Garlic: An Alternative to Antibiotics in Poultry Production, A Review

Iranian Journal of Applied Animal Science

مقاله 2، دوره 8، شماره 1، خرداد 2018، صفحه 9-17   

نوع مقاله: Review Articles

نویسندگان

B. Navidshad^{* 1}؛ B. Darabighane¹؛ M. Malecky²

¹Department of Animal Science, University of Mohaghegh Ardabili, Ardabil, Iran

²Department of Animal Science, Bu Ali Sina University, Hamedan, Iran

چکیده

In last decade, the uncontrolled use of antibiotics as growth promoter for livestock has led to the appearance of antibiotic-resistant pathogens and increased risk of infectious diseases. This situation has triggered intensive research efforts to find safe alternative strategies. Certainly, the plants and vegetables and their derivatives as natural safe substances could be good candidates in this respect. There is huge information on the immunostimulatory properties of herbal plans in human, and may contribute considerably to the improvement of the health and immune response and prevention of certain diseases in animals including poultry. Garlic (Allium sativum) is an herbal plant that has traditionally been used for the healing a number of human diseases and has in recent years been revealed to have immunostimulatory, anticardiovascular disease, antitumour, antioxidant and antimicrobial properties. The scientific evidences suggest that allicin and other active components of garlic have also some positive effects for livestock, including hypocholesterolemic, growth promoting, antimicrobial and antioxidant effects.

کلیدواژه‌ها

broilers؛ Garlic؛ immunological responses؛ layer hens؛ serum lipids

اصل مقاله

INTRODUCTION

Antibiotic treatments have been the most successful way to control infection and reduce mortality in humans and animals. However, the increasing use of antibiotics especially as growth promoters for livestock has led in a significant risk of microbial resistance. At present, the World Health Organization is recommending producers to apply alternative ways to antibiotics to prevent and treatment of infectious diseases (Lowenthal et al. 1999). On the other hand, while certain infectious diseases have been effectively prohibited by vaccination, it seems that vaccine efficiency has reduced alongside with a raise in virulence of antigens, and some of these are capable of break through vaccination immunity (Lien et al. 2007; Wu et al. 2008). With the ban of the use of antibiotics as growth promoters in last decade in most countries, attention has focused into finding alternatives ways that do not have the problems associated with antibiotics. Research interest has been focused on herbal plants that are reported to possess various therapeutic properties. This natural and safe source of active substances has been attractive research subjects over the past decades and has led to promising results (Masihi, 2002; Okamura et al. 2004; Sampedro et al. 2004; Jayaprakasha et al. 2006). Phytobiotics, or phytogenic substances, are usually safe natural plant derivatives which as feed additives could improve the health and performance of animals (Windisch et al. 2008). Garlic (Allium sativum) is commonly used as either a flavoring agent for food or as traditional therapeutic agent for the treatment of different diseases (Essman, 1984; Konjufca et al. 1997; Amagase et al. 2001; Sallam et al. 2004). Animal studies have showed that garlic has hypolipidemic, hypotensive, hypoglycemic, hypothrombotic, and hypoatherogenic effects (Bordia et al. 1975; Shoetan et al. 1984). As said by folk medication, garlic is effective to healing cardiac disease (Essman, 1984). Although there are numerous publications on the hypocholesterolemic effects of garlic in humans (Silagy and Neil, 1994; Warshafsky et al. 1993), however, it has suggested that commercially available garlic products may not be hypocholesterolemic (Berthold et al. 1998). It could be because of the differences in preparation procedures, the stability of effective components, and the period of the study (Amagase et al. 2001). Compared with human studies, there is relatively limited information on the use of phytonutrients in general, and garlic in particular, in poultry veterinary medicine. The objective of this review was to summarize the recent findings on the impact of garlic and its derivatives as feed additives on performance, immune system as well as lipid metabolism in broiler chickens and layer hens.

 

Garlic active compounds

The flavonoid and organosulphur components of garlic and garlic derivatives have been shown to have therapeutic and antioxidant effects in both broilers and layer hens (Chowdhury et al. 2002; Sallam et al. 2004). The therapeutic properties of garlic are mainly attributed to the thiosulfinates, the single most abundant group of sulphur containing compounds (Calvo-Gómeza et al. 2004; Lanzotti, 2006). Garlic have at least 33 sulphur-containing substances, several enzymes, 17 amino acids, and trace minerals for example selenium (Newall et al. 1996). Allicin (of which allin is the precursor) is the main sulphurcontaining component and usually consists more than two third of the total thiosulfinates (about 4 g/kg fresh mass). Allicin is formed when slicing or crushing the fresh garlic and breaks the intercellular compartments which separate alliin and alliinase (Lawson, 1998; Rybak et al. 2004). Allicin is unstable and poorly absorbable (Lawson and Wang, 2001). On the other hand, garlic derivatives which are produced by means of heating or solvent extraction methods are usually contain alliin, however also are free of allinase; therefore, no allicin may be found in the final product. The oil and steam-distilled derivatives are usually rich in secondary metabolites for example ajoene, but there is no scientific approve on the comparable chemical characteristics of these secondary active compounds in fresh garlic (Newall et al. 1995). The another important compound of garlic is inulin and the decreased digesta pH of birds fed garlic could be attributed to higher volatile fatty acids production because of the prebiotic effects of inulin and its hydrolysates which may help to overcome of useful microbes colonization (Grajek et al. 2005). Nuutila et al. (2003) reported that garlic husk had higher total phenolics than garlic bulb. It seems that these active pharmacological components act on several intracellular signaling pathways.

