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Molecular mechanisms and new strategies to fight stresses in egg-producing birds

Published: December 16, 2016
By: E. Shatskikh 1, E. Latypova 1, V. Fisinin 2, S. Denev 3, P. Surai 3-5.

/ 1 Department of Nutrition and Breeding of Farm Animals, Ural State Agrarian University, Ekaterinburg, Russia; 2 All Russian Institute of Poultry Husbandry, Sergiev Posad, Russia; 3 Department of Biochemistry, Microbiology and Physics, Faculty of Agriculture, Trakia University, Stara Zagora, Bulgaria; 4 Department of Nutrition, Faculty of Agricultural and Environmental Sciences, SzentIstvan University, Gödöllo, Hungary; 5 Sumy National Agrarian University, Kirov, Sumy, Ukraine.


Commercial egg production is associated with various stresses decreasing productive and reproductive performance of layers. A growing body of evidence indicates that most of stresses in poultry production at the cellular level are associated with oxidative stress due to excess of free radical production or inadequate antioxidant protection. Recently, a concept of the cellular antioxidant defence has been revised with a special attention paid to cell signalling. Indeed, in animals, redox signalling pathways use reactive oxygen species (ROS) to transfer signals from different sources to the nucleus to regulate a number of various functions including growth, differentiation, proliferation and apoptosis. The vitagene concept of fighting stresses emerged as a new direction in a nutritional research. Indeed, by improving the adaptive ability of animals to stress it is possible tosubstantially decrease negative consequences of various stresses in poultry and farm animal production. The analysis of recently published data clearly showed that the anti-stress composition developed on the vitagene concept and supplied with drinking water is an effective means in fighting stresses in poultry production.

Keywords: stress, poultry, vitagenes, chickens

Commercial egg production is associated with various stresses decreasing productive and reproductive performance of layers. It is proven that most of stresses in poultry production (technological: chick placement, vaccinations and transfer to breeder houses; environmental: heat stress, high ammonia, etc.; nutritional: mycotoxins, misbalances of vitamins, minerals, amino acids, etc.; or internal: bacterial and viral challenges) at the cellular level are associated with oxidative stress due to excess of free radical production or inadequate antioxidant protection (Surai, 2002; 2006; Surai and Fisinin, 2012a; 2012b; 2013). Therefore, the antioxidant system of the body is responsible for preventing damages caused by free radicals to various biological molecules including proteins, lipids and DNA. Many of the natural antioxidants are provided with the chicken diet (vitamin E, carotenoids, selenium, etc.), while a range of other antioxidant compounds are synthesised in the body (glutathione, thioredoxins, antioxidant enzymes, etc.) and a delicate balance between antioxidants and pro-oxidants in cells, digestive tract and in the whole body is responsible for maintenance of the redox status of the cell (Surai, 2002), activating various transcription factors and ultimately affects chicken health, their productive and reproductive performances. Therefore, reactive oxygen species (ROS) are no longer viewed as just a toxic by-product of mitochondrial respiration, but are now appreciated for their role in regulating a myriad of cellular signalling pathways (Reczek and Chandel, 2015). In fact, a vita-gene network is shown to be responsible for a regulation of the adaptive ability of animals/human to various stresses (Calabrese et al., 2008; 2010; 2012). Recently a new concept of fighting stresses via antioxidant supplementation via drinking water (Surai and Fisinin, 2012a; 2012b; 2013) was suggested and a product PerforMax (Magic Antistress Mix) developed based on the vitagene concept was successfully tested in broiler production (Velichko et al., 2013; 2014) as well as for improvement of the reproductive performance of egg breeders (Shatskikh and Latypova, 2014).
The aim of this paper is to review the roles of antioxidant-containing anti-stress compositions supplied with drinking water in maintaining productive and reproductive performance of layer breeders.
Stresses in poultry production
From a physiological point of view stress is related to deviation from optimal internal and external conditions. In general, there are three major types of stress in poultry industry: environmental, nutritional and internal stresses (Surai, 2006). Environmental stresses started from the moment when egg is laid, since temperature variation could cause embryo to start developing (high environmental temperature) or die (low temperature or fast temperature changes). It is well known that temperature and other conditions of egg storage between egg laying and its placement into the hatchery negatively affect embryonic development. In fact, hatchability of fertile eggs declines with length of storage and there is an increase in percentages of early and late embryonic mortality with length of storage period (Elibol et al., 2002; Fasenko, 2007) and most likely could affect chickens in later life. Furthermore, additional time in hatchery during hatching is also considered to be a stress causing detrimental changes in antioxidant defences of the chick (Karadas et al., 2011). The negative effect of high temperature on hatching eggs could be very substantial during summer heat stress. Indeed, high environmental temperature is one of the most serious factors adversely affecting the laying performance in poultry. Egg production (De Andrade et al., 1977; Mack et al., 2013 ), egg weight (Mashaly et al., 2004; Sahin et al., 2007; Ebeid et al., 2012; Mack et al., 2013), eggshell thickness (de Andrade et al., 1977; Lin et al., 2004; Franco-Jimenez et al., 2007; Ebeid et al., 2012) eggshell percentage (Ebeid et al., 2012), eggshell density (de Andrade et al., 1977) and eggshell breakage (Lin et al., 2004) were negatively affected by high ambient temperature. Elevated temperatures also increase mortality in both layers (Mashaly et al., 2004) and broilers (Quinteiro-Filho et al., 2010).
Furthermore, the gastrointestinal tract is particularly sensitive to stressors, which can cause a variety of changes, including alteration of the normal, protective microbiota (Burkholder et al., 2008) and decreased integrity of the intestinal epithelium (Quinteiro-Filho et al., 2010). Heat stress alters the jejunal glucose and lipid transport in chickens (Sun et al., 2014). Furthermore, heat stress can inhibit the activity of digestive enzymes and reduce absorption and immune functions of intestinal mucosa (Chen et al., 2014). The calbindin concentration was prominently decreased in ileum, cecum, colon, and eggshell gland under heat stress conditions which could be related to the deterioration of eggshell quality characteristics under heat stress conditions (Ebeid et al., 2012). Broilers subjected to the heat stress were characterised by reduced average daily gain and feed intake; lower viable counts of Lactobacillus and Bifidobacterium and increased viable counts of coliforms and Clostridium in small intestinal contents; shorter jejunal villus height, deeper crypt depth, and lower ratio of villus height to crypt depth (Song et al., 2014).
