Peter Surai, PhD, DSc Feed-Food. Ltd., Scotland, UK Szent Istvan University, Godollo, Hungary Trakia University, Stara Zagora, Bulgaria
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1 Nutritional modulation of the antioxidant system of the body Peter Surai, PhD, DSc Feed-Food. Ltd., Scotland, UK Szent Istvan University, Godollo, Hungary Trakia University, Stara Zagora, Bulgaria
2 Free radicals and toxic products of their metabolism Antioxidant protection
3 How many free radicals are produced each day? About O 2 molecules processed by each rat cell daily and the leakage of partially reduced oxygen molecules is about 2%, yielding about 2 x10 10 molecules of ROS per cell per day (Chance B., Sies H. and Boveries A., 1979) Prof. Bruce Ames has shown that the DNA in each rat cell is hit by about 100,000 free radicals a day.
4 The major cellular target for free radicals Target Damage Consequence DNA Protein PUFA Scission on deoxyribose ring; base damage; strand breaks; cross-linking Aggregation and cross-linking; fragmentation and breakdown; modification of thyol groups Loss of unsaturation; formation of reactive metabolites (e.g. MDA) Mutations; translational errors; inhibition of protein synthesis Modified ion transport; increased Ca influx; modified enzyme activity Altered membrane fluidity, permeability and activity membrane-bound enzymes
5 Free radicals Three major levels of the antioxidant defence in the cell Free radicals SOD Glutathione First level of defence Second level of defence Third level of defence Lipases, proteases, etc. Uric acid Vitamins A, E, C, carotenoids, Se-GSH-Px Se-GSH-Px Free radicals Catalase Metal-binding proteins Free radical
6 Antioxidant-prooxidant balance in the cell Diet optimization Stress conditions antioxidants prooxidants Antioxidant protection and maintenance of good health Lipid peroxidation and protein oxidation and development of different diseases
7 Antioxidant team All antioxidants in the body are working together as a team (antioxidant system), responsible for prevention of damaging effects of free radicals and toxic products of their metabolism
8 Nutritional modulation of the antioxidant system Modulation of the antioxidant system of the developing chicken embryo by maternal nutrition can be used as a model system
9 Maternal effect of antioxidants Antioxidants in the diet: vitamin E, carotenoids, ascorbic acid, selenium, flavonoids Laying hen Egg yolk: tocopherols, tocotrienols, Carotenoids, Se Embryo: tocopherols, tocotrienols, carotenoids, ascorbic acid, glutathione, uric acid, coenzyme Q, GSH-Px, SOD Developing chicken: growth, immunity, disease resistance
10 Fatty acid composition of egg yolk and liver of newly hatched chick, % Fatty acid Egg Liver 16: : :1n :1n :2n :4n :6n Total PUFA Surai et al., 1999
11 Major feed-derived antioxidants Vitamin E Carotenoids Selenium Vitamin C Flavonoids Essential oils Other minerals ( Mn, Zn, Cu, Fe)
12 Vitamin E Transfer From Feed to Egg Yolk alpha-tocopherol, ug/g Days of experimental feeding Surai, 2002
13 Relationship Between Vitamin E in the Egg Yolk and Liver Vit. E in the liver of day old chick, ug/g Vitamin E in the egg yolk, ug/g Surai, 2002
14 Effect of vitamin E in laying hen diet on lipid peroxidation in chick embryo tissues 120 MDA, ug/g/hour Liver YSM Brain Breast muscles Leg muscles Kidney Heart Surai et al., 2000
15 Some target genes regulated at transcriptional level by vitamin E Gene Class Function Effect of vitamin E Inflammatory cytokines Inflammation Inhibition Apoptosis Induction of apoptosis Inhibition Regulation of Induction of inflammatory genes Inhibition transcription Regulation of Induction of immune response Induction transcription Antioxidant defence GSH biosynthesis Induction Detoxification Detoxification of endogenous and Induction exogenous compounds Lipid metabolism Lipid uptake, delivery transport Inhibition Mocchegiani et al., 2014
16 Carotenoids Carotenes Xanthophylls -carotene -carotene -cryptoxanthin Lutein Zeaxanthin Lycopene
17 Canthaxanthin in egg yolk Surai et al.,
