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EO e Inflamação na DCV:

um estado de mal adaptação!

Vanessa dos Santos Pereira Montera


Pós graduada em Nutrição Clínica Funcional
Pós graduada em Fitoterapia Funcional
Mestre em Ciências Cardiovasculares - UFF
Doutoranda em Saúde Coletiva – UERJ
Estresse Oxidativo
Estresse Oxidativo
Estresse Oxidativo e Inflamação

Antioxid. Redox Signal ; 2011


Formação Placa Ateroma

Monocyte Vessel Lumen


LDL

Adhesion Endothelium
MCP-1
Molecules LDL
Intima
Modified
Cytokines LDL Growth Factors
Metalloproteinases

Cell Proliferation
Macrophage
Foam Cell Matrix Degradation

Ross R. N Engl J Med. 1999;340:115-126. 5


Complicação Placa Ateroma

Colocar foto 41.15 pg 885

J Intern Med 263:517,62008


8] (Figure 6A). Thus, basal autophagy and a mild regulation of autophagy, Sirt1 may activate autophag
ive autophagy response may exert protective by deacetylating FOXO1 and FOXO3 [96, 97, 98, 99

Aterosclerose x Autofagia
ts against cellular stresses such as inflammation
xidative stress, leading to delays in vascular aging
in the nucleus (Figure 6C and D). In the cytosol, Sirt
targets Atg5, Atg7, and Atg8 (which are autophagy pro

7
AGING 2016, Vol. 8, No. 10
Inflamação na DCV

Qual tipo de
Inflamação inflamação estamos falando?
Aguda:
- Término do recrutamento de céls inflamatórias
Inflamação
- Remoção dasAguda ≠ Inflamação
céls inflamatórias Crônica
por apoptose
- Reprogramação dos macrófagos para um
fenótipo anti- inflamatório e regenerativo
- Egresso das céls efetoras
- Regeneração do tecido

Atherosclerosis – A matter of unresolved inflammation. Semin Immunol 2015


Inflamação na DCV
Falência da Fase de Resolução

Mal Adaptação

Ativação i. inata e adaptativa

Início, progressão e consequências clínicas da


DCV

Atherosclerosis – A matter of unresolved inflammation. Semin Immunol 2015


Inflamação na DCV
Insulto inicial
ao endotélio LDL-c

LDL-modificada Linf T
CD4+Th1

ITFγ + TNFα

Bloqueia síntese
colágeno

International Journal of Cardiology 221 (2016) 581–586


Risco Inflamatório Residual

43% RIR 47%RIR 61% RIR


27% RCR 28% RCR 70% RCR

11
Circ Res. 2017;120:617-619
ndivíduos sem distúrbios de Sono !

Sono de 8 para 6 horas

sultado:
IL-6 40 a 60%
!

" " " " TNF- 20 a 30%


POLUIÇÃO
Vgontzas AN et al. J Clin Endocrinol Metab 2004, 89:2119-26. !

12
HÁBITOS ALIMENTARES
X ÓBITOS POR DCV

- Excesso de ingestão de sódio (9,5%)


- Baixa ingestão de nozes/sementes (8,5%)
- Alta ingestão de carnes processadas (8,2%)
- Baixo teor de ácidos graxos ômega-3 (7,8%)
- Baixa ingestão de hortaliças (7,6%) e frutas (7,5%)
- Consumo de bebidas com alto teor de açúcares (7,4%)
- Baixa ingestão de grãos integrais (5,9%) e gorduras poli-insaturadas (2,3%)
- Alta ingestão de carnes vermelhas não processadas (0,4%)

EUA (2012): 45,4% dos óbitos por DCV

JAMA. 2017;317(9):912-924
4
Dieta Anti-Inflamatória Nutrition in Clinical Practice XX(X)

Table 1. Comparison of Diet Components.

