Atividade protetora da diosmina sobre a cardiotoxicidade induzida pela doxorrubicina em camundongos com sarcoma 180
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFS |
Texto Completo: | http://ri.ufs.br/jspui/handle/riufs/15924 |
Resumo: | Protective activity of Diosmin on doxorubicin-induced cardiotoxicity in mice with Sarcoma 180. Sara Albuquerque dos Santos, São Cristovão, 2022. Introduction: Cancer is a serious pathology in the context of public health with high mortality rates. Doxorubicin (Dox) is an antineoplastic used in the treatment of the disease and generates dose-dependent cardiotoxicity caused by oxidative stress, inflammation and apoptosis. Diosmin (Dios), a natural product with an antioxidant, anti-inflammatory and anti-apoptotic effect, shows promise for protecting the cardiac toxic effects caused by Dox. Objective: In this study, the protective activity of Diosmin on doxorubicin-induced cardiotoxicity in mice with Sarcoma 180 (S180) was investigated. Methods: Diosmin interference on cell proliferation was evaluated through in vitro cytotoxicity in 6 cell lines: human breast carcinoma (MCF-7), human colon carcinoma (HCT116), human hepatocellular carcinoma (HepG2), human promyelocytic leukemia (HL-60), human lung fibroblast (MRC-5) and Sarcoma 180 (S180). To evaluate the antitumor activity in vivo, 70 mice were divided into 7 groups: Saline (0.9% p.o.), Positive Control (Cyclophosphamide, 15 mg/kg/day p.o.), Dox alone (2 mg/kg/day i.p.), Dios 50 (50 mg /kg/day p.o.), Dios 100 (100 mg/kg/day p.o.), Dox + Dios 50 (2 mg/kg/day i.p. + 50 mg/kg/day p.o) and Dox + Dios 100 (2 mg/kg/day i.p. + 100 mg/kg/day p.o.), with a 7-day treatment. To assess cardiotoxicity, 50 mice were divided into 5 groups: Saline (0.9% p.o.), Dox (2 mg/kg/day i.p.), S180 + Dox (Dox 2 mg/kg/day i.p.), S180 + Dox + Dios 50 (2 mg/kg/day i.p. + 50 mg/kg/day p.o.) and S180 + Dox + Dios 100 (2 mg/kg/day i.p. + 100 mg/kg/day p.o.) with 9 days treatment. After 24 hours, electrocardiographic evaluation, blood collection and organ removal were performed. Toxicological aspects were evaluated and the antioxidant effect of Diosmin was measured. Finally, the histomorphological analysis of the hearts and tumors was performed. Results: Diosmin showed no inhibition of cell proliferation for any of the 6 cell lines, on the other hand, Dox showed cytotoxic activity for all cell lines. Regarding in vivo antitumor activity, the Dios groups at doses of 50 and 100 mg/kg/day associated with Dox (2 mg/kg/day) when compared to the saline group showed a significant reduction in tumor growth (inhibition of 48.8 % and 43.4%, respectively). However, when compared to the Dox (2 mg/kg/day) group alone, there was no statistically significant difference (p > 0.05). These results showed that Diosmin at the doses tested did not interfere with the antitumor activity of Dox against the S180 model. The evaluation of the electrocardiographic recordings showed that the groups treated with Dox (with and without S180) showed significant variations (p<0.05) in the ECG in relation to the PRi and QTc intervals and the Heart Rate (HR) when compared to the saline group. Diosmin, however, recovered the PRi, QTc and HR intervals. In addition, regarding toxicological aspects, Diosmin preserved cardiac mass, reduced cardiac injury markers (AST, CK-MB, LDH) and