group (P), the doxorubicin group (D) and the doxorubicin/pamidronate group (DP). The rats in the P and DP groups received pamidronate injections (3 mg/kg, IP). After 24 hours, the rats in the D and DP groups received doxorubicin injections (20 mg/kg, IP). Forty-eight hours after doxorubicin injection, the rats were killed. Echocardiography, isolated heart study and biochemical analysis were performed. Results: Doxorubicin-induced acute cardiotoxicity showed increased matrix metalloproteinases (MMP)-2 activation, oxidative damage and induced alterations in myocardial energetic metabolism. Pamidronate did not inhibit MMP-2 activation but attenuated oxidative stress and improved myocardial energetic metabolism. Regarding cardiac function, the DP group exhibited a decrease in the left ventricular ejection fraction in the echocardiography and a decrease in +dP/dt in the isolated heart study compared with other groups. The same DP group presented serum hypocalcaemia. Conclusions: Despite its ability to reduce oxidative stress and improve energy metabolism in the heart, pamidronate worsened systolic function in rats treated with doxorubicin, and therefore we cannot recommend its use in conjunction with anthracycline chemotherapy. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-12-01 2018-12-11T17:30:24Z 2018-12-11T17:30:24Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1159/000452558 Cellular Physiology and Biochemistry, v. 40, n. 3-4, p. 431-442, 2016. 1421-9778 1015-8987 http://hdl.handle.net/11449/178450 10.1159/000452558 2-s2.0-85000978412 2-s2.0-85000978412.pdf 1213140801402647 7438704034471673 0000-0002-5843-6232 |
url |
http://dx.doi.org/10.1159/000452558 http://hdl.handle.net/11449/178450 |
identifier_str_mv |
Cellular Physiology and Biochemistry, v. 40, n. 3-4, p. 431-442, 2016. 1421-9778 1015-8987 10.1159/000452558 2-s2.0-85000978412 2-s2.0-85000978412.pdf 1213140801402647 7438704034471673 0000-0002-5843-6232 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Cellular Physiology and Biochemistry 1,561 1,561 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
431-442 application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128154511867904 |