Thank You chairman good afternoon ladies and gentlemen it's a great pleasure to come here and I would like to thank organizing committee for giving me this opportunity to talk about notational modulation of Santee oaks and capacities in poetry and I would like to start from this slide actually for you to understand that we are living in this dangerous world of very radicals and professor birch already address the question that yes free radicals are produced in biological systems and we need to remember that they are produced in physiological conditions and we are talking about at least 20 billions of free radicals which are produced in every cell every day in physiological conditions and in stress conditions this production goes up and therefore we need this kind of umbrella we means chicken speaks humans everybody needs a protection and this umbrella we called antioxidant protection an antioxidant protection is built from antioxidants which are coming from the feed ingredients and feed supplements and yes those free radicals which are produced in nature what are they we simply we can call them activated molecules of oxygen why activated oxygen is very important for the metabolism but once the molecule of oxygen is activated is becoming very very reactive and in can damage lipids including membranes proteins and DNA and the damaging effect of those free radicals is very important and what we need to remember that there is a plenty of different antioxidants in the body and all those antioxidants have working as a team so this is a team work and in this team every member of the team has its own job to do this is my book from 2002 where we described this team first therefore if you look at this team on toxin system I called vitamin E headquarter and yokes and defense carotenoids more than 750 roles in nature communicating services of antioxidant defense flavonoids anti-oxidant police vitamin-c special forces of antiox and defense and finally selenium chief executive on torques and defense and hopefully at the end of my presentation you will understand why I put selenium so high in here our key of all antioxidants and finally there is a Ministry of Defense inside of the cell which means the gene expression transcription factors which are responsible for synthesis their own antioxidants and what we need also to remember that there is a very delicate balance between antioxidants and Pro oxidants in every cell and in body itself and depending which part of the balances goes down we are talking about antioxidant protection and maintenance of good health I'll tell ultimately if right side of the balances goes down due to high level of Pro oxidant stress conditions or just low antioxidant potential that we'll be talking about lipid peroxidation protein oxidation and development of different diseases in fact from Medical Sciences we know today that most of human diseases at various stages of their development are associated with overproduction of free radicals and now come back to poetry if we look at the poultry production we have plenty of different stresses during a poultry production system and these stresses can be divided in four different categories including nutritional stresses and there are mental stresses technological stresses internal stresses and our commercial poultry production design in such a way that it's practically impossible to avoid those stresses and what we need also to know that at the molecular level practically all stresses are related to all the production of free radicals it doesn't matter which stress we are talking about that nutritional stress as there are mental stress or internal stress if we look at the level of mitochondria if we the level of the cell we will see the over production of free radicals and impose oxidative stress okay we have field we have plenty of different compounds on field which actually possess antioxidant activity including vitamin E carotenoids selenium carnitine tower in vitamin C flavonoid synthetic antioxidants which we can continue this release we know that for example this free first three should come from the field because they are not produced in the body but carnitine Towelie in vitamin c can be synthesized however in stress conditions the synthesis of these antioxidants can be compromised and therefore in many cases in stress conditions supplementation Zeb with diet could have a positive response and today we will be talking about nutritional modulation of the antioxidant system and I look at the literature and decided to choose they're actually improving development of the chicken as a model to show how antioxidant system can be modulated so nutrition and this system is very sensitive because if you look at the fatty acid profile of the chicken egg we are talking about at least eighteen percent of polyunsaturated fatty acids which are very sensitive to oxidation but during embryonic development this percentage of polyunsaturated fatty acid increased dramatically so almost 50 percent of lipids in new in the liver newly hatched chick are unsaturated therefore they are very sensitive to oxidation and the protection of against oxidation by antioxidants is a key and we have been developing this idea for many years that Hajin process itself is an oxidative stress so this paper were published in 1996 this one twenty years later and the issue still there it's proven today yes during hatching process when you have high temperature high humidity the oxidative stress has taken place and Prevention of oxidative stress at the time of Hutchins could be a way to improve our ability to improve