 

Immunomodulatory properties of garlic

It would seem that dietary garlic, at suitable dosages, has a positive effect on functions of the immune system, and could offer a future alternative way in the control of chicken diseases. However the previous reports in on the effects of garlic on chicken immune system responses were not always supportive. For instance, Szigeti et al. (1998) found that garlic supplement in broilers augmented antibody production against Newcastle disease virus (NDV), while Jafari et al. (2008) observed no beneficial effects on antibody production following 1% or 3% garlic consumption in diet. Hanieh et al. (2010) showed that the 3% dietary garlic had less stimulatory effect on immune response, and in some cases the antibody titers were considerably lesser to those at a lower dietary level. They reported that garlic treatment increased lymphocyte proliferation, white blood cells (WBC) count and the relative weights of spleen and thymus of broiler chickens. The effect of garlic supplement on increases in the size of the spleen, bursa fabricius and thymus of chickens are probably attributed to the more lymphocyte proliferation and the increase in WBC counts (Hanieh et al. 2010). Garlic supplementation increased withe blood cells counts in blood stream of the chickens in the study of Hanieh et al. (2010). However, Jafari et al. (2008) have observed that garlic does not affect leukocyte numbers in broilers. The increased lymphocyte proliferation in company with the potential protection of the cells from oxidative stress suggested to contribute for the increased with blood cells count by garlic supplementation (Hanieh et al. 2010). Hanieh et al. (2010) also studied the effects of dietary garlic on immune responses in White Leghorn chicken. Garlic at 10 g/kg diet increased anti-NDV, anti-SRBC and anti- Brucella abortus (BA) antibody productions, while 30 g/kg diet had less stimulatory effects. They also found an increased splenocyte and thymocyte proliferations in garlic fed chickens. Macrophage activation is necessary to establish control of infection and progression of certain diseases. Dorhoi et al. (2006) also have reported that supplementation garlic extract to a macrophage culture of laying hens at 50 mg/mL tended to increase sheep red blood cell (SRBC) uptake; on the other hand, high dosage of the extract (200 mg/mL) inhibited phagocytosis. Ghazanfari et al. (2000) showed that immunostimulatory properties injection of garlic extract or its protein fraction augmented parasite engulfment and destruction in peritoneal macrophages. Hanieh et al. (2012) in an in vitro study, showed that garlic extract increased concanavalin A (ConA)-induced splenocytes (4, 8 and 16 mg/mL) and thymocytes (2, 4 and 8 mg/mL) proliferations, and gene expression of IL-2 (8 and 16 mg/mL) and interferon (INF)-g (16 mg/mL). Macrophages also exhibited superior microbicidal activity and reactive oxygen species (ROS) production with garlic extract at 4 and 8 mg/mL. These authors suggested that it is likely that garlic has direct stimulatory effects on immune cell functions. Kyo et al. (1999) found that supplementation of garlic extract to a culture increased the production of IL-2, IL-12, INF-γ and tumor necrosis factor (TNF)-α in stimulated splenocytes. Feng et al. (1994) showed that diallyl trisulfide, one of the main sulphur compounds of garlic, at lower concentrations of 3-12.5 mg/mL increased the proliferative responses in a culture stimulated with ConA, whereas at higher concentration of 50 mg/mL inhibited T-lymphocyte proliferation in mice. Hanieh et al. (2010) suggested that the stimulatory effects of garlic on humoral immune response maybe because of the improved immune cell functions that is cytokine production and / or antigen presenting cells phagocytic capacity. Oxidative stress is a potential factor coupled with the immune response itself (Costantini and Møller, 2009). Thus, the antioxidative properties of garlic might have resulted to the improved functioning of the immune cells by protecting them from oxidative stress. Although Alliumplants may be valuable to health, the toxicity of these vegetables has been also reported in domestic (Stevens, 1984; Rae, 1999; Van der Kolk, 2000) and laboratory (Munday et al. 2003) animals. It is reported that high concentration of garlic extract (200 mg/mL) impairs phagocyte function (Dorhoi et al. 2006).

