Efeito cardioprotetor do d-limoneno sobre o infarto agudo do miocárdio em modelo animal

Detalhes bibliográficos
Autor(a) principal: Durço, Aimée Obolari
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFS
Texto Completo: https://ri.ufs.br/jspui/handle/riufs/13884
Resumo: Acute myocardial infarction (MI) presents a high mortality rate and its approach - pharmacological or percutaneous - does not significantly inhibit the ischemia / reperfusion (RI) damage caused, among others, by the increase of oxidative stress. The therapeutic properties of monoterpenes are already known and studies have shown that d-limonene - the most common natural monoterpene in nature, has antioxidant capacity and hypotensive action on blood pressure. Thus, the project sought to evaluate the cardioprotective effect of d-limonene on the IM model in the heart of Swiss mice. The animals were divided into 4 groups: control (vehicle - saline 0.9% + DMSO 0.1%), myocardial infarction (vehicle + 150mg / kg isoproterenol), d - limonene - DL 10μM d-limonene) and IM + DL (vehicle + isoproterenol + d-limonene) - the drugs were administered intraperitoneally, in two separate doses over a 24 hours interval. In the IM + DL group, d-limonene was administered 30 minutes after isoproterenol administration. Thus, subdermal electrodes were used to characterize the effect of d-limonene on electrocardiographic alterations; investigation of the effects of d-limonene on the infarct area by TTC labeling; histological changes by hematoxylin/eosin staining method (H & E); production of EROs by fluorescence with DHE; evaluation of the response of d-limonene to the antioxidant enzymes SOD and CAT its antioxidant capacity (FRAP) and action on the anti and pro-apoptotic proteins by immunofluorescence and Western Blotting techniques. Values of probability of p <0.05 were considered statistically significant. All data were expressed as mean ± Standard Mean Error (SEM), and the number of animals 5-6 per group. The results showed that d-limonene prevented ST segment elevation in 30% of the evaluated animals, prevented the increase of the QTc (71,66 ± 6,604 from 102,9 ± 5,04) and FC (332,7 ± 20,96 from 500,6 ± 13,69 bpm) interval, reduced the infarct area to 8.34%, and prevented histological changes in muscle fibers as well as decreased mononuclear cell infiltration, decreased oxidative stress by decreasing the ROS, restoring the SOD activity to values close to the control (24.35 ± 3.87 U/mg), to decrease the sulfidrylation, carbonylation and lipid peroxidation, and suppressed proapoptotic by reducing the expression of Bax and the activation of pro-caspase 3 to parameters equal to the control (93,54 ± 3,15 e 100 ± 2,37, respectively). Thus, the pharmacological findings of d-limonene converge to decrease the pro-apoptotic effect by reducing pro-apoptotic enzymes, reducing the infarct area, and producing ROS and increasing SOD activity.
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spelling Durço, Aimée ObolariBarreto, André Sales2021-01-06T18:55:30Z2021-01-06T18:55:30Z2019-07-24DURÇO, Aimée Obolari. Efeito cardioprotetor do d-limoneno sobre o infarto agudo do miocárdio em modelo animal. 2019. Dissertação (Mestrado em Ciências Aplicadas à Saúde) - Universidade Federal de Sergipe, Lagarto, 2019.https://ri.ufs.br/jspui/handle/riufs/13884Acute myocardial infarction (MI) presents a high mortality rate and its approach - pharmacological or percutaneous - does not significantly inhibit the ischemia / reperfusion (RI) damage caused, among others, by the increase of oxidative stress. The therapeutic properties of monoterpenes are already known and studies have shown that d-limonene - the most common natural monoterpene in nature, has antioxidant capacity and hypotensive action on blood