Diet Standard American Diet Mediterranean Diet Okinawan Diet Anti-Inflammatory Diet
Vegetables Fewer vegetables High consumption High consumption of High consumption of vegetables:
and fruits of vegetables and vegetables: orange- large diversity, including
fruits yellow root vegetables, variety of colors to increase
leafy green vegetables phytonutrients
Protein source Red meat Fish High consumption of Plant sources of protein: legumes,
legumes (soy) soy, nuts, and seeds
Dairy Legumes Small to moderate More fatty fish and some lean
amounts of fish animal protein
Nuts Less meat
Carbohydrates Refined carbohydrates; Whole grains Small amounts of rice and Whole grains in small amounts,
high-fructose corn noodles high fiber, reduced refined
syrup and added sugar Less sugar and fewer carbohydrates
Fewer whole grains refined grains

Dairy High-fat dairy sources Low-fat dairy, such Less dairy


as yogurt
Fats Solid added fats, such as Olive oil as source of Lower fat overall Olive oil for added fat source
butter and sour cream added fat
Other features Soda and added-sugar Moderate red wine Moderate alcohol intake, Spices: turmeric, garlic, ginger,
beverages intake green tea intake; broth- and other anti-inflammatory
based soups herbs and spices
Cultural Eating on the run, Highly social and Low caloric diet; highly Mindful eating approach; quality
overeating connected eating ritualistic culture over quantity
experiences

Nutr Clin Pract 2017


Dieta Anti-Inflamatória
Dieta Inflamação x Anti-inflamação
Kcal Excesso: > adiposidade > inflamação
Redução Kcal + adequada ingestão nutriente =  Glicose/ insulina/ AGE -
-- quimiocinas, EO, citocinas inflamatórias
Cho Refinados e alta CG: RL, marcadores inflam, glicose, insulina (estimula
delta-5 e delta-6 dessaturase)
Fontes: principalmente - vegetais e frutas (+veg) orgânicos
cereais integrais
Ptn Primariamente vegetal (soja orgânica, cogumelos) + algumas porções de
peixes selvagens, carne magra e leite ---orgânicos
Atenção ao método de cozinhar: AH, AGE, HAP
Gorduras W6/W3<5
Sem AGG trans (sem GI)
Polifenóis Vinho com moderação
Chás
Ervas e especiarias

Nutr Clin Pract 2017


Índice Inflamatório Dieta

161265
Int. J. Mol. Sci. 2016, 17,
Dieta do Mediterrâneo

Figure 2. Effects of the Traditional Mediterranean Diet enriched with virgin olive oil (TMD-
Figure 4. Effects of the Traditio
VOO) or nuts (TMD-Nuts), relative to a low-fat diet, on the resistance of LDL particles

VOO) or nuts (TMD-Nuts), rela


against oxidation (LDL lag time) (A-B) and LDL oxidation (C-D).
Mol Nutr A,C.
FoodPost- vs. pre-
Res. 2017 Sep;61(9)
Dieta DASH x PCR

Clin Nutr 17 Feb 2017


AGP x Inflamação

19
Inibição COX-2 Ervas e Especiarias

RE= alecrim SE= sálvia BLE= louro GE= gengibre TE= tuméricos

Misturas: RTE, BLSE, SGE, BLTE


Nutrients 2017, 9, 1051
Inibição COX-2 Ervas e Especiarias

RE= alecrim SE= sálvia BLE= louro GE= gengibre TE= tuméricos

Misturas: RTE, BLSE, SGE, BLTE


Nutrients 2017, 9, 1051
Fontes de Quercetina:

- Cebola roxa
- Maçã
- Uva Roxa
- Berries
- Brócolis
- Salsa
Antocianinas x Quimiocinas
Plaquetárias

Nutrition & Metabolism (2016) 13:86


Antocianinas x Quimiocinas
Plaquetárias

Nutrition & Metabolism (2016) 13:86


Antocianinas nas “Berries” do Brasil

Acerola (16,0 mg/100 g) Açaí (97mg/100g) Jabuticaba (29mg/100g)

Pitanga roxa (410mg/100g) Ciriguela (16,4mg/100g) Jambolão (111,2mg/100g)