The next stress period is related to the chick placement and the first 24 hours of the chick's life are the most important (Noy and Uni, 2010). It is believed that a chick should have an access to the feed and water as soon as possible after hatching to stimulate the development of the digestive and immune systems. When chicks are placed in winter while outside temperature is quite low there is always a temptation to decrease ventilation to keep energy usage to the minimum. However, it is very important to provide good quality, warm, fresh air that is rich in oxygen for the recently hatched chicks. Indeed, the chick's trachea is very often irritated from being boxed and shipped in the chick trays, often for many hours. Furthermore, chicks can be exposed to formaldehyde gas and contaminated air during hatch. Excessive amounts of irritants such as carbon dioxide and ammonia can cause depression, dehydration, emaciation as well as various problems with the respiratory system of the chick. It is interesting to note that exposure to stressors early on enhanced the chicks' ability to cope with the same or with different stressors later and that compensatory responses occurred as the result of short-term exposure to stressors (Johnson et al., 1991). The increased lipid peroxidation and reduced activities of antioxidant enzymes in healthy chickens reared under unfavorable microclimatic conditions such as higher air temperature and humidity, higher ammonia concentrations, and lower light intensity were indicative about an induced oxidative stress (Georgieva et al., 2011). It should also be mentioned that poor ventilation is often associated with toxic carbon monoxide accumulation. Toxicity causes irreversible physiological and biochemical changes that cannot be corrected with successive additional ventilation. The next stress is related to vaccinations. Indeed, vaccinations are absolutely necessary to maintain chicken protection against various diseases, but when a vaccine activates the immune system there are always negative consequences for productive parameters, since immunity is quite expensive for the body in terms of usage of nutrients and energy. It is generally assumed by immunologists that providing immunological defences to minimise such risks to the host is costly in terms of necessitating trade-offs with other nutrient-demanding processes such as growth, reproduction, and thermoregulation (Lochmiller and Deerenberg, 2000). It has been shown that lipopolysaccharide injection decreased feed intake and body weight gain (Lai et al., 2011) and reduced ileal protein digestibility (Yang et al., 2011). It is well appreciated that efficacy of vaccination is very much dependent on the immunocompetence of the birds, which could be compromised in stress conditions (Surai, 2002). Furthermore, there is a range of immunosuppressive diseases in poultry, including bursal disease, infectious chicken anemia and Marek's disease (Fussell, 1998; Hoerr, 2010). High stocking densities have been reported to be another stressful condition (Puron et al., 1995) causing decreased performance, increased mortality and prevalence of leg weakness (Sørensen et al., 2000), and affecting the carcass quality (Feddes et al., 2002) of broiler chickens. Transferring chickens to breeder houses is always associated with increased stress and sometimes causing feather picking and cannibalism (Gunnarsson et al., 1999). The biggest stress for layers comes at the peak of egg production. Indeed, major compounds of the egg yolk are synthesised in the liver and it is working to its maximum ability and any stress can cause a drop in egg production which very often is not coming up after the stress is removed. Finally, egg shell quality during the second part of egg laying is considered to be a problem, especially when layer age is past 80 weeks (Safaa et al., 2008). Indeed, most losses are related to the poor shell quality of eggs produced at the end of the production cycle. For example, Grobas et al. (1999) found that the percentage of broken eggs from Brown egg-laying hens on the farm increased from 0.43% at 22 wk to 1.81% at 74 wk of age. Microbial and virus challenges are considered to be the main internal stresses causing detrimental consequences for productive and reproductive parameters of birds. Mycotoxins are considered to be among major feed-related stressors in poultry production (Awad et al., 2013; Dhama et al., 2013; Rawal et al., 2010; Battacone et al., 2010) and they cause oxidative stress and immunosuppression (Surai and Dvorska, 2005; Fisinin and Surai, 2012; 2012a;2012b).
In general, all aforementioned stresses suppress reproductive performance of parent birds including reduced fertility and hatchability. Furthermore, stresses are associated with impaired feed conversion, reduced average daily weight gain and increased mortality in growing birds. The immune system is considered to be the most sensitive to various stresses (Hoerr et al., 2010; Surai, 2006; Surai and Dvorska, 2005; Dohms and Metz, 2001). In fact, stress-related dysfunction of the immune system weakens natural resistance to diseases (Antonissen et al., 2014) and reduces efficacy of vaccinations (Ingrao et al., 2013) leading to significant losses in profits.
Molecular mechanisms of stress and antioxidant defenses
It is generally accepted that increased free radical production is the major molecular mechanism of the negative consequences of various stresses in human life and animal/poultry production (Surai, 2002; 2006). Free radicals are atoms or molecules containing one or more unpaired electrons and they are highly unstable and reactive capable of damaging biologically relevant molecules such as DNA, proteins, lipids or carbohydrates. The animal body is under constant attack from free radicals, formed as a natural consequence of the body's normal metabolic activity and as part of the immune system's strategy for destroying invading microorganisms. Recently collective terms ROS and reactive nitrogen species (RNS) have been introduced including not only the oxygen or nitrogen radicals, but also some non-radical reactive derivatives of oxygen and nitrogen (Surai, 2006).
Reactive oxygen species are constantly produced in vivo in the course of the physiological metabolism in tissues. The most important effect of free radicals on the cellular metabolism is due to their participation in lipid peroxidation reactions. In fact, lipid peroxidation is a chain reaction and potentially large number of cycles of peroxidation could cause substantial damage to cells. In membranes the peroxidazable material is represented by polyunsaturated fatty acids (PUFA). It is generally accepted that PUFA susceptibility to peroxidation is proportional to amount double bounds in the molecules. In fact, docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are among major substrates of the peroxidation in the membrane. It is necessary to underline that the same PUFAs are responsible for maintenance of physiologically important membrane properties including fluidity and permeability. Therefore, as a result of lipid peroxidation within the biological membranes their structure and functions are compromised. Proteins and DNA are also important targets for ROS.
