Influência da suplementação de acerola (Malpighia emarginata) sobre a remodelação cardíaca em ratos submetidos a infarto do miocárdio
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Data
2021-07-30
Autores
Damasceno, Barbara Catalano [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
As doenças cardiovasculares são importante problema de saúde em nossa sociedade, sendo o infarto do miocárdio (IM) a primeira causa de morte no Brasil. Após IM mudanças complexas ocorrem no ventrículo esquerdo (VE), que são definidas como remodelação cardíaca (RC). Vários fatores podem participar nas adaptações da RC após o IM, como estresse oxidativo, inflamação, apoptose, além de fibrose, que ocorre por alterações da matriz extracelular (ME). Sendo assim, estratégias para atenuar a RC após o IM podem diminuir ainda mais a mortalidade pós-IM e limitar a morbidade. Neste contexto, compostos bioativos (CBAs) de produtos naturais, com propriedades cardioprotetoras como flavonoides podem ser um importante adjuvante na terapia do IM. A vitamina C é um CBA importante para a saúde humana, pois é fundamental para diversas atividades fisiológicas como síntese de colágeno, além de atuar como poderoso antioxidante. Estudos experimentais e clínicos realizados com infarto e suplementação de VC mostraram que a suplementação de VC diminui a hipertrofia e melhora a função cardíaca pós-IM, e exerce papel antioxidante e antiinflamatório. Adicionalmente, estudo com deficiência de VC mostrou risco aumentado de IM e piora da função sistólica e diastólica, sendo de extrema importância para sobrevivência pós-I M. A acerola, é uma fruta com altíssimos teores de vitamina C e outros compostos bioativos com potencial antioxidante que mostram-se eficazes no tratamento adjuvante do IM. Sendo assim, a vitamina C e os CBAs podem ter importante papel no tratamento do infarto do miocárdio, atenuando a remodelação cardíaca pós-infarto. Além disso, a interação entre vitamina C e os CBAs da acerola podem exercer ação sinérgica, potencializando os efeitos benéficos, comparado à suplementação isolada de cada composto separadamente. Sendo assim, o objetivo do estudo foi verificar a influência da suplementação de vitamina C e da acerola sobre a remodelação cardíaca após infarto do miocárdio em ratos. Para este estudo foram utilizados ratos machos da raça Wistar, divididos em 3 grupos: 1) grupo infarto (I), animais submetidos ao infarto experimental e alimentados com dieta padrão; grupo infarto e vitamina C (IVC), animais submetidos ao infarto experimental e alimentados com ração suplementada com vitamina C (150mg/kg); grupo infarto e acerola (IA), animais submetidos ao infarto experimental e alimentados com ração suplementada com acerola (15g/kg). A quantidade de acerola suplementada forneceu a mesma quantidade de vitamina C que receberam os grupos suplementados apenas com esta vitamina hidrossolúvel. Após três meses, esses animais foram submetidos à avaliação ecocardiográfica e posteriormente à eutanásia, onde foi realizada a coleta de material biológico pararealização das análises histológicas, bioquímicas e moleculares. Pela análise histológica foram excluídos os infartos inferiores a 30%, restando 15 animais 5 no grupo I, 15 animais no grupo IVC e 16 animais no grupo IA. Para análise estatística foi utilizada ANOVA de 1 via (dados apresentados em média ± DP) ou Kruskal Wlallis (dados apresentados em mediana e percentil 25 e 75), de acordo com a normalidade dos dados, e o valor de p foi de 5%. Não houve diferença entre os grupos para o peso corporal, final e para a ingestão de ração. Com relação às alterações estruturais podemos observar diminuição do AE e do DSVE nos animais IVC e IA comparados ao I. O AE/AO foi menor e a ESSV foi maior apenas no IA comparado ao I. Com relação às variáveis de função sistólica, houve aumento da FE e da % de encurtamento endocárdico em IVC e IA comparados ao I, e maior VEPP e menor IPM no IA comparado ao I. Para a análise de função diastólica podemos observar maiores valores de E'médio no IA comparado ao I, e maiores valores da relação E’/A’ também no grupo IA, quando comparado ao I e ao IVC. Não houve diferença estatisticamente significante entre os grupos para nenhuma variável morfométrica analisada, nem para as análises histológicas de área do infarto e porcentagem de colágeno total. Para os parâmetros de estresse oxidativo, DHE e expressão das proteínas antioxidantes GPx e HO-1, também não foram observadas diferenças. Para os mediadores inflamatórios, houve maiores valores de IL-10 no grupo IA quando comparado ao grupo I. Com relação aos componentes de matriz extracelular, houve diminuição do colágeno III e do TIMP-2 em ambos os grupos suplementados; diminuição do colágeno I apenas no grupo IVC; e diminuição do TIMP-4 apenas no grupo IA. Podemos concluir que a suplementação de vitamina C e acerola atenuam remodelação cardíaca pós IM, com melhora da função sistólica e diastólica. Os mecanismos envolvidos podem ser decorrentes da remodelação da matriz extracelular e do aumento da citocina anti-inflamatória IL-10.