Favaro, MMA; Dissertação de Mestrado, IQ-UNICAMP, Campinas, 2008.
Embrapa. Boletim de Pesquisa e Desenvolvimento, Belém – Pará, dez 2006.
Vizzoto M et al. V Encontro Sobre Pequenas Frutas E Frutas Nativas Do Mercosul
26
Embrapa Agroindústria Tropical, Fortaleza/CE - Fevereiro/2001
27
Apigenina:
almeirão, salsa, aipo, maçã

Resveratrol:
uvas roxas, amendoim, vinho, mirtilo

Kaempferol:
boldo, chá verde, chá preto, chá mate
SUCOS DE FRUTAS
COM HORTALIÇAS

30
SUCOS DE FRUTAS E HORTALIÇAS

- AUMENTO DAS CONCENTRAÇÕES SÉRICAS DE ANTIOXIDANTES

- AUMENTO DA CONCENTRAÇÃO SÉRICA DE FOLATO, Ca, Mg e K

- REDUÇÃO DOS NÍVEIS SÉRICOS DE HOMOCISTEÍNA

- REDUÇÃO DE MARCADORES DE OXIDAÇÃO DE PTN, LIPÍDEOS E DNA

- MELHORA DE MARCADORES DE INFLAMAÇÃO E FUNÇÃO ENDOTELIAL

J Am Coll Nutr 2011 Oct;30(5):285-94


Asia Pac J Clin Nutr 2007;16(3):411-21
31
J Nutr 2003 Jul;133(7):2188-93
ACCEPTED MANUSCRIPT

I nteractions Between Phytochemicals From Fruits And Vegetables: Effects On Bioactivities

And Bioavailability

M inh Anh Thu Phan1, Janet Paterson1, M artin Bucknall2 and Jayashree Arcot1,*
1
Food Science and Technology, School
ACCEPTED of Chemical Engineering, UNSW Australia, Sydney
MANUSCRIPT
2052 EFEITOS ESPERADOS:
2
M ark Wainwright Analytical Centre, UNSW Australia, Sydney 2052
IC50 (B)
* Corresponding author
10 (email): j.arcot@unsw.edu.au
Concentration of compound B (mM )

Abstract a

Antagonism
The combinations of two or more phytochemicals bring about changes in the ultimate biological
b
effects and/or the bioavailability
c of each component. A number of mixtures of pure bioactive
5 Synergy

compounds or phytochemical-containing plant extracts provide synergy with regard to


d

antioxidant status, anti-inflammation, anti-cancer and chemoprevention of several oxidative


50 IC (A)
stress and metabolic disorders in vitro. The biological activities of food phytochemicals depend
0
0 5 10 15
upon their bioaccessibility and bioavailability which can be affected by the presence of other
Concentration of compound A (mM )

food components including other bioactive constituents. The interactions between


Figure 1. Isobologram of binary mixture at 50% activity (IC50): Addition: a line formed from
- 21% das misturas apresentavam sinergismo
phytochemicals during intestinal absorption could result in changes in the bioavailability of the
IC50 of compound A and IC50 of compound B: any combination points fall in this line indicate
- 54% adição
compounds, which in turn
additive affects the lower
intensity of their bioactivities. This paper provides anthis
- effect;
25% Synergy:
antagonismo left area of addition line: any combination points that fall in

area (e.g., points c and d: form a concave curve) indicate synergistic effect; Antagonism: upper
Interações entre Fitoquímicos de Frutas e Vegetais:
Bioatividade e Biodisponibilidade

INTERAÇÕES BOAS:
- Antocianinas + catequinas

- Mistura de carotenóides é melhor que carotenóide isolado: licopeno + B-caroteno,


licopeno + luteína, B-caroteno + luteína, licopeno +astaxantina

- Lipofílico + hidrofílico: carotenóides + flavonóides (quercetina, rutina),


carotenóides + ácido fenólicos, carotenóides/vitE + vitaminas hidrossolúveis, vitE +
quercetina, ac ferúlico e ac cafeico

INTERAÇÕES RUINS:
- Vit E + ácido clorogênico
- B-caroteno + polifenóis do chá verde
activities

Extract combinations Antioxidant assay used Synergistic rate* References

(1:1, v/v ratio) (%)

Tomato + onion ABTS 32 Gawlik-Dziki

Xanthine oxidase 11 (2012)

inhibitory

Tomato + Garlic ABTS 50

Xanthine oxidase 35

inhibitory

Tomato + Lettuce ABTS 5

Xanthine oxidase 15

inhibitory

Lipoxygenase inhibitory 23

Tomato + Garlic + Lettuce ABTS 30

Xanthine oxidase 22

inhibitory

Lettuce + Green tea Liposome oxidation 16a Altunkaya et al.

