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Molecular targets of dietary phytochemicals for the alleviation of heat stress in poultry

  • K. SAHIN (a1), C. ORHAN (a1), M.O. SMITH (a2) and N. SAHIN (a1)


Heat stress compromises performance and productivity through reducing feed intake, while decreasing nutrient utilisation, growth rate, egg production, egg quality and feed efficiency, leading to economic losses in poultry. High temperatures can lead to oxidative stress associated with a reduced antioxidant status in the bird in vivo, as reflected by increased oxidative damage and lowered plasma concentrations of antioxidants. Several strategies are currently available to alleviate the negative effects of high environmental temperature on the performance of poultry. However, as it is expensive to cool buildings in which animals are housed, many efforts are focused on dietary manipulation. In terms of reducing the negative effects of environmental stress, antioxidants are used in poultry feed because of the reported benefits of these supplements, including their anti-stress effects. In this review, the mode of action of these supplements is investigated, and evidence is presented showing that phytochemicals can alter several cell signalling pathways. The agents include epigallocatechin-3-gallate (EGCG; green tea), lycopene (tomato) and resveratrol (red grapes, peanuts and berries). The cell-signalling pathways inhibited by EGCG include transcription factors (nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)) and nuclear factors (erythroid-derived 2-like 2 (Nrf2)) and activator protein-1 (AP-1) that regulate cyclooxygenase-2 (COX-2). This review will also address some of the mechanisms proposed for the heat stress preventive activity of EGCG, lycopene and resveratrol focusing on the induction of antioxidant enzymes (phase II enzymes) through the activation of the antioxidant response element (ARE) transcription system.


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AGGARWAL, B.B. and SHISHODIA, S. (2006) Molecular targets of dietary agents for prevention and therapy of cancer. Biochemical Pharmacology 71: 1397-1421.
ALI, S. and MANN, D.A. (2004) Signal transduction via the NF-kappaB pathway: a targeted treatment modality for infection, inflammation and repair. Cell Biochemistry and Function 22: 67-79.
ANDO, M., KATAGIRI, K., YAMAMOTO, S., WAKAMATSU, K., KAWAHARA, I., ASANUMA, S., USUDA, M. and SASAKI, K. (1997) Age-related effects of heat stress on protective enzymes for peroxides and microsomal monooxygenase in rat liver. Environmental Health Perspectives 105: 726-733.
BEN-DOR, A., STEINER, M., GHEBER, L., DANILENKO, M., DUBI, N., LINNEWIEL, K., ZICK, A., SHARONI, Y. and LEVY, J. (2005) Carotenoids activate the antioxidant response element transcription system. Molecular Cancer Therapeutics 4: 177-186.
BOGIN, E., AVIDAR, Y., PECH-WAFFENSCHMIDT, V., DORON, Y., ISRAELI, B.A. and KEVHAYEV, E. (1996) The relationship between heat stress, survivability and blood composition of the domestic chicken. European Journal of Clinical Chemistry and Clinical Biochemistry 34: 463-469.
DINKOVA-KOSTOVA, A.T., HOLTZCLAW, W.D., COLE, R.N., ITOH, K., WAKABAYASHI, N., KATOH, Y., YAMAMOTO, M. and TALALAY, P. (2002) Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proceedings of the National Academy of Sciences of the United States of America 99: 11908-11913.
ETCHES, R., JOHN, J.M. and GIBBINS, A.M.V. (2008) Behavioural, physiological, neuroendocrine and molecular responses to heat stress, in: DAGHIR, N.J. (Ed.) Poultry Production in Hot Climates, Second Edition, pp. 48-79 (CAB International, Wallingford, UK).
GARG, R. and MARU, G. (2009) Dietary curcumin enhances benzo(a)pyrene-induced apoptosis resulting in a decrease in BPDE-DNA adducts in mice. Journal of Environmental Pathology, Toxicology and Oncology 28: 121-131.
GILMORE, T.D. (2006) Introduction to NF-kappaB: players, pathways, perspectives. Oncogene 25: 6680-6684.
GUPTA, S.C., SUNDARAM, C., REUTER, S. and AGGARWAL, B.B. (2010) Inhibiting NF-κB activation by small molecules as a therapeutic strategy. Biochimica et Biophysica Acta 1799: 775-787.