The complex structure of proteins and a variety of oxidizable functional groups of the amino acids make them susceptible to oxidative damage. In fact, the accumulation of oxidized proteins has been implicated in the aging process and in other age-related pathologies (Wani et al., 2014; Zhang et al., 2014). A range of oxidized proteins and amino acids has been characterised in biological systems. In general, the accumulation of oxidized proteins depends on the balance between antioxidants, pro-oxidants and removal/repair mechanisms. Oxidation of proteins leads to the formation of reversible disulfide bridges. More severe protein oxidation causes a formation of chemically modified derivatives e.g. shiff's base (Surai, 2006).
During evolution, living organisms have developed specific antioxidant protective mechanisms to deal with ROS and RNS (Surai, 2002). Therefore, it is only the presence of natural antioxidants in living organisms which enable them to survive in an oxygen-rich environment. The general term “antioxidant system” describes these mechanisms, which are diverse and responsible for the protection of cells from the actions of free radicals. This system includes:
  • Natural fat-soluble antioxidants (vitamins A, E, carotenoids, ubiquinones, etc.);
  • Water-soluble antioxidants (ascorbic acid, uric acid, taurine, carnitine, etc.);
  • Antioxidant enzymes: glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD);
  • Thiol redox system consisting of the glutathione system (glutathione/glutathione reductase/glutaredoxin/glutathione peroxidase and a thioredoxin system (thioredoxin/thioredoxin peroxidase/thioredoxin reductase).
The protective antioxidant compounds are located in organelles, subcellular compartments or the extracellular space enabling maximum cellular protection to occur. The antioxidant system of the body is responsible for prevention of damaging effects of free radicals in stress conditions. Therefore, dietary supplementation of antioxidant compounds is a way to improve efficiency of broiler production in commercial conditions associated with various stresses.
Oxidative stress and transcription factors 
Recently, a concept of the cellular antioxidant defence has been revised with a special attention paid to cell signalling. Indeed, in animals, redox signalling pathways use ROS to transfer signals from different sources to the nucleus to regulate a number of various functions including growth, differentiation, proliferation and apoptosis. Various transcription factors are involved in a regulation of the antioxidant defence system (Ma and He, 2012; Majzunova et al., 2013; Song and Zou, 2014; Kweider et al., 2014). These pathways operate in coordinated manner and several are critically important for animals to cope with oxidative stress insults. They include Keap1/Nrf2, NF-κB, Mapk and AP-1 (Luschak, 2011). Particularly great attention has been paid to a basic leucine zipper transcription factor, Nuclear factor-erythroid-2- (NF-E2-) related factor 2 (Nrf2). The recent information can be summarised as follows:
Based on the existing evidence, Nrf2, is considered to be the master regulator of oxidative stress signalling and growing evidence has demonstrated that the Nrf2 antioxidant response pathway plays an important role in the cellular antioxidant defense by activating a great variety of genes involved in early defence reactions of higher organisms (Ma, 2013; van der Wijst et al., 2014). Indeed, Nrf2, has a significant role in adaptive responses to oxidative stress being responsible for the induction of the expression of various antioxidants to combat oxidative and electrophilic stress. In particular, critical components of the cellular antioxidant defence mechanisms include the ROS scavengers, phase II detoxification enzymes, and other detoxification proteins, which contain antioxidant response elements (AREs) in their promoter regions (Howden, 2013; Buelna-Chontal and Zazueta, 2013; Keum and Choi, 2014). There is considerable experimental evidence suggesting that under normal physiological conditions, Nrf2 is kept in the cytoplasm by Kelch-like-ECH-associated cytoskeletal protein 1 (Keap1) and the ubiquitin scaffold protein Cullin 3 targeting Nrf2 for ubiquitylation and subsequent degradation. Indeed, Cullin 3 ubiquitinates its substrate, Nrf2. Furthermore, Keap1 serves as a substrate adaptor, which facilitates the ubiquitination of Nrf2 by Cullin 3 with the following proteasomal degradation resulting in a short (about 20 min) half-life of Nrf2 under normal conditions. Emerging evidence has revealed that Keap-1 acts as a redox sensor and upon exposure to oxidative stress, critical cysteine thiols of Keap1 are modified resulting in Nrf2 to be released from Keap1 and translocate to nucleus. In the nucleus, Nrf2 combines with a small musculoaponeurotic fibrosarcoma protein called Maf to form a heterodimer, and, by binding to the ARE in the upstream promoter region, it initiates the transcription of a number of antioxidative genes, leading to the expression of antioxidant proteins, thiol molecules and their generating enzymes, detoxifying enzymes, and stress response proteins. This includes enzymes of the first line of the antioxidant defence, namely superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) , as well as heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase (quinone 1) (NQO1), glutathione-S-transferase (GST), g-glutamylcysteine synthase (g-GCS) and others contributing to counteracting oxidative damages (Zhou et al., 2014). It is believed that, Nrf2 is controlled through a complex transcriptional/epigenetic and post-translational network that ensures its activity increases during redox perturbation, inflammation, growth factor stimulation and nutrient/energy fluxes, thereby enabling the factor to orchestrate adaptive responses to diverse forms of stress (Hayes and Dinkova-Kosova, 2014). Beyond activation of synthesis of antioxidant enzymes, Nrf2 also contributes to adaptation by up-regulating the repair and degradation of damaged macromolecules, and by modulating intermediary metabolism conducting direct metabolic repro-gramming during stress (Luschak, 2011). Furthermore, Nrf2 may serve as a major regulator of several cellular defence associated pathways by which various cells combat oxidative stress. Moreover, Nrf2 contributes to cellular proteostasis by regulating the expression of molecular chaperones, as well as of additional players of proteome stability and maintenance, namely the proteasome subunits (Niforou et al., 2014). Through inducing the expression of this battery of genes, Nrf2 can augment a wide range of cell defence mechanisms, thereby enhancing the overall capacity of cells to detoxify potentially harmful substances and adapting to various stress conditions. As such, the Nrf2-Keap1 pathway is generally considered to be a major cellular defence pathway (Zhou et al., 2014). It has been suggested that low intensity oxidative stress is mainly sensed by Keap1/Nrf2 system which downstream up-regulates the genes encoding antioxidant enzymes. Intermediate oxidative stress also increases the activity of antioxidant enzymes, but mainly via NF-kB and AP-1 pathways. At both, low and intermediate intensity oxidative stresses, MAP-kinases and other kinases seem to be also involved in signal sensing and cellular response, leading to enhanced antioxidant potential (Luschak, 2011).