at a dose of 100 mg/kg/day, recovered the leukocyte pattern. When evaluating the antioxidant effect, Diosmin protected the heart against lipid peroxidation and restored the activity of endogenous antioxidant enzymes. Histologically, Diosmin promoted a noticeable reduction in the areas of morphological alterations such as hydropic vacuolar degeneration, expressed by “ballooned” morphology, induced by Dox. Conclusion: This study demonstrated that Diosmin recovered electrocardiographic patterns, minimized toxicological effects, reestablished antioxidant activity and preserved cardiac morphohistological architecture, without interfering with the antitumor activity of Dox. |
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Santos, Sara Albuquerque dosSantos, Sandra LautonAmaral, Ricardo Guimarães2022-06-23T16:11:26Z2022-06-23T16:11:26Z2022-05-31SANTOS, Sara Albuquerque dos. Atividade protetora da diosmina sobre a cardiotoxicidade induzida pela doxorrubicina em camundongos com sarcoma 180. 2022. 112 f. Tese (Doutorado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, SE, 2022.http://ri.ufs.br/jspui/handle/riufs/15924Protective activity of Diosmin on doxorubicin-induced cardiotoxicity in mice with Sarcoma 180. Sara Albuquerque dos Santos, São Cristovão, 2022. Introduction: Cancer is a serious pathology in the context of public health with high mortality rates. Doxorubicin (Dox) is an antineoplastic used in the treatment of the disease and generates dose-dependent cardiotoxicity caused by oxidative stress, inflammation and apoptosis. Diosmin (Dios), a natural product with an antioxidant, anti-inflammatory and anti-apoptotic effect, shows promise for protecting the cardiac toxic effects caused by Dox. Objective: In this study, the protective activity of Diosmin on doxorubicin-induced cardiotoxicity in mice with Sarcoma 180 (S180) was investigated. Methods: Diosmin interference on cell proliferation was evaluated through in vitro cytotoxicity in 6 cell lines: human breast carcinoma (MCF-7), human colon carcinoma (HCT116), human hepatocellular carcinoma (HepG2), human promyelocytic leukemia (HL-60), human lung fibroblast (MRC-5) and Sarcoma 180 (S180). To evaluate the antitumor activity in vivo, 70 mice were divided into 7 groups: Saline (0.9% p.o.), Positive Control (Cyclophosphamide, 15 mg/kg/day p.o.), Dox alone (2 mg/kg/day i.p.), Dios 50 (50 mg /kg/day p.o.), Dios 100 (100 mg/kg/day p.o.), Dox + Dios 50 (2 mg/kg/day i.p. + 50 mg/kg/day p.o) and Dox + Dios 100 (2 mg/kg/day i.p. + 100 mg/kg/day p.o.), with a 7-day treatment. To assess cardiotoxicity, 50 mice were divided into 5 groups: Saline (0.9% p.o.), Dox (2 mg/kg/day i.p.), S180 + Dox (Dox 2 mg/kg/day i.p.), S180 + Dox + Dios 50 (2 mg/kg/day i.p. + 50 mg/kg/day p.o.) and S180 + Dox + Dios 100 (2 mg/kg/day i.p. + 100 mg/kg/day p.o.) with 9 days treatment. After 24 hours, electrocardiographic evaluation, blood collection and organ removal were performed. Toxicological aspects were evaluated and the antioxidant effect of Diosmin was measured. Finally, the histomorphological analysis of the hearts and tumors was performed. Results: Diosmin showed no inhibition of cell proliferation for any of the 6 cell lines, on the other hand, Dox showed cytotoxic activity for all cell lines. Regarding in vivo antitumor activity, the Dios groups at doses of 50 