pressure. Thus, the project sought to evaluate the cardioprotective effect of d-limonene on the IM model in the heart of Swiss mice. The animals were divided into 4 groups: control (vehicle - saline 0.9% + DMSO 0.1%), myocardial infarction (vehicle + 150mg / kg isoproterenol), d - limonene - DL 10μM d-limonene) and IM + DL (vehicle + isoproterenol + d-limonene) - the drugs were administered intraperitoneally, in two separate doses over a 24 hours interval. In the IM + DL group, d-limonene was administered 30 minutes after isoproterenol administration. Thus, subdermal electrodes were used to characterize the effect of d-limonene on electrocardiographic alterations; investigation of the effects of d-limonene on the infarct area by TTC labeling; histological changes by hematoxylin/eosin staining method (H & E); production of EROs by fluorescence with DHE; evaluation of the response of d-limonene to the antioxidant enzymes SOD and CAT its antioxidant capacity (FRAP) and action on the anti and pro-apoptotic proteins by immunofluorescence and Western Blotting techniques. Values of probability of p <0.05 were considered statistically significant. All data were expressed as mean ± Standard Mean Error (SEM), and the number of animals 5-6 per group. The results showed that d-limonene prevented ST segment elevation in 30% of the evaluated animals, prevented the increase of the QTc (71,66 ± 6,604 from 102,9 ± 5,04) and FC (332,7 ± 20,96 from 500,6 ± 13,69 bpm) interval, reduced the infarct area to 8.34%, and prevented histological changes in muscle fibers as well as decreased mononuclear cell infiltration, decreased oxidative stress by decreasing the ROS, restoring the SOD activity to values close to the control (24.35 ± 3.87 U/mg), to decrease the sulfidrylation, carbonylation and lipid peroxidation, and suppressed proapoptotic by reducing the expression of Bax and the activation of pro-caspase 3 to parameters equal to the control (93,54 ± 3,15 e 100 ± 2,37, respectively). Thus, the pharmacological findings of d-limonene converge to decrease the pro-apoptotic effect by reducing pro-apoptotic enzymes, reducing the infarct area, and producing ROS and increasing SOD activity.O infarto agudo do miocárdio (IM) apresenta alta taxa de mortalidade e sua abordagem - farmacológica ou percutânea - não inibe significativamente os danos do processo de isquemia/reperfusão (IR) ocasionados, dentre outros, pelo aumento do estresse oxidativo. As propriedades terapêuticas dos monoterpenos já são conhecidas e estudos já comprovaram que o d-limoneno – o monoterpeno natural mais frequente na natureza, possui capacidade antioxidante e ação hipotensora sobre a pressão sanguínea. Assim, o projeto buscou avaliar o efeito cardioprotetor do d-limoneno emmodelo de IM em coração de camundongo Swiss. Para tanto, animais foram divididos em 4 grupos: controle (veículo – salina 0,9%+DMSO 0,1%), infarto do miocárdio - IM (veículo + 150mg/kg isoproterenol), d-limoneno - DL (veículo + 10µMd-limoneno) e IM + DL (veículo + isoproterenol + d-limoneno) - as drogas foram administradas via intraperitoneal, em duas doses separadas por um intervalo de 24hs.No grupo IM + DL foi feita a dministração do d-limoneno 30 minutos após a administração do isoproterenol. Assim, foram utilizados eletrodos subdérmicos para a caracterização do efeito do d-limoneno sobre as alterações eletrocardiográficas; investigação dos efeitos do d-limoneno sobre a área de infarto através da marcação com TTC; alterações histológicas pelo método de coloração com hematoxilina/eosina (H&E); produção das EROs pela fluorescência com DHE; avaliação da resposta do dlimoneno sobre as enzimas antioxidantes SOD e CAT; sua capacidade antioxidante (FRAP) e ação sobre as proteínas anti e pró-apoptóticas pelas técnicas de imunofluorescência