Vitagenes and a new concept of fighting stresses 
Recently a new concept of how vitagenes regulate the adaptive ability of humans and animals to various stresses has been developed (Calabrese et al., 2008; 2010; 2012). This concept postulates that there is a range of genes responsible for the synthesis of various antioxidant compounds (heat shock proteins, antioxidant enzymes, sirtuins, etc.) and that there are nutrients, which can affect expression of such genes. Carnitine, betaine, and some other elements are proven to be effective regulators of vitagenes.
Based on the aforementioned positive effects of dietary antioxidants on protection against various stresses in poultry production, a range of anti-stress compositions/premixes has been developed. However, in stress conditions feed consumption is substantially decreased so the effects of feed supplements are also decreased. The new concept was based on an idea that supplying birds with various antioxidants via the drinking water could help them deal with stress conditions more effectively. Indeed, it was proven that inclusion of vitagene-regulating compounds (carnitine, betaine, vitamin E, etc.) in water, as well as some minerals, vitamins, electrolytes and organic acids could be effective in fighting various stresses (Fisinin and Surai, 2011; Surai and Fisinin, 2012a; 2012b; 2013; Fotina et al., 2013). This helps at chick placement, when the antioxidant system is crucial for the digestive and immune system development (Fisinin and Surai, 2012a). In particular, it was proven that inclusion of an anti-stress composition (Antistress Magic Mix, PerforMax) into the drinking water at the University trial improved chicken growth and feed conversion ratio (FCR, Fotina et al., 2011; Fotina et al., 2014). Using the same anti-stress composition in commercial conditions improved FCR during a 39-day broiler growth trial. At the end of the trial, the improvement in FCR due to the anti-stress composition during the first three days post-hatch as well as before and after vaccination was highly significant (Velichko et al., 2013; 2014). In addition, it was shown that the anti-stress composition had an immune-modulating effect in broilers (Fotina et al., 2011), growing ducklings (Surai et al., 2012) and could be successfully used to prevent immunosuppression (Fisinin and Surai, 2013a; 2013b). Improvement of the antioxidant system via supplying the antioxidant composition via the drinking water could help deal with various mycotoxins in feed, including DON (Fisinin and Surai, 2011b; 2011c), ochratoxin A (Fisinin and Surai, 2012d;2012e) and T-2 toxin (Fisinin and Surai, 2021f; 2012g). Furthermore, such a technology could help fight heat stress (Surai and Fotina, 2013).
Effect of the anti-stress composition on layer breeders
The importance and efficacy of using the anti-stress composition (PerforMax, Magic Antistress Mix) for rearing birds and adult egg-type parent stock (Hy-Line) at one of the biggest egg producing farms in Russia (Borovskaya poultry farm, Tumen region) have been described recently and below there is a summary of major findings. The study was conducted with rearing birds as well as with adult laying hens and cockerels of the parent stock (Hy Line Brown, line SD). There were two poultry trials, two physiological trials and a big commercial trial. In total 53400 birds were used (Latypova, 2014).
In the first phase of the experiment, the effect of Magic Antistress Mix (PerforMax) on the rearing birds was studied. There were a control and an experimental group with 2000 females and 400 males in each group. The control group was fed in accordance with Hy Line recommendations with the diet formulated to meet all requirements in major nutrients and energy. The experimental group had an additional antistress supply via drinking water at the level of 100 g per 100 L of drinking water during days 1–5, 9–13, 21–25, 27–31, 45–49, 63–67 and 75–79 which were related to stresses imposed by vaccinations, grading, and transfer to the breeding houses. The experiment lasted for 105 days (Shackih and Latypova, 2014).
In general, growth and development of chickens were similar in both groups with slight increase in body weight (1242 g vs 1200 g) at 15 weeks of age in the experimental female birds. Therefore, the experimental birds were closer to target body weight (1230 g) than control birds. The usage of antistress composition positively affected testes development of 15-week old cockerels (2.47 g vs 1.05 g, P<0.05) (Shackih and Latypova, 2014a). It is interesting to note that in the experimental cockerels testes weight was also improved at 26 and 56 weeks of age (Shatskikh and Latypova, 2013). The liver of experimental birds was characterised by a significant increase in vitamin A content of the liver at various ages (P<0.05). There was an increase in Ca content of the bones of female birds at 15 weeks indicating better Ca reserves for future egg production. Results of balance experiments indicated that females and males of the experimental group were characterised by improved (P<0.05) usage of nitrogen, calcium and phosphorus from the diet. Indeed, usage of the antistress composition with water in period of chicken stress positively affected experimental birds (Shackikh and Latypova, 2014).
The second phase of the experiment was a continuation of the first phase and lasted from day 106 until day 448 and similar to a previous experiment Performax (Magic Antistress Mix) was used with water at 100 g per 100 L of drinking water at days 106–107, 109 –111, 148–157 and 238–246 associated with increased stresses of vaccinations, first egg laying, active egg production growth and peak of egg production (Latypova, 2014b). The main results of egg production are shown in Table 1.
As can be seen from the presented data, usage of the antistress composition with drinking water at specific periods of the increased stress can improve breeder's performance. In particular there was an increase by 2% of the egg peak production and peak plateau lasted about 50 days longer than that in the control birds. It is interesting to note that hen housed egg production in the control group (260.8 eggs) was higher than the target for the line (253.4 
eggs) and in the experimental group it was increased by 6 eggs. Improved egg production was associated with increased weight of the oviduct in the experimental layers (Shackih and Latypova, 2013). It is also important to mention that FCR (feed per 10 eggs) was also improved by usage of the antistress composition and was better than the target for the line. As a result more than 12000 additional eggs were obtained in the experimental group (Latypova and Shackih, 2014). It is interesting to note that egg shell strength at age 26, 36 and 56 weeks was improved in the experimental group by 2.8, 5.6 and 5.6%, respectively. The most interesting finding was related to a significant increase of the carotenoid level in the egg yolk of the experimental birds. Since carotenoids were not supplied with the antistress composition, this increase could be due to improved absorption of nutrients resulting from antistress composition usage. This can also explain improved FCR in the experimental birds. Vitamin A level in the egg yolk from the experimental layers was also increased probably reflecting its transfer from the antistress composition. Antistress composition usage was associated with improved fertility at 16, 40, 48 and 56 weeks by 2.5; 2.7; 2.8 and 3.7%, respectively. In the same experimental group the hatch of condition chickens improved at 26, 32, 40, 48 and 56 weeks by 3.6; 2.1; 3.4; 4.9 and 4.3%, respectively (Latypova, 2014a). In another study with the same antistress composition increased concentrations of the essential amino-acids in the layer's blood were shown (Fotina, 2011). Furthermore, vitamin A concentration in the liver of newly hatched chicks from the experimental group was significantly (P<0.05) increased. During 28-day growth of the hybrid chickens there was a positive effect of the maternal diet on the progeny. In particular, evenness of the birds at day 28 hatched from the eggs of the experimental group at 26, 32, 40, 48 and 56 weeks was improved in comparison to the control group by 14.0; 8.7; 14.4; 7.5 and 11.7%, respectively (Latypova, 2014a; 2014c). A positive effect of the usage of PerforMax (Magic Antistress Mix) was confirmed in a big commercial trial and it was proven that the antistress composition supplied with water can improve hatching egg production efficacy and it is an economically valuable tool to be used in industry (Latypova et al., 2014).