and 100 mg/kg/day associated with Dox (2 mg/kg/day) when compared to the saline group showed a significant reduction in tumor growth (inhibition of 48.8 % and 43.4%, respectively). However, when compared to the Dox (2 mg/kg/day) group alone, there was no statistically significant difference (p > 0.05). These results showed that Diosmin at the doses tested did not interfere with the antitumor activity of Dox against the S180 model. The evaluation of the electrocardiographic recordings showed that the groups treated with Dox (with and without S180) showed significant variations (p<0.05) in the ECG in relation to the PRi and QTc intervals and the Heart Rate (HR) when compared to the saline group. Diosmin, however, recovered the PRi, QTc and HR intervals. In addition, regarding toxicological aspects, Diosmin preserved cardiac mass, reduced cardiac injury markers (AST, CK-MB, LDH) and at a dose of 100 mg/kg/day, recovered the leukocyte pattern. When evaluating the antioxidant effect, Diosmin protected the heart against lipid peroxidation and restored the activity of endogenous antioxidant enzymes. Histologically, Diosmin promoted a noticeable reduction in the areas of morphological alterations such as hydropic vacuolar degeneration, expressed by “ballooned” morphology, induced by Dox. Conclusion: This study demonstrated that Diosmin recovered electrocardiographic patterns, minimized toxicological effects, reestablished antioxidant activity and preserved cardiac morphohistological architecture, without interfering with the antitumor activity of Dox.Atividade protetora da Diosmina sobre a cardiotoxicidade induzida pela doxorrubicina em camundongos com Sarcoma 180. Sara Albuquerque dos Santos, São Cristovão, 2022. Introdução: O câncer é uma patologia grave no contexto de saúde pública com altas taxas de mortalidade. A doxorrubicina (Dox) é um antineoplásico utilizado no tratamento da doença e gera cardiotoxicidade dose-dependente ocasionada por estresse oxidativo, inflamação e apoptose. A Diosmina (Dios), um produto natural com efeito antioxidante, anti-inflamatório e antiapoptótico, mostra-se promissora para proteção dos efeitos tóxicos cardíacos ocasionados pela Doxorrubicina. Objetivo: Neste estudo foi investigada a atividade protetora da Diosmina sobre a cardiotoxicidade induzida pela Doxorrubicina em camundongos com Sarcoma 180 (S180). Métodos: Foi avaliada a interferência da Diosmina na proliferação celular através da citotoxicidade in vitro em 6 linhagens de células: carcinoma de mama humano (MCF-7), carcinoma de colón humano (HCT116), carcinoma hepatocelular humano (HepG2), leucemia promielocítica humana (HL-60), fibroblasto de pulmão humano (MRC-5) e Sarcoma 180 (S180). Para avaliação da atividade antitumoral in vivo utilizou-se 70 camundongos divididos 7 grupos: Salina (0,9% v.o.), Controle positivo (Ciclofosfamida, 15 mg/kg/dia v.o.), Dox isolado (2 mg/kg/dia i.p.), Dios 50 (50 mg/kg/dia v.o.), Dios 100 (100 mg/kg/dia v.o.), Dox + Dios 50 (2 mg/kg/dia i.p. + 50 mg/kg/dia v.o.) e Dox + Dios 100 (2 mg/kg/dia i.p. + 100 mg/kg/dia v.o.), com tratamento de 7 dias. Para avaliação da cardiotoxicidade utilizou-se 50 camundongos divididos em 5 grupos: Salina (0,9% v.o.), Dox (2 mg/kg/dia i.p.), S180 + Dox (Dox 2 mg/kg/dia i.p.), S180 + Dox + Dios 50 (2 mg/kg/dia i.p. + 50 mg/kg/dia v.o.) e S180 + Dox + Dios 100 (2 mg/kg/dia i.p. + 100 mg/kg/dia v.o.) com tratamento de 9 dias. Após 24hs foi realizada a avaliação eletrocardiográfica, coleta de sangue e retirada de órgãos. Foram avaliados aspectos toxicológicos e mensurou-se o efeito antioxidante da Diosmina. Por fim, foi feita a análise histomorfológica dos corações e dos tumores. Resultados: A Diosmina não apresentou inibição de proliferação celular para nenhuma das 6 linhagens de células, em contrapartida, a Doxorrubicina apresentou atividade citotóxica para todas as linhagens celulares. Em relação à atividade antitumoral in vivo, os grupos Dios nas doses de 50 e 100 mg/kg/dia associados a Dox (2 mg/kg/dia) quando comparados ao grupo salina, apresentaram redução significativa do crescimento tumoral (inibição de 48,8 % e 43,4 %, respectivamente). No entanto, quando comparados ao grupo Dox (2 mg/kg/dia) isolado, não houve diferença estatística significativa (p > 0,05). Esses resultados mostraram que a Diosmina nas doses testadas não interferiu na atividade antitumoral da Dox frente ao modelo S180. A avaliação dos registros eletrocardiográficos mostrou que os grupos tratados com Dox (sem e com S180) demonstraram variações significativas (p<0,05) no ECG em relação aos intervalos PRi e QTc e à Frequência Cardíaca (FC) quando comparados ao grupo salina. A Diosmina, no entanto, recuperou os intervalos PRi, QTc e a FC. Além disso, em relação aos aspectos toxicológicos, a Diosmina preservou a massa cardíaca, reduziu os marcadores de lesão cardíaca (AST, CKMB, LDH) e na dose de 100 mg/kg/dia, recuperou o padrão leucocitário. Quando avaliado o efeito antioxidante, a Diosmina protegeu o coração contra peroxidação lipídica e restaurou a atividade das enzimas antioxidantes endógenas. Histologicamente, a Diosmina promoveu notada redução das áreas de alterações morfológicas como degeneração vacuolar hidrópica, expressa por morfologia “balonizada”, induzidas pela Dox. Conclusão: Este estudo demonstrou que a Diosmina recuperou os padrões eletrocardiográficos, minimizou os efeitos toxicológicos, reestabeleceu a atividade antioxidante e preservou a arquitetura morfohistológica cardíaca, sem interferir na atividade antitumoral da Dox.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESSão Cristóvão, SEporFisiologiaCâncerFlavonoidesCardiotoxicidadeDoxorrubicinaDiosminaCancerDoxorubicinCardiotoxicityFlavonoidsDiosminCIENCIAS BIOLOGICAS::FISIOLOGIAAtividade protetora da diosmina sobre a cardiotoxicidade induzida pela doxorrubicina em camundongos com sarcoma 180info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisPós-Graduação em Ciências FisiológicasUniversidade Federal de Sergipereponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81475https://ri.ufs.br/jspui/bitstream/riufs/15924/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51ORIGINALSARA_ALBUQUERQUE_SANTOS.pdfSARA_ALBUQUERQUE_SANTOS.pdfapplication/pdf2930937https://ri.ufs.br/jspui/bitstream/riufs/15924/2/SARA_ALBUQUERQUE_SANTOS.pdfbe2c2c0afd71569aa72982000da12dd3MD52TEXTSARA_ALBUQUERQUE_SANTOS.pdf.txtSARA_ALBUQUERQUE_SANTOS.pdf.txtExtracted texttext/plain232431https://ri.ufs.br/jspui/bitstream/riufs/15924/3/SARA_ALBUQUERQUE_SANTOS.pdf.txt0a6479f79fa0815caea0b1b2297be86eMD53THUMBNAILSARA_ALBUQUERQUE_SANTOS.pdf.jpgSARA_ALBUQUERQUE_SANTOS.pdf.jpgGenerated