 

Antimicrobial effect of garlic

Phytobiotics may reduce growth of pathogenic microbes, thus providing a balance of gut microflora. Most of the studies on the use of antibiotic growth promoter alternatives have focused on their antimicrobial activities. The active compound in garlic, allicin, has well known antimicrobial properties (Ankri and Mirelman, 1999; Kim et al. 2013) and decrease gut pathogenic populations. Garlic also showed antiviral (Ankri and Mirelman, 1999), antibacterial (Kumar and Berwal, 1998; Ankri and Mirelman, 1999; Sivam, 2001), antifungal and antiparasitic (Ankri and Mirelman, 1999) activities. Hanieh et al. (2010) reported that dietary garlic has a stimulatory effect on antibody production against gram-negative bacterial antigen in White Leghorn chickens. Garlic has been recommended for the treatment of parasitoses and other intestinal diseases (Iciek et al. 2009). Crude extracts of garlic decreased or eliminated Hymenolepis, Aspiculuris, Histomonas and Eimeria parasites in animal models of infection (Ayaz et al. 2008; Dkhil et al. 2011).

 

Hypocholesterolemic effects of garlic

One of the well known therapeutic properties of garlic is its hypocholesterolemic effect. This effect has reported in chicken too (Essman, 1984; Warshafsky et al. 1993; Silagy and Neil, 1994; Chowdhury et al. 2002). Sklan et al. (1992) reported lower hepatic cholesterol concentrations in chickens fed 2% garlic 14 d. In the study of Choi et al. (2010), increasing the levels of garlic meal and using garlic meal plus α-tocopherol considerably reduced total and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol in broiler blood. Konjufca et al. (1997) also reported that 3% dietary garlic meal decreased plasma cholesterol and breast and thigh muscle cholesterol in broilers. In the study of Choi et al. (2010), the supplementation with 5% garlic meal or 3% garlic meal plus α-tocopherol significantly decreased total and low density lipoproteins (LDL) levels and increased high density lipoproteins (HDL) levels compared with the control. They explained this finding by the reduction of synthetic enzyme activity. Garlic or garlic plus –tocopherol would be expected to have a much higher antioxidant power or biological effects, among which are reducing the production of free radicals (Chowdhury et al. 2002). In the study of Sharma et al. (1979) egg yolk cholesterol was decreased by feeding 1 or 3% garlic meal to laying hens for 3 wk. Yalcin et al. (2006), reported that 0.5 and 1% dietary garlic decreased egg yolk cholesterol and serum triglyceride without negative effects on performance and egg traits of laying hens. Garlic paste (3.8%), solvent fractions, or garlic oil equal to this quantity decreased serum cholesterol by 18 and 23% in broilers and 12-wk-old Leghorn pullets (Qureshi et al. 1983b). Comparable findings have been reported in laying hens and broiler chicks fed 2, 4, 6, 8, or 10% garlic meal and supplementation with 200 or 400 IU of α-tocopherol (Chowdhury et al. 2002; Kim et al. 2006). Chowdhury et al. (2002) concluded that up to 8% supplemental sun-dried garlic paste decreased serum and yolk cholesterol concentrations and can be used as a hypocholesterolemic agent in practical layer diets. Qureshi et al. (1983a) found lower activities of hydroxymethylglutaryl-coenzyme A reductase, cholesterol 7 α-hydroxylase, and fatty acid synthetase when chickens were supplemented with polar fractions of garlic powder (garlic equivalent to 1, 2, 4, 6, and 8% fresh garlic paste) for 3 weeks. However there are some reports on the ineffectiveness of dietary garlic or its extract on serum or yolk cholesterol concentration. In a study, this cholesterol reducing effect of garlic was not observed in the yolk and serum of laying hens fed 3% garlic meal (Birrenkott et al. 2000). Birrenkott et al. (2000), also found that 3% garlic meal did not change yolk and serum cholesterol concentrations when laying hens were fed diets for 8 month. Egg yolk cholesterol concentrations have been reported to vary depending on the genetic strain of the laying hens (Han and Lee, 1992). Reddy et al. (1991) have reported that 0.02% garlic oil did not have any significant effect on serum cholesterol. Lim et al. (2006) also observed that the level of HDL was not changed by 0, 1, 3, or 5% dietary garlic meal in laying hens. The contradictory reports on the effects of garlic on serum and yolk cholesterol could be due to use of different commercial garlic products. It has suggested that some commercial garlic oil, garlic meal, and commercially available garlic extract may not be hypocholesterolemic (Berthold et al. 1998). The different garlic products may be allicin-rich which made from raw garlic or nonallicin-rich which is produced from processed garlic. These products may differ significantly in hypocholesterolemic effects.

 