e Western Blotting. Valores de probabilidade de p<0,05 foram considerados estatisticamente significativos. Todos os dados foram expressos como média ± Erro Padrão Médio (EPM), e o número de animais 5 - 6 por grupo. Os resultados mostraram que o d-limoneno impediu a elevação do segmento ST em 30% dos animais avaliados, impediu o aumento do intervalo QTc (de 71,66 ± 6,604 para 102,9 ± 5,04) e da FC (332,7 ± 20,96 para 500,6 ± 13,69 bpm), reduziu a área de infarto para 8,34% e preveniu alterações histológicas nas fibras musculares cardíacas como descontinuidade, degeneração, espaçamento amplo e vacuolações, também diminuiu a infiltração de células mononucleares, diminuiu o estresse oxidativo por diminuir as EROs, restaurar a atividade da SOD a valores próximos ao controle (24,35 ± 3,87 U/mg), diminuir a sulfidrilação, carbonilação e peroxidação lipídica, e suprimiu via pró-apoptótica reduzindo a expressão da Bax e a ativação da pro-caspase 3 a parâmetros iguais ao controle (93,54 ± 3,15 e 100 ± 2,37, respectivamente). Assim, os achados farmacológicos do d-limoneno convergem para a diminuição do efeito próapoptótico pela redução de enzimas pró-apoptóticas, redução da área de infarto e produção de EROs e aumento da atividade da SOD.LagartoporInfarto do miocárdioStress oxidativoInfarto agudo do miocárdioEstresse oxidativoD-limonenoAcute myocardial infarctionReperfusion injuryOxidative stressD-limoneneEfeito cardioprotetor do d-limoneno sobre o infarto agudo do miocárdio em modelo animalinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisPós-Graduação em Ciências Aplicadas à SaúdeUFSreponame: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/13884/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51ORIGINALAIMÉE_OBOLARI_DURÇO.pdfAIMÉE_OBOLARI_DURÇO.pdfapplication/pdf1574461https://ri.ufs.br/jspui/bitstream/riufs/13884/2/AIM%c3%89E_OBOLARI_DUR%c3%87O.pdfef86f8f7bfaff8d9909e2f33c76ba2deMD52TEXTAIMÉE_OBOLARI_DURÇO.pdf.txtAIMÉE_OBOLARI_DURÇO.pdf.txtExtracted texttext/plain154798https://ri.ufs.br/jspui/bitstream/riufs/13884/3/AIM%c3%89E_OBOLARI_DUR%c3%87O.pdf.txt7c5d73a3ac4e064ea140b306971e42d3MD53THUMBNAILAIMÉE_OBOLARI_DURÇO.pdf.jpgAIMÉE_OBOLARI_DURÇO.pdf.jpgGenerated Thumbnailimage/jpeg1362https://ri.ufs.br/jspui/bitstream/riufs/13884/4/AIM%c3%89E_OBOLARI_DUR%c3%87O.pdf.jpg62403f26c72391c0192ff03e26a0c1a7MD54riufs/138842021-01-06 15:55:31.02oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2021-01-06T18:55:31Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false
dc.title.pt_BR.fl_str_mv Efeito cardioprotetor do d-limoneno sobre o infarto agudo do miocárdio em modelo animal
title Efeito cardioprotetor do d-limoneno sobre o infarto agudo do miocárdio em modelo animal
spellingShingle Efeito cardioprotetor do d-limoneno sobre o infarto agudo do miocárdio em modelo animal
Durço, Aimée Obolari
Infarto do miocárdio
Stress oxidativo
Infarto agudo do miocárdio
Estresse oxidativo
D-limoneno
Acute myocardial infarction
Reperfusion injury
Oxidative stress
D-limonene
title_short Efeito cardioprotetor do d-limoneno sobre o infarto agudo do miocárdio em modelo animal
title_full Efeito cardioprotetor do d-limoneno sobre o infarto agudo do miocárdio em modelo animal
title_fullStr Efeito cardioprotetor do d-limoneno sobre o infarto agudo do miocárdio em modelo animal
title_full_unstemmed Efeito cardioprotetor do d-limoneno sobre o infarto agudo do miocárdio em modelo animal
title_sort Efeito cardioprotetor do d-limoneno sobre o infarto agudo do miocárdio em modelo animal
author Durço, Aimée Obolari
author_facet Durço, Aimée Obolari
author_role author
dc.contributor.author.fl_str_mv Durço, Aimée Obolari
dc.contributor.advisor1.fl_str_mv Barreto, André Sales
contributor_str_mv Barreto, André Sales
dc.subject.por.fl_str_mv Infarto do miocárdio