Table 1. Egg production of Hi Line parent laying hens per 64 weeks (Latypova and Shatskikh, 2014)
Molecular mechanisms and new strategies to fight stresses in egg-producing birds - Image 1
Since molecular mechanisms of the stresses are similar in monogastric animals, the vitagene concept of fighting stresses was successfully applied for pigs as well (Surai and Melnichuk, 2012). In particular, using PerforMax (Magic Antistress Mix) for piglets to fight stresses at weaning (Gaponov et al., 2011) and heat stress (Surai and Fotina, 2013) is shown to be effective.
The vitagene concept of fighting stresses emerged as a new direction in a nutritional science. Indeed, by improving the adaptive ability of animals to stress it is possible to substantially decrease negative consequences of various stresses in poultry and farm animal production. The aforementioned data clearly showed that the anti-stress composition developed on the vitagene concept is an effective means in fighting stresses in poultry and pig production.
This article was originally published in Agricultural Science and Technology, Vol. 7, No 1, Pp , 2015.
Antonissen G, Martel A, Pasmans F, Ducatelle R, Verbrugghe E, Vandenbroucke V, Li S, Haesebrouck F, Van Immerseel F and Croubels S, 2014. The impact of Fusarium mycotoxins on humanand animal host susceptibility to infectious diseases. Toxins (Basel), 6, 430-452.
Awad W, Ghareeb K, Böhm J and Zentek J, 2013. Thetoxicological impacts of the Fusarium mycotoxin, deoxynivalenol, in poultry flocks with special reference to immunotoxicity. Toxins (Basel), 5, 912-925.
Battacone G, Nudda A and Pulina G, 2010. Effects of ochratoxin Aon livestock production. Toxins (Basel), 2, 1796-1824.
Buelna-Chontal M and Zazueta C, 2013. Redox activation of Nrf2& NF-κB: a double end sword? Cellular Signalling, 25, 2548-57.
Burkholder KM, Thompson KL, Einstein ME, Applegate TJ and Patterson JA, 2008. Influence of stressors on normal intestinalmicrobiota, intestinal morphology, and susceptibility to Salmonella Enteritidis colonization in broilers. Poultry Science, 87, 1734-1741.
Calabrese V, Cornelius C, Dinkova-Kostova AT, Iavicoli I, Di Paola R, Koverech A, Cuzzocrea S, Rizarelli EA and Calabrese EJ, 2012. Cellular stress responses, hormetic phytochemicals andvitagenes in aging and longevity. Biochimica et Biophysica Acta, 1822, 753-783.
Calabrese V, Cornelius C, Stella AM and Calabrese EJ, 2010. Cellular stress responses, mitostress and carnitine insufficiencies as critical determinants in aging and neurodegenerative disorders: role of hormesis and vitagenes. Neurochemical Research, 35, 1880-1915.
Calabrese V, Calafato S, Puleo E,     Cornelius C, Sapienza M Morganti P and Mancuso C, 2008. Redox regulation of cellularstress response by ferulic acid ethyl ester in human dermal fibroblasts: role of vitagenes. Clinics in Dermatology, 26, 358-363.
Chen Z, Xie J, Wang B and Tang J, 2014. Effect of γ-aminobutyricacid on digestive enzymes, absorption function, and immune function of intestinal mucosa in heat-stressed chicken. Poultry Science, 93, 2490-2500.
De Andrade A, Rogler N, Featherson JC and Allison WRCW, 1977. Interrelationships between diet and elevated temperature (cyclic and constant) on egg production and shell quality. Poultry Science 56, 1178-1188.
Dhama K, Chakraborty S, Verma AK, Tiwari R, Barathidasan R, Kumar A and Singh SD, 2013. Fungal/mycotic diseases of poultry-diagnosis, treatment and control: a review. Pakistan Journal of Biological Sciences, 16, 1626-1640.
Dohms JE and Metz A, 1991. Stress mechanisms ofimmunosuppression. Veterinary Immunology and Immuno-pathology, 30, 89-109.
Ebeid TA, Suzuki T and Sugiyama T, 2012. High ambienttemperature influences eggshell quality and calbindin-D28k localization of eggshell gland and all intestinal segments of laying hens. Poultry Science, 91, 2282-2287.
Elibol O, Peak SD and Brake J, 2002. Effect of flock age, length ofegg storage, and frequency of turning during storage on hatchability of broiler hatching eggs. Poultry Science, 81, 945-950.
Fasenko GM, 2007. Egg storage and the embryo. Poultry Science,86, 1020-1024.
Feddes JJR, Emmanuel EJ and Zuidhof MJ,2002. Broilerperformance, body weight variance, feed and water intake, and carcass quality at different stocking densities. Poultry Science 81, 774-779.
Fisinin VI and Surai PF, 2011. Effective protection from stresses inpoultry production: from vitamins to vitagenes. Poultry and Poultry Products (Ptitza and Ptitzeproducti, Russia) 5, 23-26.
Fisinin VI and Surai PF, 2012a. First days of chicken life: from aprotection against stresses to an effective adaptation. Russian Poultry Science (Ptitsevodstvo, Russia), 2, 11-15.