Effect of garlic supplementation on broiler performance

There are considerable efforts to introduce garlic as an effective growth promoter for broiler chickens and the most reports have indicated promising outcomes (Javed et al. 2009; Aji et al. 2011). However the differences in the experimental conditions, birds genetic and health status as well as the type, processing and quality of garlic products have resulted in some controversial recommendations. Shi et al. (1999) fed 0.2, 1 or 2% garlic meal to broilers and found the best performance in birds fed 1% garlic meal. In a comparable report, Javandel et al. (2008) supplemented broiler’s diets with 0, 0.125, 0.25, 0.5, 1 or 2% garlic meal. The diets containing less than 2% garlic meal improved growth rate and feed conversion ratio (FCR) compared to the control group. However the 2% dietary garlic meal apparently had adverse effects on broiler performance. Jagdish and Pandey (1994) reported a different effective dosage such that a lower FCR was found with 0.25% garlic meal in compare to control group and 0.5% level. However, Qureshi et al. (1983b) found no differences in growth performance of broilers up to 5% garlic meal, and in the study of Horton et al. (1991) there was no improvement in the performance of broilers fed 0, 0.01, 0.1 or 1% garlic meal. Reddy et al. (1991) and Chowdhury et al. (2002) also reported that the sun-dried garlic meal and garlic oil did not affect growth performance. The inconsistency in results may be because of differences in experimental diets and birds, and the quality and quantity of the active components in the garlic product. Some researchers tried to combine the garlic and other feed additives to achieve more benefits. Choi et al. (2010) fed broilers diet treatments containing 0, 1, 3, and 5% garlic meal and 3% garlic powder + 200 IU of α-tocopherol/kg and did not observe any difference in broiler’s performance, but the mixture of garlic powder and α-tocopherol supplements increased crude protein, decreased crude fat contents of carcass and also reduced the pH and thiobarbituric acid (TBA) reactive substances values of chicken meat. In experiment of Olukosi and Dono (2014), the garlic meal in combination with turmeric meal at the rate of 10 g/kg each decreased digesta pH in the crop, proventriculus and ceca, and improved ileal digestible and apparent metabolisable energy but had no effect at the jejunum. The outcome of these changes was improved weight gain and FCR compared to the control group. Adibmoradi et al. (2006) reported positive changes in the small intestine morphology of broilers fed garlic meal which resulted in an improved performance. The increased villi heights enhance nutrient absorption because of higher surface area, while deeper crypt can represent increased cell turnover in response to normal cellular sloughing or inflammatory situation. A combination of longer villi and deeper crypt is a sign of a healthy intestinal development in response to the use of the garlic additive. The antioxidant properties of garlic may improve growth and development of birds the digestive tract overall gut function (Halliwell et al. 2000). The enhanced gut function improves nitrogen energy utilization. The lower pH of digesta in birds fed garlic meal may be an indication of the prebiotic effect which was resulted in more volatile fatty acid (VFA) production and supports the proliferation of beneficial microbes (Yang et al. 2009). Because the most part of the compounds reach to hind gut fermentation are ingested carbohydrates and protein that escape foregut digestion (Cummings, 1985; Cummings and Macfarlane, 1991), better foregut digestion will improve nutrient utilization for the host and decrease harmful microbes colonization in the gut. Varmaghany et al. (2015) studied the effects of dietary garlic at 0, 0.5, 1.0 or 1.5% dosage on hematological parameters, ascites incidence, and growth performance of an ascites susceptible broiler hybrid under both standard and cold temperature conditions. The final body weight decreased, with increasing dietary garlic in the standard temperature, however the FCR did not affect among all groups under both temperature conditions. They concluded that the 0.5% dietary garlic meal effectively decreased systemic hypertension and prevalence of ascites without any negative effects on broiler chicken performance. Tables 1 and 2 have summarized the reports on the garlic or garlic products effects on the chicken performance and meat characteristics. Thiobarbituric acid reactive substances (TBARS) - are a sign of lipid peroxidation and can be measured using thiobarbituric acid as a reagent.

 

Table 1 The summary of reports on the effects of garlic or garlic products on chickens feed intake and weight gain as a percentage of control group

M: male and F: female.

 

Table 2 The summary of reports on the effect of garlic and garlic products on the chicken meat characteristics

M: male and F: female.

L*: lightness; a*: yellowness; b*: redness; WHC: water-holding capacity and TBARS: thiobarbituric acid reactive substances.

 

As reactive oxygen species (ROS) have very short half-lives, they are complex to determine directly. As an alternative, TBARS are measured as an oxidative stress indicator (Pryor, 1991).

 

Laying hen performance

In the study of Yalcin et al. (2006), the diets containing 0.5 or 1% garlic meal increased egg weight without adverse effects on performance and egg traits of laying hens. However, in another study, Yalcin et al. (2007) found that body weight, feed intake, and feed conversion ratio were not influenced by the dietary garlic. These authors suggested that the strong odor of garlic does not act as a deterrent of feeding. Reddy et al. (1991) observed that egg production; egg mass, body weight, feed consumption, and feed efficiency were not affected during the 8 weeks that 0.02% garlic oil was fed to the Babcock B-300 strain. Chowdhury et al. (2002) evaluated the effect of dietary garlic on overall performance in different layer hen strains. Thirty-six, 28-wk-old, Hisex Brown, Isa Brown, Lohmann, Starcross, Babcock, and Starcross-579 strains were fed diets containing 0, 2, 4, 6, 8 or 10% sun-dried garlic meal for 6 weeks. They found no differences among diets or strains in egg weight, egg mass, feed consumption, feed efficiency, and body weight gain over 6 weeks. Yolk weight, however, responded quadratically with increasing levels of dietary garlic. Organoleptic effects of garlic also have evaluated. Birrenkott et al. (2000), found no differences in color and flavor in eggs from hens consuming up to 3% dietary garlic powder.