Stress oxidativo
Infarto agudo do miocárdio
Estresse oxidativo
D-limoneno
topic Infarto do miocárdio
Stress oxidativo
Infarto agudo do miocárdio
Estresse oxidativo
D-limoneno
Acute myocardial infarction
Reperfusion injury
Oxidative stress
D-limonene
dc.subject.eng.fl_str_mv Acute myocardial infarction
Reperfusion injury
Oxidative stress
D-limonene
description Acute myocardial infarction (MI) presents a high mortality rate and its approach - pharmacological or percutaneous - does not significantly inhibit the ischemia / reperfusion (RI) damage caused, among others, by the increase of oxidative stress. The therapeutic properties of monoterpenes are already known and studies have shown that d-limonene - the most common natural monoterpene in nature, has antioxidant capacity and hypotensive action on blood pressure. Thus, the project sought to evaluate the cardioprotective effect of d-limonene on the IM model in the heart of Swiss mice. The animals were divided into 4 groups: control (vehicle - saline 0.9% + DMSO 0.1%), myocardial infarction (vehicle + 150mg / kg isoproterenol), d - limonene - DL 10μM d-limonene) and IM + DL (vehicle + isoproterenol + d-limonene) - the drugs were administered intraperitoneally, in two separate doses over a 24 hours interval. In the IM + DL group, d-limonene was administered 30 minutes after isoproterenol administration. Thus, subdermal electrodes were used to characterize the effect of d-limonene on electrocardiographic alterations; investigation of the effects of d-limonene on the infarct area by TTC labeling; histological changes by hematoxylin/eosin staining method (H & E); production of EROs by fluorescence with DHE; evaluation of the response of d-limonene to the antioxidant enzymes SOD and CAT its antioxidant capacity (FRAP) and action on the anti and pro-apoptotic proteins by immunofluorescence and Western Blotting techniques. Values of probability of p <0.05 were considered statistically significant. All data were expressed as mean ± Standard Mean Error (SEM), and the number of animals 5-6 per group. The results showed that d-limonene prevented ST segment elevation in 30% of the evaluated animals, prevented the increase of the QTc (71,66 ± 6,604 from 102,9 ± 5,04) and FC (332,7 ± 20,96 from 500,6 ± 13,69 bpm) interval, reduced the infarct area to 8.34%, and prevented histological changes in muscle fibers as well as decreased mononuclear cell infiltration, decreased oxidative stress by decreasing the ROS, restoring the SOD activity to values close to the control (24.35 ± 3.87 U/mg), to decrease the sulfidrylation, carbonylation and lipid peroxidation, and suppressed proapoptotic by reducing the expression of Bax and the activation of pro-caspase 3 to parameters equal to the control (93,54 ± 3,15 e 100 ± 2,37, respectively). Thus, the pharmacological findings of d-limonene converge to decrease the pro-apoptotic effect by reducing pro-apoptotic enzymes, reducing the infarct area, and producing ROS and increasing SOD activity.
publishDate 2019
dc.date.issued.fl_str_mv 2019-07-24
dc.date.accessioned.fl_str_mv 2021-01-06T18:55:30Z
dc.date.available.fl_str_mv 2021-01-06T18:55:30Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv DURÇO, Aimée Obolari. Efeito cardioprotetor do d-limoneno sobre o infarto agudo do miocárdio em modelo animal. 2019. Dissertação (Mestrado em Ciências Aplicadas à Saúde) - Universidade Federal de Sergipe, Lagarto, 2019.
dc.identifier.uri.fl_str_mv https://ri.ufs.br/jspui/handle/riufs/13884
identifier_str_mv DURÇO, Aimée Obolari. Efeito cardioprotetor do d-limoneno sobre o infarto agudo do miocárdio em modelo animal. 2019. Dissertação (Mestrado em Ciências Aplicadas à Saúde) - Universidade Federal de Sergipe, Lagarto, 2019.
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