Thumbnailimage/jpeg1387https://ri.ufs.br/jspui/bitstream/riufs/15924/4/SARA_ALBUQUERQUE_SANTOS.pdf.jpg746a79c54081d6cf536bb67e83c2ffa5MD54riufs/159242022-06-23 13:11:38.508oai:ufs.br:riufs/15924TElDRU7Dh0EgREUgRElTVFJJQlVJw4fDg08gTsODTy1FWENMVVNJVkEKCkNvbSBhIGFwcmVzZW50YcOnw6NvIGRlc3RhIGxpY2Vuw6dhLCB2b2PDqiAobyBhdXRvcihlcykgb3UgbyB0aXR1bGFyIGRvcyBkaXJlaXRvcyBkZSBhdXRvcikgY29uY2VkZSDDoCBVbml2ZXJzaWRhZGUgRmVkZXJhbCBkZSBTZXJnaXBlIG8gZGlyZWl0byBuw6NvLWV4Y2x1c2l2byBkZSByZXByb2R1emlyIHNldSB0cmFiYWxobyBubyBmb3JtYXRvIGVsZXRyw7RuaWNvLCBpbmNsdWluZG8gb3MgZm9ybWF0b3Mgw6F1ZGlvIG91IHbDrWRlby4KClZvY8OqIGNvbmNvcmRhIHF1ZSBhIFVuaXZlcnNpZGFkZSBGZWRlcmFsIGRlIFNlcmdpcGUgcG9kZSwgc2VtIGFsdGVyYXIgbyBjb250ZcO6ZG8sIHRyYW5zcG9yIHNldSB0cmFiYWxobyBwYXJhIHF1YWxxdWVyIG1laW8gb3UgZm9ybWF0byBwYXJhIGZpbnMgZGUgcHJlc2VydmHDp8Ojby4KClZvY8OqIHRhbWLDqW0gY29uY29yZGEgcXVlIGEgVW5pdmVyc2lkYWRlIEZlZGVyYWwgZGUgU2VyZ2lwZSBwb2RlIG1hbnRlciBtYWlzIGRlIHVtYSBjw7NwaWEgZGUgc2V1IHRyYWJhbGhvIHBhcmEgZmlucyBkZSBzZWd1cmFuw6dhLCBiYWNrLXVwIGUgcHJlc2VydmHDp8Ojby4KClZvY8OqIGRlY2xhcmEgcXVlIHNldSB0cmFiYWxobyDDqSBvcmlnaW5hbCBlIHF1ZSB2b2PDqiB0ZW0gbyBwb2RlciBkZSBjb25jZWRlciBvcyBkaXJlaXRvcyBjb250aWRvcyBuZXN0YSBsaWNlbsOnYS4gVm9jw6ogdGFtYsOpbSBkZWNsYXJhIHF1ZSBvIGRlcMOzc2l0bywgcXVlIHNlamEgZGUgc2V1IGNvbmhlY2ltZW50bywgbsOjbyBpbmZyaW5nZSBkaXJlaXRvcyBhdXRvcmFpcyBkZSBuaW5ndcOpbS4KCkNhc28gbyB0cmFiYWxobyBjb250ZW5oYSBtYXRlcmlhbCBxdWUgdm9jw6ogbsOjbyBwb3NzdWkgYSB0aXR1bGFyaWRhZGUgZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCB2b2PDqiBkZWNsYXJhIHF1ZSBvYnRldmUgYSBwZXJtaXNzw6NvIGlycmVzdHJpdGEgZG8gZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIHBhcmEgY29uY2VkZXIgw6AgVW5pdmVyc2lkYWRlIEZlZGVyYWwgZGUgU2VyZ2lwZSBvcyBkaXJlaXRvcyBhcHJlc2VudGFkb3MgbmVzdGEgbGljZW7Dp2EsIGUgcXVlIGVzc2UgbWF0ZXJpYWwgZGUgcHJvcHJpZWRhZGUgZGUgdGVyY2Vpcm9zIGVzdMOhIGNsYXJhbWVudGUgaWRlbnRpZmljYWRvIGUgcmVjb25oZWNpZG8gbm8gdGV4dG8gb3Ugbm8gY29udGXDumRvLgoKQSBVbml2ZXJzaWRhZGUgRmVkZXJhbCBkZSBTZXJnaXBlIHNlIGNvbXByb21ldGUgYSBpZGVudGlmaWNhciBjbGFyYW1lbnRlIG8gc2V1IG5vbWUocykgb3UgbyhzKSBub21lKHMpIGRvKHMpIApkZXRlbnRvcihlcykgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIGRvIHRyYWJhbGhvLCBlIG7Do28gZmFyw6EgcXVhbHF1ZXIgYWx0ZXJhw6fDo28sIGFsw6ltIGRhcXVlbGFzIGNvbmNlZGlkYXMgcG9yIGVzdGEgbGljZW7Dp2EuIAo=Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2022-06-23T16:11:38Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false |
dc.title.pt_BR.fl_str_mv |
Atividade protetora da diosmina sobre a cardiotoxicidade induzida pela doxorrubicina em camundongos com sarcoma 180 |
title |
Atividade protetora da diosmina sobre a cardiotoxicidade induzida pela doxorrubicina em camundongos com sarcoma 180 |
spellingShingle |
Atividade protetora da diosmina sobre a cardiotoxicidade induzida pela doxorrubicina em camundongos com sarcoma 180 Santos, Sara Albuquerque dos Fisiologia Câncer Flavonoides Cardiotoxicidade Doxorrubicina Diosmina Cancer Doxorubicin Cardiotoxicity Flavonoids Diosmin CIENCIAS BIOLOGICAS::FISIOLOGIA |
title_short |
Atividade protetora da diosmina sobre a cardiotoxicidade induzida pela doxorrubicina em camundongos com sarcoma 180 |
title_full |
Atividade protetora da diosmina sobre a cardiotoxicidade induzida pela doxorrubicina em camundongos com sarcoma 180 |
title_fullStr |
Atividade protetora da diosmina sobre a cardiotoxicidade induzida pela doxorrubicina em camundongos com sarcoma 180 |
title_full_unstemmed |