 

CONCLUSION

Herbal plants have considerable promise in health promoting effects in poultry, and because of the these substances are considered as potential alternatives to antibiotics, there is no time delay for discovering and testing their therapeutic properties. In general the majority of the data generated from evaluation of garlic and garlic derivatives in poultry, have confirmed improvement in performance, cholesterol reduction in blood and products and also antimicrobial properties. Therefore, garlic show promising potential for applications in organic and conventional poultry production. However, there are data gaps which need to be filled. Due to the complexity of the active compounds of garlic, a concentration is needed in order to find the best usage recommendation in different category of poultry.

مراجع

Abdullah A.Y., Mahmoud K.Z., Nusairat B.M. and Qudsieh R.I. (2010). Small intestinal histology, production parameters, and meat quality as influenced by dietary supplementation of garlic (Allium sativum) in broiler chicks. Italian J. Anim. Sci. 9, 414-419.

Adibmoradi M., Navidshad B., Seifdavati J. and Royan M. (2006). Effect of dietary garlic meal on histological structure of small intestine in broiler chickens. J. Poult. Sci. 43, 378-383.

Aji S.B., Ignatuius K., Ado A.Y., Nuhu J.B. and Abdulkarim A. (2011). Effect of feeding onion (Allium cepa) and garlic (Allium sativum) on some performance characteristics of broiler chickens. Res. J. Poult. Sci. 4, 22-27.

Amagase H., Petesch B.L., Matsuura H., Kasuga S. and Itakura Y. (2001). Intake of garlic and its bioactive components. J. Nutr. 131, 955-962.

Ankri S. and Mirelman D. (1999). Antimicrobial properties of allicin from garlic. Microb. Infect. 1, 125-129.

Ao X., Yoo J.S., Zhou T.X., Wang J.P., Meng Q.W., Yen L., Cho J.H. and Kim I.H. (2011). Effects of fermented garlic powder supplementation on growth performance, blood profiles and breast meat quality in broilers. Livest. Sci. 141, 85-89.

Ayaz E., Turel I., Gul A. and Yilmaz O. (2008). Evaluation of the anthelmentic activity of garlic (Allium sativum) in mice naturally infected with Aspiculuris tetraptera. Rec. Pat. Antiinfect. Drug Discov. 3, 149-152.

Berthold H.K., Sudhop T. and Von Bergmann K. (1998). Effect of a garlic oil preparation on serum lipoproteins and cholesterol metabolism: A randomized controlled trial. J. Am. Med. Assoc. 279, 1900-1902.

Birrenkott G., Brockenfelt G.E., Owens M. and Halpin E. (2000). Yolk and blood cholesterol levels and organoleptic assessment of eggs from hens fed a garlic-supplemented diet. Poult. Sci. 79(1), 75-82.

Bordia A., Bansal H.C., Arora S.K. and Singal S.V. (1975). Effect of the essential oils of garlic and onion on alimentary hyperlipemia. Atherosclerosis. 21, 15-18.

Calvo-Gómeza O., Morales-López J. and López M. (2004). Solid-phase microextraction–gas chromatographic–mass spectrometric analysis of garlic oil obtained by hydrodistillation. J. Chromatograph A. 1036, 91-93.

Choi H., Park W.Y. and Kim Y.J. (2010). Effects of dietary garlic powder and α-tocopherol supplementation on performance, serum cholesterol levels, and meat quality of chicken. Poult. Sci. 89, 1724-1731.

Chowdhury S.R., Chowdhury S.D. and Smith T.K. (2002). Effects of dietary garlic on cholesterol metabolism in laying hens. Poult. Sci. 81, 1856-1862.

Costantini D. and Møller A. (2009). Does immune response cause oxidative stress in birds? A meta-analysis. Comp Biochem. Physiol. 153, 339-344.

Cross D.E., Acamovic T., Deans S.G. and Mcdevitt R.M. (2002). The effect of dietary inclusions of herbs and their volatile oils on the performance of growing chickens. Br. Poult. Sci. 43, 33-35.

Cummings J.H. (1985). Diet and short chain fatty acids in the gut. Pp. 78-93 in Food and the Gut. J.O. Hunter and V.A. Jones, EDs. Bailliere Tindall, London, United Kingdom.

Cummings J.H. and Macfarlane G.T. (1991). The control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol. 70, 443-459.

Dehkordi S., Zamani Moghadam A., Maghsoudi N., Aali E., Gerami R. and Dehsade Ghi E. (2010). The effects of fresh garlic on the serum concentration of total cholesterol, total triglyceride and adipose tissues of broilers. Biochim. Biophys. Acta. 19, 363-365.

Dkhil M.A., Abdel-Baki A.S., Wunderlich F., Sies H. and Al-Quraishy S. (2011). Anticoccidial and antiinflammatory activity of garlic in murine Eimeria papillata infections. Vet. Parasitol. 175, 66-72.

Dorhoi A., Dobrean V., Zahan M. and Virag P. (2006). Modulatory effects of several herbal extracts on avian peripheral blood cell immune responses. Phytother. Res. 20, 352-358.