Fisinin VI and Surai PF, 2012b. Properties and toxicity of DON.Mycotoxins and antioxidants: Uncompromising fighting. Part 1. Animal Production of Russia (Zhivotnovodstvo Rossii), 5, 11-14.
Fisinin VI and Surai PF, 2012c. Properties and toxicity of DON.Mycotoxins and antioxidants: Uncompromising fighting. Part 2. Animal Production of Russia (Zhivotnovodstvo Rossii, Russia), 6, 3-5.
Fisinin VI and Surai PF, 2012d. Mycotoxins and antioxidants:Uncompromising fighting. Ochratoxin A. Part 1. Compounded Feed (Kombikorma, Russia), 3, 55-60.
Fisinin VI and Surai PF, 2012e. Mycotoxins and antioxidants:Uncompromising fighting. Ochratoxin A. Part 2. Compounded Feed (Kombikorma, Russia), 5, 59-60.
Fisinin VI and Surai PF, 2012f. Mycotoxins and antioxidants:Uncompromising fighting. T-toxin – metabolism and toxicity. Part 1. Poultry and Poultry Products (Ptiza i Ptizeproducti, Russia), 3, 38-41.
Fisinin VI and Surai PF, 2012g. Mycotoxins and antioxidants: Uncompromising fighting. T-toxin – mechanisms of toxicity and protection. Part 2. Poultry and Poultry Products (Ptiza i Ptizeproducti, Russia), 4, 36-39.
Fisinin VI and Surai PF, 2013a. Immunity in modern animal andpoultry production: from theory to practical aspects of immunomodulation. Russian Poultry Science (Ptitsevodstvo, Russia), 5, 4-10.
Fisinin VI and Surai PF, 2013b. Gut immunity in birds: facts andthinking. Agricultural Biology (Selskokhozaistvennaya Biologia, Russia), 4, 1-25.
Fotina GA, 2011. Effect of water-soluble antistress compositionFeed Food Magic Antistress on the amino acid composition of the layers blood. Proceedings of the XII Ukranian poultry conference with international participation. Kharkov, pp.307-312
Fotina AA, Fotina TI and Surai PF, 2011. Effect of antistresscomposition Feed-Food Magic Antistress Mix on broiler chicks during growth period. Annals of Sumy National Agrarian University, 2, 158-162.
Fotina A, Fotina TI and Surai PF, 2014. Effect of a water-solubleantistress composition on broiler chickens. Proceedings of the. XIVth European Poultry Conference, p.555, June 23-27, Stavanger, Norway.
Fotina AA, Fisinin VI and Surai PF. 2013. Recent developments inusage of natural antioxidants to improve chicken meat production and quality. Bulgarian Journal of Agricultural Science, 19, 889-896.
Franco-Jimenez DJ, Scheideler SE, Kittok RJ, Brown-Brandl TM, Robeson LR, Taira H, and Beck MM, 2007. Differential effectsof heat stress in three strains of laying hens. The Journal of Applied Poultry Research, 16, 628–634.
Fussell LW, 1998. Poultry industry strategies for control ofimmunosuppressive diseases. Poultry Science, 77, 1193-1196.
Gaponov IV, Fotina TI and Surai PF, 2012. Physiological andtechnological stresses at piglet weaning. Protective effect of the antistress composition. , Svinovodstvo Ukrainy (Pig Production in Ukraine), 13, 6-9.
Georgieva NV, Stoyanchev K, Bozakova N and Jotova I, 2011.Combined effects of muscular dystrophy, ecological stress, and selenium on blood antioxidant status in broiler chickens. Biological Trace Element Research, 142, 532-545.
Grobas S, Mendez J, De Blas C and Mateos GG, 1999. Influenceof dietary energy, supplemental fat and linoleic acid concentration on performance of laying hens at two ages. British Poultry Science, 40, 681–687.
Gunnarsson S, Keeling LJ and Svedberg J, 1999, Effect ofrearing factors on the prevalence of floor eggs, cloacal cannibalism and feather pecking in commercial flocks of loose housed laying hens. British Poultry Science, 40, 12-18.
Hayes JD and Dinkova-Kostova AT, 2014. The Nrf2 regulatorynetwork provides an interface between redox and intermediary metabolism. Trends in Biochemical Sciences, 39, 199-218.
Hoerr FJ, 2010. Clinical aspects of immunosuppression in poultry.Avian Diseases, 54, 2-15.
Howden R, 2013. Nrf2 and cardiovascular defense. OxidativeMedicine and Cellular Longevity, 104308. doi: 10.1155/2013/ 104308. Epub 2013 Apr 4.
Ingrao F, Rauw F, Lambrecht B and van den Berg T, 2013. Infectious Bursal Disease: a complex host-pathogen interaction. Developmental and Comparative Immunology, 41, 429-438.
Johnson RW, Curtis SE and Shanks RD, 1991. Effects on chickperformance of ammonia and heat stressors in various combination sequences. Poultry Science 70, 1132-1137.
Karadas F, Surai PF and Sparks NH, 2011. Changes in broilerchick tissue concentrations of lipid-soluble antioxidants immediately post-hatch. Comparative Biochemistry and Physiology. Part A Molecular & Integrative Physiology, 160, 68-71.
Keum YS and Choi BY, 2014. Molecular and chemical regulation ofthe Keap1-Nrf2 signaling pathway. Molecules, 19, 10074-10089.
Kweider N, Huppertz B, Kadyrov M, Rath W, Pufe T and Wruck CJ, 2014. A possible protective role of Nrf2 in preeclampsia. Annalsof Anatomy, 196, 268-277.
Lai HTL, Nieuwland MGB, Kemp BA, Aarnink JA and Parmentier HK, 2011. Effects of repeated intratracheally administeredlipopolysaccharide on primary and secondary specific antibody responses and on body weight gain of broilers. Poultry Science, 90, 337–351.
Latypova EN, 2014. Efficacy of usage of antistress compositionsVitaminicid and Magic Antistress Mix in egg producing industry. PhD Thesis, Orenburgh, 27 p.
Latypova EN, 2014a. Reproductive performance of egg typebreeders and their progeny quality as affected by antistress compositions. Agrarian Vestnik of the Ural (Russia), 120, 24-31.