Atividade protetora da diosmina sobre a cardiotoxicidade induzida pela doxorrubicina em camundongos com sarcoma 180 |
title_sort |
Atividade protetora da diosmina sobre a cardiotoxicidade induzida pela doxorrubicina em camundongos com sarcoma 180 |
author |
Santos, Sara Albuquerque dos |
author_facet |
Santos, Sara Albuquerque dos |
author_role |
author |
dc.contributor.author.fl_str_mv |
Santos, Sara Albuquerque dos |
dc.contributor.advisor1.fl_str_mv |
Santos, Sandra Lauton |
dc.contributor.advisor-co1.fl_str_mv |
Amaral, Ricardo Guimarães |
contributor_str_mv |
Santos, Sandra Lauton Amaral, Ricardo Guimarães |
dc.subject.por.fl_str_mv |
Fisiologia Câncer Flavonoides Cardiotoxicidade Doxorrubicina Diosmina |
topic |
Fisiologia Câncer Flavonoides Cardiotoxicidade Doxorrubicina Diosmina Cancer Doxorubicin Cardiotoxicity Flavonoids Diosmin CIENCIAS BIOLOGICAS::FISIOLOGIA |
dc.subject.eng.fl_str_mv |
Cancer Doxorubicin Cardiotoxicity Flavonoids Diosmin |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::FISIOLOGIA |
description |
Protective activity of Diosmin on doxorubicin-induced cardiotoxicity in mice with Sarcoma 180. Sara Albuquerque dos Santos, São Cristovão, 2022. Introduction: Cancer is a serious pathology in the context of public health with high mortality rates. Doxorubicin (Dox) is an antineoplastic used in the treatment of the disease and generates dose-dependent cardiotoxicity caused by oxidative stress, inflammation and apoptosis. Diosmin (Dios), a natural product with an antioxidant, anti-inflammatory and anti-apoptotic effect, shows promise for protecting the cardiac toxic effects caused by Dox. Objective: In this study, the protective activity of Diosmin on doxorubicin-induced cardiotoxicity in mice with Sarcoma 180 (S180) was investigated. Methods: Diosmin interference on cell proliferation was evaluated through in vitro cytotoxicity in 6 cell lines: human breast carcinoma (MCF-7), human colon carcinoma (HCT116), human hepatocellular carcinoma (HepG2), human promyelocytic leukemia (HL-60), human lung fibroblast (MRC-5) and Sarcoma 180 (S180). To evaluate the antitumor activity in vivo, 70 mice were divided into 7 groups: Saline (0.9% p.o.), Positive Control (Cyclophosphamide, 15 mg/kg/day p.o.), Dox alone (2 mg/kg/day i.p.), Dios 50 (50 mg /kg/day p.o.), Dios 100 (100 mg/kg/day p.o.), Dox + Dios 50 (2 mg/kg/day i.p. + 50 mg/kg/day p.o) and Dox + Dios 100 (2 mg/kg/day i.p. + 100 mg/kg/day p.o.), with a 7-day treatment. To assess cardiotoxicity, 50 mice were divided into 5 groups: Saline (0.9% p.o.), Dox (2 mg/kg/day i.p.), S180 + Dox (Dox 2 mg/kg/day i.p.), S180 + Dox + Dios 50 (2 mg/kg/day i.p. + 50 mg/kg/day p.o.) and S180 + Dox + Dios 100 (2 mg/kg/day i.p. + 100 mg/kg/day p.o.) with 9 days treatment. After 24 hours, electrocardiographic evaluation, blood collection and organ removal were performed. Toxicological aspects were evaluated and the antioxidant effect of Diosmin was measured. Finally, the histomorphological analysis of the hearts and tumors was performed. Results: Diosmin showed no inhibition of cell proliferation for any of the 6 cell lines, on the other hand, Dox showed cytotoxic activity for all cell lines. Regarding in vivo antitumor activity, the Dios groups at doses of 50 and 100 mg/kg/day associated with Dox (2 mg/kg/day) when compared to the saline group showed a significant reduction in