RESSALVA 

Atendendo solicitação do(a) 
autor(a), o texto completo desta 
dissertação será disponibilizado 
somente a partir de 28/02/2022. 



UNIVERSIDADE ESTADUAL PAULISTA “JÚLIO DE 

MESQUITA FILHO” 

PRISCILA MANFIO QUEIROZ 

IMPACTO DA DIETA HIPERCALÓRICA NO TECIDO CARDÍACO E DA 

SUPLEMENTAÇÃO COM NARINGENINA:  PARÂMETROS 

METABÓLICOS E ESTRESSE OXIDATIVO 

Dissertação apresentada à Faculdade de 

Medicina, Universidade Estadual Paulista 

“Júlio de Mesquita Filho”, Campus de 

Botucatu, para obtenção do título de Mestre 

em Fisiopatologia em Clínica Médica. 

Orientadora: Profa. Dra. Ana Angélica 

Henrique Fernandes  

BOTUCATU 

2018 



  

 
 

 

 

 

PRISCILA MANFIO QUEIROZ 

 

 

 

 

Impacto da dieta hipercalórica no tecido cardíaco e da 

suplementação com naringenina:  parâmetros metabólicos 

e estresse oxidativo 

 

Dissertação apresentada à Faculdade de 

Medicina, Universidade Estadual Paulista 

“Júlio de Mesquita Filho”, Campus de 

Botucatu, para obtenção do título de Mestre 

em Fisiopatologia em Clínica Médica. 

 

 

Orientadora: Profa. Dra. Ana Angélica 

Henrique Fernandes  

 

 

 

 

 

 

 

 

Botucatu 

2018 



  

 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



  

 
 

 

 

 

 

 

 

 

 

 
 

 “Quando tudo tiver parecendo ir contra você, lembre-se que o avião decola 

contra o vento, e não a favor dele”. 

                                                                                                  Henry Ford 

  



  

 
 

DEDICATÓRIA  

 

Dedico este trabalho aos meus pais Luiz Carlos Queiroz e Silvia Raquel Manfio 

Queiroz, sem a paciência, compreensão, e o total apoio durante toda a minha jornada 

de estudos nada seria possível.     

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



  

 
 

AGRADECIMENTOS 

 

À minha orientadora Ana Angélica Henrique Fernandes sempre muito 

atenciosa, presente e paciente. Obrigado pelos ensinamentos e pela confiança em me 

dar essa oportunidade.  

Ao técnico do biotério do Departamento de Bioquímica Fábio pelo auxílio no 

manejo dos animais. 

À equipe do laboratório Lucas, Anderson, Pedro, Barbara, Mariana e Nagilla, 

por toda colaboração quando precisei e troca de conhecimento.  

Aos meus amigos pelo companheirismo, dividir momentos bons e ruins, 

conselhos, auxílio e dedicação em me ajudar em momentos com dificuldade.         

Aos funcionários da Unidade de Pesquisa Experimental pelo auxílio nas 

atividades do dietário. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



  

 
 

RESUMO 

 

Introdução: A dieta ocidental rica em carboidrato e lipídio promove o desenvolvimento 

da síndrome metabólica. Alterações do metabolismo energético provocadas por um 

desbalanço redox em virtude de dieta hipercalórica, gera danos oxidativos e 

deficiência no sistema enzimático antioxidante, intensificando fatores de risco e 

eventos que levam à doença cardiovascular. Os flavonoides são compostos de origem 

vegetal com propriedades antioxidante e antiaterogênico. O objetivo do estudo foi 

avaliar as alterações metabólicas séricas e cardíacas em ratos submetidos a dieta 

hipercalórica e tratados com naringenina. Material e Métodos: Foram utilizados 32 

ratos Wistar machos, distribuídos em 4 grupos: (C) Controle, (N) naringenina, (H) 

hipercalórico, (HN) hipercalórico tratado com naringenina. Os grupos (C e N, n=16) 

receberam dieta padrão enquanto que os grupos (H e HN, n=16) receberam dieta 

hipercalórica durante 30 dias. Após este período iniciou-se o tratamento com 

naringenina 50mg/kg (grupos N e HN) durante 43 dias à intervalos de 7 dias via intra 

gástrica. Ao final do experimento, os animais foram anestesiados para eutanásia. 

