Influence of cajá supplementation on cardiac remodeling induced by cigarette smoke exposure in rats

Author(s)

Maria Angélica Martins Lourenço

• Document type: Master's Dissertation
• Press: Botucatu. 2017-04-12.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu
• Defense date: 2017-02-14
• Advisor: Marcos Ferreira Minicucci; Paula Schmidt Azevedo Gaiolla

Abstract

Introduction: The effects of exposure to tobacco smoke (ETS) on the vascular system are widely known, however, recent studies showed that this exposure results in direct myocardial effects leading to cardiac remodeling (CR). Due to the high socioeconomic impact and the high mortality rates, it is relevant to identify factors that modulate the CR process and we can highlight the supplementation of foods with antioxidant properties, such as cajá (Spondias mombin). Objective: The objective of this study is to evaluate the influence of cajá supplementation on the cardiac remodeling process induced by ETS in rats. Materials and methods: The study was carried out in two stages. In the first stage, three groups not exposed to tobacco smoke were studied: C0 (control + standard chow); C100 (control + cajá 100 mg / kg of body weight / day); C250 (control + cajá 250 mg / kg of body weight / day). After two months of supplementation the animals were submitted to an echocardiogram. In the second step, considering that there was no difference in the comparison between C0, C100 and C250, the analyzes were performed with the following groups: C0 (control + standard chow); F0 (smoke + standard chow); F100 (smoke + cajá 100 mg / kg body weight / day) and F250 (smoke + cajá 250 mg / kg body weight / day). The cajá supplementation was carried out with the peel and pulp of the fruit homogenized and added in the standard chow. After 2 months of supplementation, a functional, morphometric and biochemical study was performed. For the parametric variables, we used one-way ANOVA test followed by Tukey's post-test and the values obtained were presented as mean ± standard deviation. For the nonparametric variables, the Kruskal-Wallis test followed by Dunn´s post-test was performed and the values obtained were presented as median and interquartile range. The variables were considered non-parametric when they did not pass the Kolmogorov-Smirnov normality test. The level of significance was 5%. Results: Smokers (F0, F100 and F250) presented lower chow intake and final body weight (BW) than control animals (C0). Considering the serum cotinine dosage, the smoked animals presented higher concentration in comparison to the control animals. However, in the comparison between smoking groups there was no statistically significant difference. The ETS induced morphological and morphometric changes in the left ventricle (LV), as seen by the higher values of left ventricular diastolic and systolic diameter adjusted by BW (LVDD/BW and LVSD/BW, respectively), area and diameter of the left atrium adjusted by BW (area AL and AL/BW, respectively) LV mass index, LV weight adjusted by BW and myocardial sectional area (MSA) in relation to control animals. On the other hand, animals supplemented with cajá at 250 mg / kg of body weight / day presented lower values of, LVDD/BW, area AL and MSA compared to group F0. There was no statistically significant difference for the variables of the isolated heart study. In relation to oxidative stress, the F0 group had a higher lipid hydroperoxide (LH) concentration compared to the C0 group, and animals supplemented with 100 and 250 mg / kg body weight / day presented lower values when compared to the group F0. Smokers had lower values of catalase activity (CAT) compared to control animals. The F0 group had a lower value of superoxide dismutase activity (SOD) compared to the C0 group and the animals supplemented with cajá at 100 and 250 mg / kg of body weight / day had higher values of SOD activity compared to the group F0 . Smokers had a lower value of glutathione peroxidase (GSH-Px) activity compared to the C0 group, and animals supplemented with cajá at 100 and 250 mg / kg of body weight / day showed higher values of GSH-Px activity in comparison with the F0 group. No statistically significant differences were observed in the carbonyl protein concentration and in the comet test both in relation to the effect of the ETS and the supplementation of cajá. In relation to the energetic metabolism, the F0 group had lower activity value of the enzyme ß-hydroxyacyl Coenzyme A dehydrogenase (ß-OH Acyl CoA-DH) when compared to the C0 group. The F100 group presented higher values of ß-OH Acyl CoA-DH compared to the F0 group. Considering the activity of phosphofructokinase (PFK) and lactate dehydrogenase (LDH), the F0 and F100 groups showed higher activity of these enzymes compared to the C0 group. The F250 group, on the other hand, had lower PFK and LDH activity compared to the F0 and F100 groups. No statistically significant differences were observed in relation to pyruvate dehydrogenase (PDH) activity. The smoking groups had lower values regarding citrate synthase activity (CS) compared to the C0 group. In addition, the F250 group had higher CS values than the F0 group. In relation to the complex I, the smoking groups obtained lower values when compared to the group C0 and the group F250 presented highervalues in relation to the group F0 and the group F100. Considering the analysis of the activity of the complex II, the groups F0 and F100 presented smaller values when compared to the group C0 and the group F250 presented higher values in relation to the groups F0 and F100. Regarding ATP synthase activity, the smoking groups had lower values in comparison to the C0 group. No significant differences were observed in protein expression of erythroid-2 nuclear factor (NRF-2), sirtuin 1 (SIRT-1), total nuclear-kB factor (NFkB), nuclear kB factor phosphorylated (pNFkB), NFkB / pNFkB, interleukin 10 (IL-10), gamma interferon (IFN-γ), type I and type III collagen. Conclusion: ETS resulted in CR, worsening oxidative stress, and altered cardiac metabolism. Cajá supplementation attenuated the cardiac remodeling process, improved oxidative stress, and changes in energetic metabolism induced by ETS in rats. (AU)

• FAPESP's process: 14/21310-0 - Influence of caja supplementation on cardiac remodeling induced by cigarette smoke exposure in rats
• Grantee: Maria Angelica Martins Lourenço
• Support Opportunities: Scholarships in Brazil - Master