chicken viability post Hajj including the God development and immune system development so when we look at the this model of modulation of antioxidant system we have antioxidants in the diet then we have brittle in hand which actually consumes his diet in this and toxin come into her and then they are transferred to egg yolk and some to egg white and during embryonic development embryo is able to synthesize their own and toxins like antiox and enzymes and finally they build this antioxidant system which is responsible for maintaining gross immunity for maintaining girls and the rich start from vitamin E vitamin E my favorite one because my first publication of vitamin E was in 1981 and the last ones this year so my line working with with a mini all the life and we know today is that vitamin E is imagined to extent in biological membranes there is plenty of vitamin E in different feed ingredients but the major source of vitamin E of course is the Paramus and this study what we showed here that when during embryonic development with a mini accumulation in the liver up to the point of Hutchins is considered as adaptive mechanisms they adopt a mechanism to deal with that stress of hutchins and it's true for chicken turkey duck gives all the same the highest level at hydrogen but after hajj for the first two weeks the concentration of vitamin E decreased with more than 22 arts that's exactly the place where oxidative stress is taking place how can be modulated yeah if we include high level of vitamin E in the layer diet we can increase vitamin E concentration dramatically more than ten times what's also important when we excluded with a mini from the diet for after a few days with a mini dropped very quickly which means there is no vitamin E reserves in layers body and we also found there relationship between vitamin e in say egg yolk and vitamin e in the liver of newly hatched chick which means with a mini quite effectively transferred from the egg yolk into embryonic tissue during embryonic development and finally finally we proved the point when we use high levels of vitamin E supplementation we increase recommended concentration ins egg yolk in embryonic tissues and in the tissues of day-old chicks you can see lipid peroxidation decreased practically in all tissues therefore the conclusion is yes by inclusion in the diet high level of vitamin E we can modulate antioxidant system the second one is a group of compounds called carotenoids which as I mentioned more than 750 compounds and nature's a divided into carotenes and xanthophylls and for us most important c-spot Santo fields and we did a research showing that by inclusion of the contacts until in the contacts until one of those carotenoids which most easily most effectively transfer from the feet to the egg we actually can substantially increase concentration of contacts and teen in the in the egg yolk and that's a picture so by using contacts and teen you can go from here low to red what is also important look here there is a direct relationship between zocalo of egg yolk and shank on those cheeks and this is two weeks post hearts used to see effect on maternal diet on carotenoids in those cheeks when we look further contacts on teen in the level they were cheeks the same picture which means contacts Santini's effectively transferred from the egg into the embryonic tissue and tissues of post hot chickens and finally by increasing the level of contacts on teen we can decrease decrease lipid oxidation which means that by using contacts and it we can moodily an anti ocean system and can improve resistance or tissues to oxidative stress and also important this paper came from China showing that by using contacts on Tinian Zee diet we can also increase activity of super oxy decent so galaxy dismutase is nothing to do with content accent in this means and there is a interactions between different antioxidants in biological systems we published cutaway views showing how contacts sentian can be used in poetry industry but looking at nature situation you can see this dramatic difference between house and feral birds and ducks and geese and if we look at the wild nature carotenoids playing very important signaling function and finally finally we come into my favorite one - selenium and today we are talking about celebrating 200 years of selenium discovery by swedish chemist chemist bill Salus and today we know that selenium is a part of arranged celina proteins which are playing important role in many physiological functions in this paper paper review we try to actually combine or divide cellular proteins in different groups those which participate in an talks and defense those which are responsive paradox regulation of gene expression those which are involved in thyroid metabolism and maintain sperm structure and integrity and what is known today is that up to 50% popped up more than half of all those sarena protein known we know today 25 cellular proteins in poultry are involved directly or indirectly into antioxidant defenses and I have been developing for many years organic selenium concept because what we saw which was shown in our research that the form of selenium sometimes more important since the concentration of selenium and the assimilation of selenium from the diet is a very important issue and organic selenium means we look would the form of selenium and feed ingredients so any fit ingredients we take my ears soya a wheat in all those feed ingredients selenium is in organic form mainly as a Selina massage but we are supplemented birds by premises still using sodium selenite and these