Foram coletadas duas porções de tecido cardíaco e amostra sérica para análise de 

perfil lipídico, glicemia, metabolismo energético, estresse oxidativo e glicogênio 

cardíaco. Resultados: O grupo (HN) tiveram uma diminuição na ingestão hídrica e 

ingestão alimentar, peso final, ganho de peso e glicemia. Não houve diferença 

significativa no peso inicial entre os grupos. Houve uma melhora no grupo (HN) no 

perfil lipídico, metabolismo energético e estresse oxidativo com exceção do glicogênio, 

proteínas totais, e atividade da catalase que não apresentaram diferença significante. 

Conclusão: O consumo de dieta hipercalórica causou dislipidemia, hiperglicemia, 

prejudicou o metabolismo energético e provocou consequentemente o estresse 

oxidativo no miocárdio. A análise da glicemia e perfil lipídico demonstrou que a 

suplementação de naringenina foi eficiente em atenuar esses parâmetros em animais 

submetidos à dieta hipercalórica.  A oxidação exacerbada de ácidos graxos e o 

estresse oxidativo no tecido cardíaco, provocados pela dieta hipercalórica, foram 

controlados pela administração de naringenina.  

 

Palavras-chave: Naringenina, Dieta hipercalórica, Metabolismo energético, Estresse 

oxidativo  



  

 
 

 

ABSTRACT 

 

Introduction: Western diet rich in carbohydrates and lipids is an important role in 

metabolic syndrome development.  Energy metabolism alterations caused by redox 

unbalance due to high fat diet, generated oxidative damage and deficiency in the 

antioxidant enzyme system, increasing risk factors and events that lead to 

cardiovascular disease. Flavonoids are natural compounds with antioxidant and 

antiatherogenic properties. This study assessed serum and cardiac metabolic 

alterations in rats fed with high fat diet and treated with naringenin. Material and 

Methods: We used 32 male Wistar rats, divided into 4 groups: (C) control, (N) 

naringenin, (H) high fat diet, (HN) high fat diet treated with naringenin. Groups (C and 

N, n=16) received standard diet whereas the groups (H and HN, n=16) received high 

fat diet during 30 days. After this period, the rats were treated with naringenin 50mg/kg 

(groups N and HN) during 43 days and at 7 days interval by gavage. Animals were 

anesthetized and led to euthanasia. Two cardiac tissue portions were collected as well 

as blood serum to evaluate lipid profile, glycemia, energy metabolism, oxidative stress 

and cardiac glycogen. Results: Group (HN) showed a decreased in water and food 

intake, final body weight, body weight gain and glycemia. There wasn’t significant 

difference in initial body weight between the groups. There was an improvement in 

group (HN) on lipid profile, energy metabolism and oxidative stress. There wasn’t 

significant difference on catalase activity, cardiac glycogen and total protein. 

Conclusion: It was concluded that high fat diet ingestion lead to dyslipidemia, 

hiperglycemia, empaired energy metabolism and caused oxidative stress in 

myocadium. Glycemic analysis and lipid profile showed that the supplementation of 

naringenin was effective to reduce these parameters in animals induced to high fat 

diet. The exacerbated oxidation of fatty acids and the oxidative stress in the cardiac 

tissue induced by high fat diet were controlled by naringenin administration.   