Lettuce + Grape seed extract Liposome oxidation 17a (2016)

Eggplant – Purple potato DPPH 46.6 Jiang et al. (2015)


ABTS 47.9

Carrot – Purple potato DPPH 73.4

ABTS 82.1

Carrot – Eggplant DPPH 87.4

ABTS 81.8

Tomato – Purple potato DPPH 35.5

ABTS 45.5

Tomato – Eggplant DPPH 71.4

ABTS 80.6

Tomato + Purple cauliflower ORAC 20.3 Wang et al.

Soybean + Adzuki bean ORAC 14 (2011)

Apple + Purple cauliflower DPPH 15

Raspberry + Mushroom ORAC 12.2

Apple + Tomato ORAC 7.5

Raspberry + Adzuki bean FRAP 19.5

DPPH 31.5

ORAC 8.2

Raspberry + Soybean ORAC 10.1

DDPH: 2,2-Diphenyl-1-picrylhydrazyl assay; FRAP: ferric ion reducing antioxidant power;


purpose in this review.
a
Reported value of synergy at pH 6

Extract combinations (1:1 Antioxidant assay used Synergistic rate* References

ratio) (%)

Apple + Black bean FRAP 7.6 Wang et al.

Raspberry + Black bean ORAC 14.1 (2011)

Apple + Adzuki bean ORAC 9.3

Apple + Black bean ORAC 8.5

Tomato + Soybean DPPH 5.2

Broccoli + Adzuki bean ORAC 13.7

Tomato + Adzuki bean ORAC 8.3

Purple cauliflower + soybean ORAC 7.2

Purple cauliflower + Black ORAC 8.4

bean

Sumac + Raspberry ORAC 10 Wang et al.

FRAP 15 (2015)

DPPH 45

DDPH: 2,2-Diphenyl-1-picrylhydrazyl assay; FRAP: ferric ion reducing antioxidant power;

ORAC: Oxygen radical absorbance capacity; ABTS/Trolox equivalence antioxidant capacity


Kefir x Inflamação
Estudo modelo experimental - ratos

Nutrition, Nov 2016 – DOI: 10.1016/j.nut.2016.11.001


Glicosinolatos sulfurofanos

CRUCÍFERAS NA DCV
Sulfurofanos (isotiocianato)

38
Atherosclerosis 225 (2012) 29-33
CRUCÍFERAS NA DCV

Efeito do sulforafano pode ser obtido via dieta!

Níveis sérico de 80nM reduzem lesão na camada íntima vascular!

300g de vegetais enxofrados!

39
Atherosclerosis 225 (2012) 29-33
Biodisponibilidade Sulfurofanos
Glicosinolatos + enzima mirosinase = isotiocianatos

- Mastigação e processamento do vegetal

- Cofatores enzimáticos

- Tratamento térmico

- Quantidade de água usada

- Acidez gástrica

- Fermentação colônica

Proceedings of the Nutrition Society (2007), 66, 69–81


Óleo Semente de Uva
Compostos Hidrofílicos:
- Catequinas, epicatequinas, trans-resveratrol,
procianidina
- Taninos
- Ácido gálico

Compostos Lipofílicos:
- Tocoferóis
- Fitosteróis
BMI (kg/m2) 32.62 4.77 31.09 4.72 5 0.001 32
WCa (cm) 114.92 9.64 107.38 2.91 0.002 109
HC (cm) 122.48 7.63 117.30 8.27 5 0.001 120
WHRa http://informahealthcare.com/ijf
0.93 ISSN: 0.05 0.91
0963-7486 (print), 1465-3478 (electronic) 0.09 0.197 0
WHtR 0.722013 Informa
!
0.07
Int J Food Sci Nutr, 2013; 64(6): 706–710 0.49
UK Ltd. DOI: 10.3109/09637486.2013.775228
0.06 5 0.001 0