two forms are very different so this my Selina book which is 974 pages and it took me almost thousand pages to prove the point that organic selenium is a major form of selenium and the most effective form of selenium then it was another book 2008 this is a chapter last year and this is a new book which is coming and the message is the same the form of selenium is a key for success and let's look at some results this paper we published in British 40 science from the trial we're on at the Scottish Agricultural College so what we use semi-synthetic diet reasonably low in in selenium commercial diet and two different level of organic selenium supplementation what we showed we showed that by using organic selenium in the diet we can substantially increase selenium concentration albumin and selenium concentration in egg yolk and this is a liver liver newly hatched cheek the same relationship the same as you saw with vitamin E the same as you saw as karate noise yes Liam is effectively transferred during embryonic development from the egg and white into tissues of newly hatched cheek as a result of transfers that selenium we saw significant increase in activity of glutathione peroxidase in newly a cheek and in cheek five days post harsh as a result of increase auntie works and defenses you can see decreased susceptibility to oxidation so lipid peroxidation went down therefore in 2003 showed yes by using organic selenium in the diet of the breeders it is possible to improve and to oxidant defenses by increasing expression of various arena protein in our cases it was glutathione peroxidase and this paper actually published 15 years later after our paper what they did here they actually use the diet which was almost the same as ours basal diet 0:04 they supplemented to differ different sources of selling of sodium selenite and Celina methionine at point 15 and once they did here most important parts a thermal stress because when we talking about antioxidant the protections they provided it's extremely important in stress conditions their higher the stress the more importance of nutrition of modulation of antioxidant system the more importance of antioxidant and in this case its we are talking about selenium so the stress was seventeen days of incubation eggs were placed for six hours at certain nine point five degrees what did they show they shows the same as in our paper yes the lipid oxidation oxidation goes down and you can see here different letters but they between sodium selenite and Salina methanol which means it's significantly better effect of organic selenium but more important this one protein oxidation because the protein oxidation that something which we do not pay much attention for many years we know that lipid oxidation is bad we know we have plenty of technique to assess lipid oxidation that's why we were talking exclusively about this one for many years but today we're talking more and more important oxidation and negative consequences of protein oxidation or for immunity for gutturals for many other parameters therefore one more point vitamin E and other classical auntie ocean cannot affect protein oxidation and that's a bad thing but here you can clearly see that using organic selenium it's a poor possibility to improve stability of proteins in stressed conditions again one more paper came from China showing that actually inclusion of organic selenium as a selenium ethylene improves superoxide dismutase activity in muscles of neural energy again showing the sames and there is interactions between different antioxidants in biological systems okay we published recently three reviews which were addressing selenium for breeders selenium for sows and selenium for balls and all those reviews confirming the same idea that organics is more efficiently used by animals by poetry by pigs by boars and the organic selenium can help to improve antioxidant defenses finally I talked to your organic selenium is good but let's look how it works in the board if we understand how it works that it will be easier to explain plain to those results which are already published so become selenium in feed ingredients and there are plenty of different forms of selenium there including selenium as iron in solenoid cysteine Selena glutathione Selena peptides and this list can be continued because at least in yeast it was shows and there are more than 50 different organic compounds then we have selenium supplements today we can supplement diet with various forms of selenium including selenium is iron and zinc selenium Athene and hydroxyl in the methionine Selina he said in a methane insulin I sell innate in other forms of selenium now if the bird consumes his feed all these forms of selenium coming to the God and the gods there is some catalyst is taking place which means ink Selina Matheny will be converted into Selina metha anhidrosis and in Amazon in at least part of it can also be converted in salina miss island but the absorption efficiency is not hundred percent therefore we will lose some selenium olivia education from we are fishes and urine and what is important now important point is that all those forms of selenium from the god coming to the liver because the liver is a major organ for metabolism of selenium and metabolic changes are taking place therefore you can see here solenoid cell innate Sarah not sustained Sarina methionine and answer form of selenium coming to the liver to the metabolism and here important point selenium eaten in organic form of selenium chemically is very similar to methyl and many enzymatic system is body cannot distinguish