tumor growth (inhibition of 48.8 % and 43.4%, respectively). However, when compared to the Dox (2 mg/kg/day) group alone, there was no statistically significant difference (p > 0.05). These results showed that Diosmin at the doses tested did not interfere with the antitumor activity of Dox against the S180 model. The evaluation of the electrocardiographic recordings showed that the groups treated with Dox (with and without S180) showed significant variations (p<0.05) in the ECG in relation to the PRi and QTc intervals and the Heart Rate (HR) when compared to the saline group. Diosmin, however, recovered the PRi, QTc and HR intervals. In addition, regarding toxicological aspects, Diosmin preserved cardiac mass, reduced cardiac injury markers (AST, CK-MB, LDH) and at a dose of 100 mg/kg/day, recovered the leukocyte pattern. When evaluating the antioxidant effect, Diosmin protected the heart against lipid peroxidation and restored the activity of endogenous antioxidant enzymes. Histologically, Diosmin promoted a noticeable reduction in the areas of morphological alterations such as hydropic vacuolar degeneration, expressed by “ballooned” morphology, induced by Dox. Conclusion: This study demonstrated that Diosmin recovered electrocardiographic patterns, minimized toxicological effects, reestablished antioxidant activity and preserved cardiac morphohistological architecture, without interfering with the antitumor activity of Dox. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-06-23T16:11:26Z |
dc.date.available.fl_str_mv |
2022-06-23T16:11:26Z |
dc.date.issued.fl_str_mv |
2022-05-31 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
SANTOS, Sara Albuquerque dos. Atividade protetora da diosmina sobre a cardiotoxicidade induzida pela doxorrubicina em camundongos com sarcoma 180. 2022. 112 f. Tese (Doutorado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, SE, 2022. |
dc.identifier.uri.fl_str_mv |
http://ri.ufs.br/jspui/handle/riufs/15924 |
identifier_str_mv |
SANTOS, Sara Albuquerque dos. Atividade protetora da diosmina sobre a cardiotoxicidade induzida pela doxorrubicina em camundongos com sarcoma 180. 2022. 112 f. Tese (Doutorado em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, SE, 2022. |
url |
http://ri.ufs.br/jspui/handle/riufs/15924 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.program.fl_str_mv |
Pós-Graduação em Ciências Fisiológicas |
dc.publisher.initials.fl_str_mv |
Universidade Federal de Sergipe |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFS instname:Universidade Federal de Sergipe (UFS) instacron:UFS |
instname_str |
Universidade Federal de Sergipe (UFS) |
instacron_str |
UFS |
institution |
UFS |
reponame_str |
Repositório Institucional da UFS |
collection |
Repositório Institucional da UFS |
bitstream.url.fl_str_mv |
https://ri.ufs.br/jspui/bitstream/riufs/15924/1/license.txt https://ri.ufs.br/jspui/bitstream/riufs/15924/2/SARA_ALBUQUERQUE_SANTOS.pdf https://ri.ufs.br/jspui/bitstream/riufs/15924/3/SARA_ALBUQUERQUE_SANTOS.pdf.txt https://ri.ufs.br/jspui/bitstream/riufs/15924/4/SARA_ALBUQUERQUE_SANTOS.pdf.jpg |
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bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS) |
repository.mail.fl_str_mv |
repositorio@academico.ufs.br |
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1802110678884941824 |