GUPTA, A., KUMAR, A. and KULKARNI, S.K. (2011) Targeting oxidative stress, mitochondrial dysfunction and neuroinflammatory signalling by selective cyclooxygenase (COX)-2 inhibitors mitigates MPTP-induced neurotoxicity in mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry 35: 974-981.
HARGREAVES, M., DILLO, P., ANGUS, D. and FEBBRAIO, M. (1996) Effect of fluid ingestion on muscle metabolism during prolonged exercise. Journal of Applied Physiology 80: 363-366.
ITOH, K., WAKABAYASHI, N., KATOH, Y., ISHII, T., IGARASHI, K., ENGEL, J.D. and YAMAMOTO, M. (1999) Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes and Development 13: 76-86.
IWAGAMI, Y. (1996) Changes in the ultrastructure of human cells related to certain biological responses under hyperthermic culture conditions. Human Cell 9: 353-366.
KELLOFF, G.J., CROWELL, J.A., STEELE, V.E., LUBET, R.A., MALONE, W.A., BOONE, C.W., KOPELOVICH, L., HAWK, E.T., LIEBERMAN, R., LAWRENCE, J.A., ALI, I., VINER, J.L. and SIGMAN, C.C. (2000) Progress in cancer chemoprevention: development of diet-derived chemopreventive agents. Journal of Nutrition 130: 467-471.
KOBAYASHI, A., KANG, M.I., WATAI, Y., TONG, K.I., SHIBATA, T., UCHIDA, K. and YAMAMOTO, M. (2006) Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of Keap1. Molecular and Cellular Biology 26: 221-229.
LI, H.Y., ZHONG, Y.F., WU, S.Y. and SHI, N. (2007) NF-E2 related factor 2 activation and heme oxygenase-1 induction by tert-butylhydroquinone protect against deltamethrin-mediated oxidative stress in PC12 cells. Chemical Research in Toxicology 20: 1242-1251.
LIAN, F. and WANG, X.D. (2008) Enzymatic metabolites of lycopene induce Nrf2-mediated expression of phase II detoxifying/antioxidant enzymes in human bronchial epithelial cells. International Journal of Cancer 123: 1262-1268.
MAGER, W.H. and De KRUIJFF, A.J. (1995) Stress-induced transcriptional activation. Microbiological Reviews 59: 506-531.
MANNA, S.K., MUKHOPADHYAY, A. and AGGARWAL, B.B. (2000) Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. The Journal of Immunology 164: 6509-6519.
MASHALY, M.M., HENDRICKS, G.L., KALAMA, M.A., GEHAD, A.E., ABBAS, A.O. and PATTERSON, P.H. (2004) Effect of heat stress on production parameters and immune responses of commercial laying hens. Poultry Science 83: 889-894.
MUJAHID, A., YOSHIKI, Y., AKIBA, Y. and TOYOMIZU, M. (2005) Superoxide radical production in chicken skeletal muscle induced by acute heat stress. Poultry Science 84: 307-314.
MUKHTAR, H. and AHMAD, N. (2000) Tea polyphenols: prevention of cancer and optimizing health. The American Journal of Clinical Nutrition 71: 1698-1704.
NA, H.K. and SURH, Y.J. (2008) Modulation of Nrf2-mediated antioxidant and detoxifying enzyme induction by the green tea polyphenol EGCG. Food and Chemical Toxicology 46: 1271-1278.
NAIR, S., BARVE, A., KHOR, T.O., SHEN, G.X., LIN, W., CHAN, J.Y., CAI, L. and KONG, A.N. (2010) Regulation of Nrf2- and AP-1-mediated gene expression by epigallocatechin-3-gallate and sulforaphane in prostate of Nrf2-knockout or C57BL/6J mice and PC-3 AP-1 human prostate cancer cells. Acta Pharmacologica Sinica 31: 1223-1240.
NAIR, S., LI, W. and KONG, A.N. (2007) Natural dietary anti-cancer chemopreventive compounds: redox-mediated differential signalling mechanisms in cytoprotection of normal cells versus cytotoxicity in tumour cells. Acta Pharmacologica Sinica 28: 459-472.
NELSON, D.E., IHEKWABA, A.E., ELLIOTT, M., JOHNSON, J.R., GIBNEY, C.A., FOREMAN, B.E., NELSON, G., SEE, V., HORTON, C.A., SPILLER, D.G., EDWARDS, S.W., MCDOWELL, HP., UNITT, J.F., SULLIVAN, E., GRIMLEY, R., BENSON, N., BROOMHEAD, D., KELL, D.B. and WHITE, M.R. (2004) Oscillations in NF-kappaB signalling control the dynamics of gene expression. Science 306: 704-708.