what is ward there for selenium asylum can be not specifically incorporated into newly synthesized proteins there for selenium Asylum can go to amino acid pool and not specifically incorporated in muscles buildings selenium reserves in the body so this part is the most important to understand that organic selenium in the form of selenium Athenian can go one way to deliver to be metabolized and go to amino acid food to be incorporated into proteins and build selenium reserves okay in the liver all those forms of selenium will be destroyed and converted in the common product hydrogen selenide it does matter saline existing cell in the methane in selenite Rosellini all of them will be converted in this product and then from hydrogen selenide saline at sustain will be synthesized so he important point saline at sustain is a feed and saline at sustains this one are completely different in all these things only you will synthesize saline at sustained can be incorporated in those 25 Selena proteins okay I'm so selling our proteins as I mentioned already are participating in antioxidant defenses so until here the picture more or less clear and the most important part coming here in stress conditions that's what I told you that in stress conditions the importance of an toxin goes up so in stress conditions what's happened the physiological response to stress is a catabolism of proteins so protein catabolism that something which happen in in any stress conditions so during protein catabolism some Selena methionine will be released and converted to the same hydrogen selenide and eventually we will have in increase expression of Selena proteins because we supply more selenium and given the opportunity to Selena proteins to be expressed then we have antioxidant defenses goes up and we have maintained in gross development productive and reproductive performance in stress conditions so that's a major understanding today the building selenium reserves in the body by organic selenium is a form of selenium ethylene is a major mechanism of advantages of organic selenium in poultry production and if we look further now what we need to do we need to choose a right form of selenium because we need to build reserve the highest reserve the bed as a protection in fact building these reserves in the board it's like a insurance policy so in order to have good insurance they know that we have insurance which comprehensive one you need to build selenium reserves and if you if you look at these two publications when actually make a comparison between sodium selenite cell in the yeast and hydroxy cell in a methionine the biggest response the best response was from hydroxyl in a methionine and more recent paper published this year still showing the same set hydroxy Salina methionine in the diet of the Lay's actually in the diet so oil is the same actually built in selenium reserves more efficiently so this is a significant difference in both types of muscles so now what we can conclude from this one we have three generations of selenium supplements the first generation was solid M selenite and serenade which came in nineteen seventies in 1970s we where scientists still did not realize margins there are different forms of selenium so Cellini was considered like a mineral in 1970s there was a big problem of selenium deficiency global problem it was necessary to solve that problem and so you're selling I did a good job solves a problem selenium deficiency but today we are not talking about selenium deficiency in anymore action we are talking about meeting requirement we are talking about precise nutrition and we need those tools to deal with this one therefore the second generation of selling of supplements including cell in the yeast and Pearson in the methane so Selina is did a very good job for many years now myself was promoted Selena methane Selina years and we know today that Serena is good but there isn't one question to answer the active compound of cellular yeast is Selena Messiah and in the history enemy fire comprises only from 50 to 70 percent of total selenium what about as a former say what about selling that sustains and other forms in my scheme I showed you they are no different from sodium selenite it's only selling Amazon which given the value therefore when you are talking about Selena news yes that were your first is from 50 to 70 percent and secondly it's quite variable because the technology of saying the is production is not able to be a to guarantee the exact percentage of Selena methania okay what about pure said in a methylene we can use pure selena methylene yes it's a nice product but there is one no but the stability of the pool because chemical cell in Amazon is not very stable therefore when you're talking about feet treatment especially heat treatment or field you can lose some Selena melanin this means that when you using it you're uncertain what the level of selenium Italian left at the time when feed is consumed therefore the third generation of the Selena supplement hydroxy Selena methionine actually combined advantages of wars advantage of Selena Selena yeast as a stable product and advantages pure Selena methionine is a concentrated product so now a couple of minutes more about us and jokes about selenium you know why I put it into category of chief executive what about flavonoids there's a most fashionable part there are hundreds and hundreds paper claiming that flavonoids and plant extracts and polyphenolics are good and dioxins believenot most recent research including my my research my review papers shows that flavonoids are not