Latypova EN, 2014b. Vitaminocid and Magic Antistress Mix in thediet of the egg type breeders. Agrarian Vestnik of the Ural (Russia), 119, 36-40.
Latypova EN, 2014c. Reproductive performance of egg typebreeders and usage of Vitaminicid and Magic Antistress Mix. Glavniy Zootechnick (Ruissia), 4: 36-40.
Latypova  EN,   Shatskikh   EV,   Nesvat   EG,   Surai   PF   and
Zelenskaya OV, 2014. Usage of antistress compositionsVitaminocid and Magic Antistress Mix in egg producing industry: Scientific and practical reccomendations (Russia). Ekaterinburgh, 88p.
Lin H,   Mertens K, Kemps B, Govaerts T, De Ketelaere B,  De Baerdemaeker J, Decuypere E and Buyse J, 2004. Newapproach of testing the effect of heat stress on eggshell quality: Mechanical and material properties of eggshell and membrane. Br. Poultry Science, 45, 476-482.
Lochmiller RL and Deerenberg C, 2000. Trade-offs in evolutionaryimmunology: just what is the cost of immunity? OIKOS, 88, 87–98. Lushchak VI, 2011. Adaptive response to oxidative stress: Bacteria,fungi, plants and animals. Comparative Biochemistry and Physiology. Toxicology and Pharmacology, 153, 175-190.
Ma Q, 2012. Role of nrf2 in oxidative stress and toxicity. AnnualReview of Pharmacology and Toxicology, 53, 401-426.
Ma Q and He X, 2012. Molecular basis of electrophilic and oxidativedefense: promises and perils of Nrf2. Pharmacological Reviews, 64, 1055-1081.
Mack LA, Felver-Gant JN, Dennis RL and Cheng HW, 2013. Genetic variations alter production and behavioral responses following heat stress in 2 strains of laying hens. Poultry Science, 92, 285-294.
Mashaly MM, Hendricks GL, Kalama MA, Gehad AE, Abbas AO and Patterson PH, 2004. Effect of heat stress on productionparameters and immune responses of commercial laying hens. Poultry Science, 83, 889–894.
Majzunova M, Dovinova I, Barancik M and Chan JY, 2013. Redoxsignaling in pathophysiology of hypertension. Journal of Biomedical Science, 20:69. doi: 10.1186/1423-0127-20-69.
Niforou K, Cheimonidou C and Trougakos IP, 2014. Molecularchaperones and proteostasis regulation during redox imbalance. Redox Biology, 2, 323-32. doi: 10.1016/j.redox. 2014.01.017. Collection 2014
Noy Y and Uni Z, 2010. Early nutrition strategy. WPSA Journal, 66,639-646.
Puron D, Santamaria R, Segura JC and Alamilla JL,1995. Broilerperformance at different stocking densities. The Journal of Applied Poultry Research, 4, 55–60.
Sørensen P, Su G and Kestin SC,2000. Effects of age and stockingdensity on leg weakness in broiler chickens. Poultry Science, 79, 864-870.
Quinteiro-Filho WM, Ribeiro A, Ferraz-de-Paula V, Pinheiro ML, Sakai M, Sá LRM, Ferreira AJP and Palermo-Neto J, 2010. Heatstress impairs performance parameters, induces intestinal injury, and decreases macrophage activity in broiler chickens. Poultry Science, 89, 1905-1914.
Rawal S, Kim JE and Coulombe RJr, 2010. Aflatoxin B1 in poultry:toxicology, metabolism and prevention. Research in Veterinary Science, 89, 325-331.
Reczek CR and Chandel NS, 2015. ROS-dependent signaltransduction. Current Opinion in Cell Biology, 33, 8-13.
Safaa HM, Serrano MP, Valencia DG, Frikha M, Jiménez-Moreno E and Mateos GG, 2008. Productive performance and egg quality ofbrown egg-laying hens in the late phase of production as influenced by level and source of calcium in the diet. Poultry Science, 87, 2043-2051.
Sahin N, M. Onderci, Balci TA, Cikim G, Sahin K and Kucuk O, 2007. The effect of soy isoflavones on egg quality and bone mineralization during the late laying period of quail. British Poultry Science, 48, 363-369.
Shatskikh EV and Latypova EN, 2013. The impact of antistressdrugs on the growth and development of the egg type breeding birds. Agrarian Vestnik of the Ural 117, 33-37(Ru).
Shatskikh EV and Latypova EN, 2014. Effect of antistresscompositions on the development of the rearing egg type birds. Ptitzevodstvo (Moscow), 1, 22-27 (Ru).
Shatskikh EV and Latypova EN, 2014a. The development ofinternal organs in the egg type birds under the effects of antistress compositions. Agrarian Vestnik of the Ural (Russia), 122, 35-42 (Ru). Song P and Zou MH, 2014. Redox regulation of endothelial cell fate.Cellular and Molecular Life Sciences, 71, 3219-3239.
Song J, Xiao K, Ke YL, Jiao LF, Hu CH, Diao QY, Shi B and Zou XT, 2014. Effect of a probiotic mixture on intestinal microflora,morphology, and barrier integrity of broilers subjected to heat stress. Poultry Science, 93, 581-588.
Sun X, Zhang H, Sheikhahmadi A, Wang Y, Jiao H, Lin H and Song Z, 2014. Effects of heat stress on the gene expression ofnutrient transporters in the jejunum of broiler chickens (Gallus gallus domesticus). International Journal of Biometeorology, Epub ahead of print] PubMed PMID: 24736810.
Surai PF, 2002. Natural Antioxidants in Avian Nutrition andReproduction. Nottingham University Press, Nottingham, UK. Surai PF, 2006. Selenium in Nutrition and Health. NottinghamUniversity Press, Nottingham, UK.
Surai PF and Dvorska YE, 2005. Effect of mycotoxins onantioxidant status and immunity. In: The Mycotoxin Blue Book (ed. D. Diaz), 93-137, Nottingham University Press, Nottingham. UK.
Surai PF and Fisinin VI, 2012a. Modern methods of fightingstresses in poultry production: from antioxidants to vitagenes. Agricultural Biology (Selskokhozaistvennaya Biologia, Russia), 4, 3-13.
Surai PF and Fisinin VI, 2012b. Feeding breeders to avoidoxidative stress in embryos. Proceedings of the XXIV World's Poultry Congress, Salvador, Bahia, Brazil, on CD-ROM.