18 Canthaxanthin in the liver of day old chick W 35-W 55-W Surai et al., 2003
19 Effect of canthaxanthin on lipid peroxidation in the liver of newly hatched chicks W 35-W 55-W Surai et al., 2003
20 Effect of canthaxanthin in the breeder s diet on the AO system of the day-old chicken, % 59 Zhang et al., 2011
21 Alterations in gene expression in mouse liver after treatment with lutein Positive regulation + fold change Negative regulation -fold change GSH-Px Glutathione 2.27 reductase Peroxiredoxin TR SOD TR Uncoupling protein 3.53 SOD (mitochondria) Nucleoredoxin 2.94 Isocitrate 3.31 dehydrogenase Copper chaperon for SOD 5.02 NADPH-oxidase 1.63 Sarpeloni et al., 2014
22 15 P As Sb S Se Te Cl Br I
23 GSH-Px (5 forms) Selenoprotein P Selenoprotein W Methionine sulfoxide reductase B Thioredoxin reductases (3 forms) Iodothyronine 5 -deiodinases (3 forms) PH-GSH-Px Antioxidant defence Redox regulation of gene expression Thyroid metabolism Sperm structure integrity Diseases: Muscular dystrophy Exudative diathesis Pancreatic atrophy Encephalomalacia Impaired fertility Decreased:egg production, hatchability, chick viability, growth, immunocompetence, meat quality, feed efficiency Poor feathering Increased cold sensitivity Sperm motility, viability and fertilizing capacity
24 Effect of Se in maternal diet on GSH-Px activity in the progeny chicken liver, U/g 1,6 1,4 1,2 1 0,8 0,6 0,4 0,2 0 Control Se Day 1 Day 7 Day 14 Day 21 Day 28 Pappas et al., 2005
25 Effects of different sources of selenium (0.15 ppm) on TrxR1 activity of liver and kidney in broiler breeders (A) and their offspring (B). Lingnan Yellow broiler breeders, SS-sodium selenite, SM- selenomethionine, SeY- Se-Yeast (Yuan et al., 2012)
26 Effect of dietary Se (0.3 ppm) in maternal diet on AO enzymes in muscles of newly-hatched chicks, U/mg protein (Wang et al., 2011)
27
28 Transcriptional changes in the oviduct in Cobb breeders Pathway/function Sodium selenite Se- Yeast Selenoproteins Protein synthesis Translation of RNA Protein synthesis and metabolism Protein synthesis and metabolism Oxidative phosphorylation Ubiquinone Down Up Ubiquinone biosynthesis Se concentration in oviduct was 0.086; and mg/kg respectively (Brennan et al., 2011)
29 The mother diet influenced expression of at least 11 gens in the intestine in the offspring at day 3 and day 14 Genes that are higher expressed at day 3 and day 14 of age in the chicks of which the mothers received the higher mix are involved in epithelial turnover/ proliferation and maturation of intestinal cells
30 Selenium is an effective regulator of antioxidant system via participation in the synthesis of various selenoproteins Effects of Se on gene expression and maintenance of the redox status of the cell need further investigation Se efficacy depends on the form of the element in the diet with organic Se (SeMet) being more effective than traditional sodium selenite
31 FLAVONOIDS FLAVONOLS FLAVONES PROANTOCIANIDINS quercetin kampferol rutin myricetin galangin ISOFLAVONOIDS isoflavones apigenin luteolin quercetagetin chrysin coumestans FLAVANONES Flavan-3-ols i.e. catechins genistein diadzein formononetin biochanin A coumestrol myricetin naringin naringenin hesperetin (-)-epicatechin (-)-epigallocatechin (+)-catechin 55
32 56
33 Antioxidant system Vitamin E and CoQ Head-quarter CAROTENOIDS: Communicating services > 600 compounds Mynistry of Defence Gene expression and synthesis of AO enzymes and other antioxidants Flavonoids: POLiCE > 8000 compounds Vitamin C: Special forces: 2 compounds Selenium Chief-executive
34 Antioxidant system maturation in piglets (adapted from Yin et al., 2013)
35 Antioxidant system in early (14d) weaned piglets (adapted from Yin et al., 2014)
36 Stress and Adaptation GSH Stress AO-Defences Vit.E-recycling AO reserves, Co-factors Vitagenes AO-enzymes (SOD, GSH-Px, et al.), Chaperones (HSP), sirtuins, etc. apoptosis Immunosupression, decreased reproduction, problems with growth and development
37 Thank you very much for your attention
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