¼ bodyARTICLE
BMIRESEARCH mass index, WC ¼ waist circumference, HC ¼ hip circumference, WHR ¼
* Paired t-test.
For personal use only.

a
UseDoes grape seed oil improve inflammation and insulin resistance in
non-parametric test.
overweight or obese women?*
Pardis Irandoost 1, Mehrangiz Ebrahimi-Mameghani 2,3, and Saeed Pirouzpanah 4
TableStudent
4. Research
1
Comparison of changes in biochemical parameters.
2 3 4
Committee, Nutrition Research Center, Department of Nutrition, and Department of Nutrition in Community, School of
Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
od Sci Nutr Downloaded from informahealthcare.com by Queen's University on 08/10/13

Abstract GSO (n = 20) Mean


Keywords SD
Grape seed oil (GSO) is reported to improve oxidative stress and lipid profile. However, the Females, grape seed oil, inflammation, insulin
ameliorating effect of GSO on inflammation and insulin resistance has not being noticed so far. resistance, obesity
Variable Before
We aimed to examine the effects of GSO consumption on inflammation and insulin resistance After p*
in overweight or obese females. The subjects (n ¼ 44) were randomly assigned into intervention History
group as ‘‘GSO’’ (consuming 15% of energy from GSO) and control group as sunflower oil ‘‘SFO’’
a
FBS (mg/dl) 95.15 9.71 90.50 7.902013
Received 29 October 2012
(consuming 15% of energy from SFO) through a weight loss diet for 8 weeks. Anthropometric
Revised 19 January
measurements, dietary recall and fasting serum glucose, insulin, high sensitive C-reactive
0.001
a(hs-CRP) and tumor necrosis factor-alpha (TNF-a) were assessed before and after the
Accepted 30 January 2013
Insulin (mIU/ml)
protein
15.40 5.54 13.42 5.06
Published online
intervention. Homeostatic model assessment of insulin resistance (HOMA-IR) scores, hs-CRP and 18 March 2013 0.005
a in the GSO group. The hs-CRP was lower in GSO than the SFO group (p5 0.03).
HOMA-IR TNF-a decreased
3.68 1.50 3.05 1.32 0.001
For personal use only.

GSO consumption seems to improve inflammatory condition and insulin resistance in


a,b
hs-CRP (mg/l)
overweight/obese women.
6.04 2.93 3.24 1.79 5 0.001
a
TNF-a (pg/ml)
Introduction
13.35 1.222009; Fiori, 2007)12.58 1.30 0.02
and improve lipid profile (Asadi et al., 2010;
Chung et al., 2003; Kim et al., 2010; Maheswari & Rao, 2005).
Obesity is a public health concern in worldwide and well-
FBS¼ fasting blood sugar, HOMA-IR ¼ homeostatic model assessment of insu
GSO consists of several bioactive constituents, such as free fatty
established to be in association with inflammation (Abbasi et al.,
acids, vitamin E (tocopherols and tocotrienols) and low amount of
2002; Shoelson et al., 2007; Thompson et al., 2011). It is well-
TNF-a ¼ tumor necrosis factor-alpha.
known that several obesity-related chronic disorders are
etiologically attributed to imbalanced inf lammatory factors such
polyphenols (Fiori, 2007; Freitas et al., 2008; Maier et al., 2009).
Fatty acid composition of GSO is similar to sunf lower oil (SFO).
GSO contains large amount of unsaturated fatty acids, linoleic
* Paired t-test.
as high-sensitive C-reactive protein (hs-CRP), tumor necrosis
factor-a (TNF-a) and interleukins (IL), i.e. IL-6 and IL-1b
acid (60%–75%) and oleic acid (14%–22%) (Matthäus, 2008).
a
Use non-parametric test.
(Shoelson et al., 2007; Yudkin et al., 1999). These cytokines have
There are high amounts of tocopherols and tocotrienols in GSO
(Freitas et al., 2008), which the latter is rare in other commonly
b been revealed to play important role in the development of insulin

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