Surai PF and Fisinin VI, 2013. Natural antioxidants in hens'embryogenesis and antistress defence in postnatal development. Agricultural Biology (Selskokhozaistvennaya Biologia, Russia), 2, 3-18.
Surai PF and Fotina TI, 2013. Physiological mechanisms of theheat stress development in poultry. Today's Animal Production (Ukraine), 6, 54- 60.
Surai PF and Fotina TI, 2013. Physiological mechanisms andpractical approaches to decrease detrimental consequences of heat shock in pig production. Svinarstvo Ukraini (Pig Production in Ukraine), 25, 12-15.
Surai PF, Fotina AA and Fotina TI, 2012. Effect of Feed Food MagicAntistress Mix on natural disease resistance of ducklings. Annals of Sumy National Agrarian University (Ukraine), 7, 58-61.
Surai PF and Melnichuk SD, 2012. Mechanisms of Anti-StressProtection in Pig Farming. From Vitamins to Vitagenes, Svinovodstvo Ukrainy (Pig Production in Ukraine), 2, 10-15.
van der Wijst MG, Brown R and Rots MG, 2014. Nrf2, the masterredox switch: The Achilles' heel of ovarian cancer? Biochimica et Biophysica Acta, 1846, 494-509.
Velichko O and Surai P, 2014. Effect of an antistress composition supplied with water on chick growth and development. Proceedings of the XIVth European Poultry Conference, 551, 23-27 June 23-27, Stavanger, Norway.
Velichko OA, Shabaldin SA and Surai PF, 2013. Practical aspectsof usage of vitagenes concept in poultry production. Russian Poultry Science (Ptitsevodstvo, Russia), 4, 42- 45.
Wani R, Nagata A and Murray BW, 2014. Protein redox chemistry:post-translational cysteine modifications that regulate signal transduction and drug pharmacology. Frontiers in Pharmacology, 224. doi: 10.3389/fphar.2014.00224.
Yang XJ, Li WL, Feng Y and Yao JH, 2011. Effects of immunestress on growth performance, immunity, and cecal microflora in chickens. Poultry Science, 90, 2740-2746.
Zhang PY, Xu X and Li XC, 2014. Cardiovascular diseases:oxidative damage and antioxidant protection. European Review for Medical and Pharmacological Sciences, 18, 3091-3096.
Zhou S, Sun W, Zhang Z and Zheng Y, 2014. The role of Nrf2-mediated pathway in cardiac remodeling and heart failure. Oxidative Medicine and Cellular Longevity, 260429. doi: 10.1155/2014/ 260429.
Related topics:
Prof. Stefan Denev, DSc., PhD.
Peter Surai
Scottish Agricultural College - SAC
Youssef Attia
26 de diciembre de 2019
Water supplements are more effective than in feed supplies due to many well known factors affecting feed intake praticulary during heat stress. The response to organic ligands depends on mineral status of the feeds as said.
Juarez Donzele
Universidade Federal de Viçosa - UFV
16 de diciembre de 2019

Dr. Peter, thank you for the clarification. However, I would like to make clear that it was precisely because of the effects of these factors on free radical production, which is the object of study, that I made the considerations. For example, it is known that decreasing CPU expression, as it results in an increase in mitochondrial proton gradient, increases free radical production. These are different approaches, one protecting cells from oxidative stress by stimulating increased antioxidant factors and the other protecting cells by interfering with the activities of factors that cause increased free radical production. The question is which of the two factors would be most efficient.

Juarez Donzele
Universidade Federal de Viçosa - UFV
16 de diciembre de 2019
Dr Peter, excellent insightful story about the favorable action of possible nutritional agents to mitigate the negative effects of heat stress on monogastric performance. Taking advantage of the knowledge of the research team involved in the work, I would like to ask a question. Specifically in birds exposed to high temperatures, it would also not be important to evaluate the expression of mitochondrial uncoupling protein (UCP), whose activity decreases, and corticosterone hormone, which increases, precisely due to its recognized actions in the production of free radicals.
Peter Surai
Scottish Agricultural College - SAC
17 de julio de 2017
Thank you for comments, I would like to stress the following: 1. Organic minerals will not solve the problem of the stress, their supplementation is effective only in the case of dietary mineral (Zn, Mn, Cu, Se) deficiency. If the diet is adequate in these minerals, there would not be much response in terms of antioxidant enzyme synthesis. The technology of supplying special vitagene-regulating mixture is dealing with improvement of adaptive ability of animals in stress conditions. This technology is considered to be " a fast-reacting tool" in the hand of nutritionist/technologists to deal with stressful situations in commercial poultry/animal production. Indeed, such situations are very often unpredictable and the usage of feed supplements in such situations has a low flexibility (one have to finish the feed in the feed bin, before anything can be added via feed). In contrast to this, usage the supplement with water gives an opportunity of fast reacting. 2. As for usage of such technology in industry, it is widely used worldwide, including Russia, Ukraine, Kazakhstan, Moldova, Egypt, Turkey, Thailand, Taiwan, etc. Such a tool helps in various stressful situations, from heat stress to mycotoxicosis, from immunosuppression to post-vaccinal stress, etc.
Talaat Mostafa  El-Sheikh
20 de diciembre de 2016
It is a wonderful article and opens up new aspect of using anti stress factors in laying stocks
Tanaji Valmik Lokare
19 de diciembre de 2019
Its very interesting topic will help in layer farmer for keeping their farm healthy in critical situation and to produce better quality of eggs.
Ismet Mamode
Food & Allied Group of Companies
27 de diciembre de 2016
It is a very interesting research work which has a great importance in the field. How many farms are implementing the recommendations of the project and what are their results?
Tahir Mahmood
Tahir Mahmood
20 de diciembre de 2016
It is a wonderful article and opens up new aspect of handling oxidative stress in poultry. The authors mentioned that during stress, the feed intakes of birds dropped and that's why antistress mix supplied in water becomes more helpful in combating the stress. My point is, why not we include some organic mineral which are part of antioxidant defense mechanism of the bird body and lets not develop stress to a level where feed intake is dropped. I personally believe, providing some organic minerals/vitamins especially Selenium in feed could be more effective than water soluble supplements.
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