Essman E.J. (1984). The medical uses of herbs. Fitoterapia. 55, 279-289.

Feng Z., Zhang G., Hao T., Zhou B., Zhang H. and Jiang Z. (1994). Effect of diallyl trisulfide on the activation of T cell and macrophage-mediated cytotoxicity. J. Tongj Med. Univ. 14, 142-147.

Ghazanfari T., Hassan Z., Ebtekar M., Ahamdiani A., Naderi G. and Azar A. (2000). Garlic induces a shift in cytokine pattern in Leishmania major-infected Balb/c mice. Scandinavian J. Immunol. 52, 491-496.

Grajek W., Olejnik A. and Sip A. (2005). Probiotics, prebiotics and antioxidants as functional foods. Acta. Biochim. Pol. 52, 665-671.

Halliwell B., Zhao K. and Whiteman M. (2000). The gastrointestinal tract: A major site of antioxidant action? Free Radic. Res. 33, 819-830.

Han C.K. and Lee N.H. (1992). Yolk cholesterol content in eggs from the major domestic strains of breeding hen. Asian-Australasian J. Anim. Sci. 5, 461-464.

Hanieh H., Narabara K., Piao M., Gerile C., Abe A. and Kondo Y. (2010). Modulatory effects of two levels of dietary Alliums on immune response and certain immunological variables, following immunization, in White Leghorn chicken. Anim. Sci. J. 81, 673-680.

Hanieh H., Narabara K., Tanaka Y., Gu Z., Abe A. and Kondo Y. (2012). Immunomodulatory effects of Alliums and Ipomoea batata extracts on lymphocytes and macrophages functions in White Leghorn chickens: In vitro study. Anim. Sci. J. 83, 68-76.

Horton G.M.J., Fennell M.J. and Prasad B.M. (1991). Effects of dietary garlic (Allium sativum) on performance, carcass composition and blood chemistry changes in broiler chickens. Canadian J. Anim. Sci. 71, 939-942.

Iciek M., Kwiecien I. and Wlodek L. (2009). Biological properties of garlic and garlic-derived organosulfur compounds. Environ. Mol. Mutagen. 50, 247-265.

Jafari R., Razi M., Ghorbanpoor M. and Marashian S. (2008). Effect of dietary garlic on immune response of broiler chicks to live Newcastle disease vaccine. Pakistan J. Biol. Sci. 14, 1848-1851.

Jagdish P. and Pandey R.C. (1994). Effect of different levels of garlic inclusion in the ration of cockerels in their growth rate and feed conservation ratio. Poult. Adv. 27, 39-41.

Javandel F., Navidshad B., Seifdavati J., Pourrahimi G.H. and Baniyaghoub S. (2008). The favorite dosage of garlic meal as a feed additive in broiler chickens ration. Pakistan J. Biol. Sci. 11, 1746-1749.

Javed M., Durrani F., Hafeez A., Khan R.U. and Ahmad I. (2009). Effect of aqueous extract of plant mixture on carcass quality of broiler chicks. J. Agric. Biol. Sci. 4, 37-40.

Jayaprakasha G., Negi P. and Jena B. (2006). Antioxidative and antimutagenic activities of the extracts from the rinds of Garcinia pedunculata. Innov. Food Sci. Emerg. Technol. 7, 246-250.

Jimoh A.A., Ibitoye E.B., Dabai Y.U. and Garba S. (2013). In vivo antimicrobial potentials of garlic against Clostridium perfringens and its promotant effects on performance of broiler chickens. Pakistan J. Biol. Sci. 16, 1978-1984.

Kim B.C., Ryu Y.C., Cho Y.J. and Rhee M.S. (2006). Influence of dietary α-tocopheryl acetate supplementation on cholesterol oxidation in retail packed chicken meat during refrigerated storage. Biosci. Biotechnol. Biochem. 70, 808-814.

Kim Y.J., Jin S.K. and Yang H.S. (2009). Effect of dietary garlic bulb and husk on the physicochemical properties of chicken meat. Poult. Sci. 88, 398-405.

Kim D.K., Lillehoj H.S., Lee S.H., Lillehoj E.P. and Bravo D. (2013). Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites. Br. J. Nutr. 109, 76-88.

Kirkpinar F., Ünlü H.B., Serdaroğlu M. and Turp G.Y. (2014). Effects of dietary oregano and garlic essential oils on carcass characteristics, meat composition, colour, pH and sensory quality of broiler meat. British Poult. Sci. 55(2), 157-166.

Konjufca V.H., Pesti G.M. and Bakalli R.I. (1997). Modulation of cholesterol levels in broiler meat by dietary garlic and copper. Poult. Sci. 76, 1264-1271.

Kumar M. and Berwal J. (1998). Sensitivity of food pathogens to garlic (Allium sativum). J. Appl. Microbiol. 84, 213-215.

Kyo E., Uda N., Ushijima M., Kasuga S. and Itakura Y. (1999). Prevention of psychological stress-induced immune suppression by aged garlic extract. Phytomedicine. 5, 325-330.