Cardiovascular diseases are an important health problem in our society, with myocardial infarction (MI) being the leading cause of death in Brazil. After MI complex changes occur in the left ventricle (LV), which are defined as cardiac remodeling (CR). Several factors can participate in CR adaptations after MI, such as oxidative stress, inflammation, apoptosis, in addition to fibrosis, which occurs due to changes in the extracellular matrix (EM). Thus, strategies to attenuate CR after MI can further reduce post-MI mortality and limit morbidity. In this context, bioactive compounds (BCAs) from natural products with cardioprotective properties such as flavonoids can be an important adjuvant in MI therapy. Vitamin C is an important BCA for human health, as it is essential for various physiological activities such as collagen synthesis, in addition to acting as a powerful antioxidant. Experimental and clinical studies performed with infarction and VC supplementation showed that VC supplementation decreases hypertrophy and improves post-MI cardiac function, and plays an antioxidant and anti-inflammatory role. Additionally, a study with VC deficiency showed an increased risk of MI and worsening of systolic and diastolic function, being extremely important for post-IM survival. Acerola is a fruit with very high levels of vitamin C and other bioactive compounds with antioxidant potential which are effective in the adjuvant treatment of MI. Thus, vitamin C and CBAs may play an important role in the treatment of myocardial infarction, attenuating post-infarction cardiac remodeling. Furthermore, the interaction between vitamin C and acerola CBAs can exert synergistic action, enhancing the beneficial effects, compared to the isolated supplementation of each compound separately. Thus, the study aimed to verify the influence of vitamin C and acerola supplementation on cardiac remodeling after myocardial infarction in rats. For this study, male Wistar rats were used, divided into 3 groups: 1) infarction group (I), animals submitted to experimental infarction and fed a standard diet; infarction and vitamin C group (IVC), animals submitted to experimental infarction and fed with a diet supplemented with vitamin C (150mg/kg); infarction and acerola group (AI), animals submitted to experimental infarction and fed with a diet supplemented with acerola (15g/kg). The amount of acerola supplemented provided the same amount of vitamin C that the groups supplemented with only this water-soluble vitamin received. After three months, these animals were submitted to echocardiographic evaluation and later to euthanasia, where biological material was collected for performing histological, biochemical, and molecular analyses. By histological analysis, infarcts below 30% were excluded, leaving 15 animals in group I, 15 animals in group IVC, and 16 animals in group IA. For statistical analysis, 1-way ANOVA (data presented in mean ± 7 SD) or Kruskal Wallis (data presented in median and 25th and 75th percentile) was used, according to the normality of the data, and the p-value was 5%. There was no difference between groups for body weight, final, and feed intake. Regarding structural changes, we can observe a decrease in LA and LVSD in IVC and IA compared to I. The LA/AO was smaller and the ESSV was higher only in the IA compared to the I. Regarding the systolic function variables, there was an increase of EF and % of endocardial shortening in CVI and IA compared to I, and higher VEPP and lower MPI in IA compared to I. For the analysis of diastolic function, we can observe higher E'mean values in IA compared to I, and higher values of the E'/A' ratio also in the IA group, when compared to the I and the IVC. There was no statistically significant difference between groups for any morphometric variable analyzed, nor for the histological analysis of infarct area and percentage of total collagen. For the parameters of oxidative stress, DHE, and expression of antioxidant proteins GPx and HO-1, no differences were observed either. For inflammatory mediators, there were higher values of IL-10 in group IA when compared to group I. Regarding extracellular matrix components, there was a decrease in collagen III and TIMP-2 in both supplemented groups; decreased collagen I only in the IVC group, and decreased TIMP-4 only in the IA group. We can conclude that vitamin C and acerola supplementation attenuate post-MI cardiac remodeling, with improvement in systolic and diastolic function. The mechanisms involved may result from the remodeling of the extracellular matrix and the increase in the anti-inflammatory cytokine IL-10.