Keywords: Naringenin, High fat diet, Energy metabolism, Oxidative stress 



  

 
 

 

 

LISTA DE TABELAS 

 

Tabela 1 – Resultados médios obtidos para ingestão hídrica (ml/dia), ingestão 
alimentar (g/dia), peso inicial (g), peso final (g), ganho de peso (g) e glicemia 
nos diferentes grupos experimentais................................................................... 31 

 

Tabela 2 -  Resultados médios obtidos para a concentração sérica de colesterol 
total (CT), LDL-colesterol (LDL-c), triacilgliceróis (TG), VLDL-colesterol (VLDL-
c) e HDL-colesterol (HDL-c) para os diferentes grupos 
experimentais....................................................................................................... 32 

 
Tabela 3– Resultados médios obtidos para a atividade da lactato 
desidrogenase (LDH), citrato sintase (CS) e β-hidroxi acil CoA-desidrogenase 
(OHADH) no tecido cardíaco para os diferentes grupos 
experimentais....................................................................................................... 34 

 
Tabela 4– Resultados médios obtidos para concentração de glicogênio e 
proteínas totais no tecido cardíaco para os diferentes grupos experimentais..... 36 

 
Tabela 5 – Resultados médios obtidos para concentração de hidroperóxido de 
lipídio (HP), atividade da catalase (CAT), superóxido dismutase (SOD) e da 
glutationa peroxidase (GSH-Px) no tecido cardíaco para os diferentes grupos 
experimentais....................................................................................................... 37 

 

 

 

 

 

 

 

 

 



  

 
 

LISTA DE FIGURAS 

 

Figura 1 – Geração e degradação de espécies reativas .................................... 15 

Figura 2 – Desbalanço energético na insuficiência cardíaca ............................. 17 

Figura 3 – Estrutura química dos flavonoides .................................................... 19 

Figura 4 – Resumo do efeito do flavonoide cítrico no metabolismo do modelo 
animal .................................................................................................................. 22 

Figura 5 – Delineamento experimental ............................................................... 25 

Figura 6 – Resultados médios obtidos para a concentração da glicemia sérica 
nos diferentes grupos experimentais .................................................................. 31 

Figura 7 – Resultados médios obtidos para a concentração sérica de CT (A), 
LDL-colesterol (B), TG (C), VLDL-colesterol (D) e HDL-colesterol (E) para os 
diferentes grupos experimentais ......................................................................... 

33 

 
Figura 8 – Resultados médios obtidos para a atividade de LDH (A), CS (B) e 
OHADH (C) para os diferentes grupos experimentais ........................................ 

35 

 
Figura 9 – Resultados médios obtidos para a concentração de glicogênio (A) 
e Pt (B) no tecido cardíaco para os diferentes grupos experimentais ................. 

36 

 
Figura 10 – Resultados médios obtidos para a concentração de HP (A), 
atividade da CAT (B), SOD (C) e da GSH-Px (C) para os diferentes grupos 
experimentais ...................................................................................................... 

38 

 

 

 

 

 

 

 

  



Sumário 

RESUMO 

ABSTRACT 

LISTA DE TABELAS 

LISTA DE FIGURAS 

INTRODUÇÃO .......................................................................................................... 11 

HIPÓTESE ................................................................................................................ 23 

OBJETIVO GERAL ................................................................................................... 23 

OBJETIVOS ESPECÍFICOS ..................................................................................... 23 

MATERIAIS E MÉTODOS ......................................................................................... 24 

RESULTADOS .......................................................................................................... 31 

DISCUSSÃO ............................................................................................................. 40 

CONCLUSÕES ......................................................................................................... 56 

REFERÊNCIAS BIBLIOGRÁFICAS .......................................................................... 57 



  

56 
 

CONCLUSÕES 

 

Conclui-se que o consumo de dieta hipercalórica causou dislipidemia, 

hiperglicemia, prejudicou o metabolismo energético e provocou consequentemente 

estresse oxidativo no miocárdio. A análise da glicemia e perfil lipídico demonstrou que 

a suplementação de naringenina foi eficiente em atenuar esses parâmetros em 

animais submetidos à dieta hipercalórica.  A oxidação exacerbada de ácidos graxos e 

o estresse oxidativo no tecido cardíaco, provocados pela dieta hipercalórica, foram 

controlados pela administração de naringenina.  

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



  

57 
 

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