Lanzotti V. (2006). The analysis of onion and garlic. J. Chromatograph. A. 1112, 3-22.

Lawson L.D. (1998). Garlic: A review of its medicinal effects and indicated active compounds. Pp. 176-209 in Phytomedicines of Europe: Chemistry and Biological Activity. L.D. Lawson and R. Bauer, Eds. American Chemical Society, Washington, D.C., USA.

Lawson L.D. and Wang Z.J. (2001). Low allicin release from garlic supplements: A major problem due to the sensitivities of alliinase activity. J. Agric. Food Chem. 49, 2592-2599.

Lim K.S., You S.J., An H.K. and Kang C.W. (2006). Effects of dietary garlic powder and copper on cholesterol content and quality characteristics of chicken eggs. Asian-australasian J. Anim. Sci. 19, 582-586.

Lien Y., Lee J., Su H., Tsai H., Tsai M., Hsieh C. and Tsai S. (2007). Phylogenetic characterization of Newcastle disease viruses isolated in Taiwan during 2003-2006. Vet. Microbiol. 123, 194-202.

Lowenthal J.W., O’Neil T.E., David A., Strom G. and Andrew M.E. (1999). Cytokine therapy: a natural alternative for disease control. Vet. Immunol. Immunopathol. 72, 183-188.

Masihi K. (2002). Immunomodulators in infectious diseases: Panoply of possibilities. Int. Immunopharmacol. 22, 1083-1091.

Munday R., Munday J. and Munday C. (2003). Comparative effects of mono-. di-, tri-, and tetrasulfides derived from plants of the Allium family: Redox cycling in vitro and hemolytic activity and phase 2 enzyme induction in vivo. Free Radic. Biol. Med. 34, 1200-1211.

Newall C.A., Anderson L.A. and Phillipson J.D. (1996). Herbal Medicines: A Guide for Health-Care Professionals. Pharmaceutical Press, London, United Kingdom.

Nuutila A.M., Puupponen-Pimia R., Aarmi M. and Oksman-Caldentey K.M. (2003). Comparison of antioxidant activities of onion and garlic extracts by inhibition of lipid peroxidation and radical scavenging activity. Food Chem. 81, 485-493.

Okamura M., Lillehoj H., Raybourne R., Baru U. and Hechert R. (2004). Cell-mediated immune responses to a killed Salmonella enteritidis vaccine: Lymphocyte proliferation, T-cell changes and interleukin-6 (IL-6), IL-1, IL-2, and IFN-g production. Comp. Immunol. Microbiol. Infect. Dis. 27, 255-572.

Olukosi O.A. and Dono N.D. (2014). Modification of digesta pH and intestinal morphology with the use of benzoic acid or phytobiotics and the effects on broiler chicken growth performance and energy and nutrient utilization. J. Anim. Sci. 92, 3945-3953.

Petrolli T.G., Albino L.F.T., Rostagno H.S., Gomes P.C., Tavernari F.C. and Balbino E.M. (2012). Herbal extract in diets for broilers. Rev. Brasileira Zootec. 41(7), 1683-1690.

Pourali M., Mirghelenj S.A. and Kermanshahi H. (2010). Effects of garlic powder on productive performance and immune response of broiler chickens challenged with Newcastle disease virus. Glob. Vet. 4, 616-621.

Pryor W. (1991). The antioxidant nutrients and disease prevention-what, do we know and what, do we need to find out? Am. J. Clin. Nutr. 53(1), 391-393.

Puvača N., Kostadinović L., Ljubojević D., Lukač D., Lević J., Popović S., Novakov N., Vidović B. and Đuragić O. (2015). Effect of garlic, black pepper and hot red pepper on productive performances and blood lipid profile of broiler chickens. Europian Poult. Sci. 79, 1-13.

Qureshi A.A., Abuimeileh N., Din Z.Z., Elson C.E. and Burger W.C. (1983a). Inhibition of cholesterol and fatty acid biosynthesis in liver enzymes and chicken hepatocytes by polar fractions of garlic. Lipids. 18, 343-348.

Qureshi A.A., Din Z.Z., Abuirmeileh N., Burger W.C., Ahmad Y. and Elson C.E. (1983b). Suppression of avian hepatic lipid metabolism by solvent extracts of garlic: Impact on serum lipids. J. Nutr. 113, 1746-1755.

Rae H. (1999). Onion toxicosis in a herd of beef cows. Canadian Vet. J. 40, 55-57.

Raeesi M., Hoseini-Aliabad S.A., Roofchaee A., Zare Shahneh A. and Pirali S. (2010). Effect of periodically use of Garlic (Allium sativum) powder on performance and carcass characteristics in broiler chickens. World Acad. Sci. Eng. Technol. 4, 8-21.

Rahimi S., Teymouri Zadeh Z., Karimi Torshizi M.A., Omidbaigi R. and Rokni H. (2011). Effect of the three herbal extracts on growth performance, immune system, blood factors and intestinal selected bacterial population in broiler chickens. J. Agric. Sci. Technol. 13, 527-539.