Cardiovascular diseases are an important health problem in our society, with myocardial infarction (MI) being the leading cause of death in Brazil. After MI complex changes occur in the left ventricle (LV), which are defined as cardiac remodeling (CR). Several factors can participate in CR adaptations after MI, such as oxidative stress, inflammation, apoptosis, in addition to fibrosis, which occurs due to changes in the extracellular matrix (EM). Thus, strategies to attenuate CR after MI can further reduce post-MI mortality and limit morbidity. In this context, bioactive compounds (BCAs) from natural products with cardioprotective properties such as flavonoids can be an important adjuvant in MI therapy. Vitamin C is an important BCA for human health, as it is essential for various physiological activities such as collagen synthesis, in addition to acting as a powerful antioxidant. Experimental and clinical studies performed with infarction and VC supplementation showed that VC supplementation decreases hypertrophy and improves post-MI cardiac function, and plays an antioxidant and anti-inflammatory role. Additionally, a study with VC deficiency showed an increased risk of MI and worsening of systolic and diastolic function, being extremely important for post-IM survival. Acerola is a fruit with very high levels of vitamin C and other bioactive compounds with antioxidant potential which are effective in the adjuvant treatment of MI. Thus, vitamin C and CBAs may play an important role in the treatment of myocardial infarction, attenuating post-infarction cardiac remodeling. Furthermore, the interaction between vitamin C and acerola CBAs can exert synergistic action, enhancing the beneficial effects, compared to the isolated supplementation of each compound separately. Thus, the study aimed to verify the influence of vitamin C and acerola supplementation on cardiac remodeling after myocardial infarction in rats. For this study, male Wistar rats were used, divided into 3 groups: 1) infarction group (I), animals submitted to experimental infarction and fed a standard diet; infarction and vitamin C group (IVC), animals submitted to experimental infarction and fed with a diet supplemented with vitamin C (150mg/kg); infarction and acerola group (AI), animals submitted to experimental infarction and fed with a diet supplemented with acerola (15g/kg). The amount of acerola supplemented provided the same amount of vitamin C that the groups supplemented with only this water-soluble vitamin received. After three months, these animals were submitted to echocardiographic evaluation and later to euthanasia, where biological material was collected for performing histological, biochemical, and molecular analyses. By histological analysis, infarcts below 30% were excluded, leaving 15 animals in group I, 15 animals in group IVC, and 16 animals in group IA. For statistical analysis, 1-way ANOVA (data presented in mean ± 7 SD) or Kruskal Wallis (data presented in median and 25th and 75th percentile) was used, according to the normality of the data, and the p-value was 5%. There was no difference between groups for body weight, final, and feed intake. Regarding structural changes, we can observe a decrease in LA and LVSD in IVC and IA compared to I. The LA/AO was smaller and the ESSV was higher only in the IA compared to the I. Regarding the systolic function variables, there was an increase of EF and % of endocardial shortening in CVI and IA compared to I, and higher VEPP and lower MPI in IA compared to I. For the analysis of diastolic function, we can observe higher E'mean values in IA compared to I, and higher values of the E'/A' ratio also in the IA group, when compared to the I and the IVC. There was no statistically significant difference between groups for any morphometric variable analyzed, nor for the histological analysis of infarct area and percentage of total collagen. For the parameters of oxidative stress, DHE, and expression of antioxidant proteins GPx and HO-1, no differences were observed either. For inflammatory mediators, there were higher values of IL-10 in group IA when compared to group I. Regarding extracellular matrix components, there was a decrease in collagen III and TIMP-2 in both supplemented groups; decreased collagen I only in the IVC group, and decreased TIMP-4 only in the IA group. We can conclude that vitamin C and acerola supplementation attenuate post-MI cardiac remodeling, with improvement in systolic and diastolic function. The mechanisms involved may result from the remodeling of the extracellular matrix and the increase in the anti-inflammatory cytokine IL-10.
Descrição
Palavras-chave
Infarto do miocardio, Acerola, Remodelação cardiaca, Vitamina C, Suplementação