antioxidants they are not antioxidant traditional antioxidant like vitamin E in the body because you can have very high concentration of those fallen oils in the diet in the god but very tiny amount in the blood and almost known in target tissues therefore those concentrations of flavonoids which were tested in tubes 1000 times higher than those which we'll have in target tissues but there is still effects of flavonoids I'm not saying that flavonoids nough are not effective I'm saying that the mechanist which was described for them is wrong because flavonoids today unknown to regulate transcription factors like an air f2 and some acid therefore there is a need for more research to understand how flavonoids can affect and talks and system how they make the late antitoxin system and my new point those who try to replace with a many ways those flavonoids they put card before horses it's too early to do so because we still do not understand exactly how they work ascorbic acid yeah it's also important antioxidant it's synthesized in the body but in stress conditions like hits tears supplementation of extras complicated could be beneficial especially when it's supplemented with water carnitine well I consider carnitine today as a new entrant into antioxidant family because it's proven today is this our three recent revenues and carnitine what we prove the point that carnitine is effective in maintaining mitochondria integrity so instead of catching radicals like wait a minute do it they regulate or maintain mitochondria in stairs conditions preventing extra free radical production and therefore say supplementation or carnitine stress condition could be one way another way to improve an talks and defenses Tiger e'en that something surprises because the tongue green is non-essential amino acid yes for cats it's widely used because cats are not synthesized it but most animal synthesized styrene but in stress conditions again especially in aging animals the synthesis of toweling goes down an extra towering supplementation could be beneficial and Tolan actually has a similar effect on mitochondria like carnitine doing and finally and tox dissing at dukes of defense mechanism how I see them today I put here twelve major mechanisms and the first one decrease of localized oxygen concentration so once Cox agent concentration done then of course free radical production is done decreased activity or oxidant enzymes in the cells are plenty of various enzymes which are responsible free radical production and once activity of those enzymes down more less free radicals product reduced chain breaking by scavenging intermediate radicals binding metal ions and metal chelation induction of various transcription factors including an array of two and half Kappa B and some others and additional synthesis of antioxidant enzymes the composition of peroxides by converting them into non radical non toxic products improve efficiency of electron transport chain in mitochondria specially in stress conditions prevent in various damages tomato content prevented excess of free radical production antioxidant recycle mechanism including vitamin E recycling this is what very important because in many cases recycling of vitamin E even more importance and concentration itself apoptosis activation and removal terminal damaged cells and redox signaling and Vita gene activation and this our last three papers published betta genes in poultry production with the genes or genes which are responsible for adaptation to stairs and that's something to have a look more specifically how the regulation of which the genes can help and finally how I see today stairs and adaptation because when we are talking about modulation of antioxidant system the whole the whole idea of modulation is actually common that we can improve adaptability of animals to stress we can improve that ability which means instead conditions we lose less productive and reproductive performance so if we look here we have stairs in stress conditions the concentration of glutathione goes down and this will be the signal to activate with a genes activation of Vita genes will be responsive for additional synthesis of antioxidant enzymes including superoxide dismutase for expression of cellular proteins for expression of heat shock protein citrine's and some other active molecules and then this will give an opportunity to improve antioxidant defenses here you also need to have good vitamin e recycling selenium resource in both in the board some cofactor but generally speaking if you look here this is a self-regulating system this is a system of adaptation to stress until you cross this red line you cross red line because the stress is too high or antioxidant defenses are too low once you cross a red line we are talking about apoptosis it's not reversible anymore we are talking about apoptosis immunosuppression decrease productive and reproductive performance of course transcription factor and air F 2 and F Kappa B are also involved here because the nrf2 is responsible actually for synthesis those antioxidants and the other side NF kappa-b is responsive for inflammation and of pro-inflammatory cytokines so looking in this scheme and looking and trying to address what we talking about about modulation when to oxygen system we have choice we have choice of various antioxidants which are common which can come with the diet we have beta many we have carotenoids we have selenium we have other tools and it's a headache for nutritionists to find an optimal combination which can give the best results thank you very much for attention [Music]