Reddy R.V., Lightsey S.F. and Maurice D.V. (1991). Effect of feeding garlic oil on performance and egg yolk cholesterol concentration. Poult. Sci. 70, 2006-2009.

Rybak M.E., Calvet E.M. and Harnly J.M. (2004). Quantitative determination of Allicin in Garlic: Supercritical fluid extraction and standard addition of Alliin. J. Agric. Food Chem. 52, 682-687.

Sallam K.I., Ishioroshi M. and Samejima K. (2004). Antioxidant and antimicrobial effect of garlic in chicken sausage. Lebensm. Wiss. Technol. 37, 849-855.

Sampedro M., Artola R., Murature M., Murature D., Ditamo Y. and Roth G. (2004). Mannan from Aloe saponaria inhibits tumoral cell activation and proliferation. Int. Immunopharmacol. 4, 411-418.

Sarica S., Ciftci A., Demir E., Kilinc K. and Yildirim Y. (2005).Use of an antibiotic growth promoter and two herbal natural feed additives with and without exogenous enzymes in wheat based broiler diets. South African J. Anim. Sci. 35, 61-72.

Shams Shargh M., Dastar B., Zerehdaran S., Khomeiri M. and Moradi M. (2012). Effects of using plant extracts and a probiotic on performance, intestinal morphology, and microflora population in broilers. J. Appl. Poult. Res. 21, 201-208.

Sharma R.K., Singh R.A., Pal R.N. and Aggarwal C.K. (1979). Cholesterol contents of chicken eggs as affected by feeding garlic, sarpagandha and nicotinic acid. Haryana Agric. Univ. J. Res. 9, 263-265.

Shi X.H., Li S.Z., Liu Z.P., Shi X.H., Li S.Z. and Liu Z.P. (1999). Atrial on the use of garlic as a feed additive for meat chickens. Poult. Husb. Dis. Control. 10, 19-20.

Shoetan A., Augusti K.T. and Joseph P.K. (1984). Hypolipidemic effects of garlic oil in rats fed ethanol and a high lipid diet. Experimental. 40, 261-263.

Silagy C. and Neil A. (1994). Garlic as a lipid-lowering agent. Pp. 39-45 in A Meta-Analysis, J.R. Coll, Ed. Physicians, London, United Kingdom.

Sivam G.P. (2001). Protection against Helicobacter pylori and other bacterial infections by garlic. J. Nutr. 131, 1106-1108.

Stevens H. (1984). Suspected wild garlic poisoning in sheep. Vet. Record. 115, 363-371.

Szigeti G., Pálfi V., Nagy B., Iné É., Nagy G., Szmolény G., Bagó G. and Radványi S. (1998). New type of immune stimulant to increase antibody production generated by viral and bacterial vaccines. Mag. Allatorv. Lap. 120, 719-721.

Toghyani M., Toghyani M. and Gheisari A. (2011). Evaluation of cinnamon and garlic as antibiotic growth promoter substitutions on performance, immune responses, serum biochemical and haematological parameters in broiler chicks. Livest. Sci. 138, 167-173.

Van Der Kolk J. (2000). Onion poisoning in a herd of dairy cattle. Vet. Record. 147, 517-518.

Varmaghany S., Torshizi M.A.K., Rahimi S., Lotfollahian H. and Hassanzadeh M. (2015). The effects of increasing levels of dietary garlic bulb on growth performance, systolic blood pressure, hematology, and ascites syndrome in broiler chickens. Poult. Sci. 94, 1812-1820.

Warshafsky S., Kamer R.S. and Sivak S.L. (1993). Effect of garlic on total serum cholesterol. A meta-analysis. Ann. Int. Med. 119, 599-605.

Windisch W., Schedle K., Plitzner C. and Kroismayr A. (2008). Use of phytogenic products as feed additives for swine and poultry. J. Anim. Sci. 86, 140-148.

Wu C., Gan J., Jin Q., Chen C., Liang P., Wu Y., Liu X., Ma L. and Davison F. (2008). Revaccination with Marek’s disease vaccines induces productive infection and superior immunity. Clin. Vaccine Immunol. 16, 184-193.

Yalcin S., Onbaşilar Ĺ., Reisli Z. and Yalcin S. (2006). Effects of garlic powder on the performance, egg traits and blood parameters of laying hens. J. Sci. Food Agric. 86, 1336-1339.

Yalcin S., Onbaşilar Ĺ., Şehu A. and Yalcin S. (2007). The effects of dietary garlic powder on the performance, egg traits and blood serum cholesterol of laying quails. Asian-Australasian J. Anim. Sci. 20, 944-947.

Yang Y., Iji P.A. and Choct M. (2009). Dietary modulation of gut microflora in broiler chickens: A review of the role of six kinds of alternatives to in-feed antibiotics. Worlds Poult. Sci. J. 65, 97-114.

Zekić V., Puvača N., Milić D., Beuković M., Glamočić D., Vukelić N., Lukač D. and Zekić S. (2014). Effect of garlic powder in broiler chicken nutrition: Emphasis on production economic efficiency costs and chicken meat quality. Custos e Agronegocio. 10, 2-10.