NGUYEN, T., NIOI, P. and PICKETT, C.B. (2009) The Nrf2-antioxidant response element signalling pathway and its activation by oxidative stress. The Journal of Biological Chemistry 284: 13291-13295.
ORHAN, C., TUZCU, M., GENCOGLU, H., SAHIN, N. and SAHIN, K. (2012) Epigallocatechin-3-gallate inhibits activation of AP-1, COX-2 and heat shock proteins in liver of quail reared under heat stress (Unpublished).
SAHIN, K., ORHAN, C., AKDEMIR, F., TUZCU, M., IBEN, C. and SAHIN, N. (2012) Resveratrol protects quail hepatocytes against heat stress: modulation of the Nrf2 transcription factor and heat shock proteins. Journal of Animal Physiology and Animal Nutrition 96: 66-74.
SAHIN, K., ORHAN, C., TUZCU, M., ALI, S., SAHIN, N. and HAYIRLI, A. (2010) Epigallocatechin-3-gallate prevents lipid peroxidation and enhances antioxidant defense system via modulating hepatic nuclear transcription factors in heat-stressed quails. Poultry Science 89: 2251-2258.
SAHIN, K., SAHIN, N., KUCUK, O., HAYIRLI, A. and PRASAD, A.S. (2009a) Role of dietary zinc in heat-stressed poultry: a review. Poultry Science 88: 2176-2183.
SAHIN, N., ORHAN, C., TUZCU, M., SAHIN, K. and KUCUK, O. (2008) The effects of tomato powder supplementation on performance and lipid peroxidation in quail. Poultry Science 87: 276-283.
SAHIN, N., TUZCU, M., ORHAN, C., ONDERCI, M., EROKSUZ, Y. and SAHIN, K. (2009b) The effects of vitamin C and E supplementation on heat shock protein 70 response of ovary and brain in heat-stressed quail. British Poultry Science 50: 259-265.
SAHIN, K. and KUCUK, O. (2003) Heat stress and dietary vitamin supplementation of poultry diets. Nutrition Abstracts and Reviews. Series B: Livestock Feeds and Feeding 73: 41-50.
SAHIN, K., ORHAN, C., AKDEMIR, F., TUZCU, T., ALI, S. and SAHIN, N. (2011) Tomato powder supplementation activates Nrf-2 via ERK/Akt signalling pathway and attenuates heat stress-related responses in quails. Animal Feed Science and Technology 65: 230-237.
SANDERCOCK, D.A., HUNTER, R.R., NUTE, G.R., MITCHELL, M.A. and HOCKING, P.M. (2001) Acute heat stress-induced alterations in blood acid-base status and skeletal muscle membrane integrity in broiler chickens at two ages: implications for meat quality. Poultry Science 80: 418-425.
SEN, R. and BALTIMORE, D. (1986) Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell 47: 921-928.
SHAULIAN, E. and KARIN, M. (2002) AP-1 as a regulator of cell life and death. Nature Cell Biology 4: 131-136.
SHEN, G., XU, C., HU, R., JAIN, M.R., GOPALKRISHNAN, A., NAIR, S., HUANG, M.T., CHAN, J.Y. and KONG, A.N. (2006) Modulation of nuclear factor E2-related factor 2-mediated gene expression in mice liver and small intestine by cancer chemopreventive agent curcumin. Molecular Cancer Therapeutics 5: 39-51.
SIEGEL, H.S. (1995) Stress, Strains and Resistance. British Poultry Science 36: 3-22.
SINGH, S. and AGGARWAL, B.B. (1995) Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. The Journal of Biological Chemistry 270: 24995-25000.
SMITH, A.J. (1974) Changes in the average weight and shell thickness of eggs produced by hens exposed to high environmental temperatures. A review. Tropical Animal Health and Production 6: 237-244.
SUBBARAMAIAH, K., CHUNG, W.J., MICHALUART, P., TELANG, N., TANABE, T., INOUE, H., JANG, M., PEZZUTO, J.M. and DANNENBERG, A.J. (1998) Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. The Journal of Biological Chemistry 273: 21875-21882.
SURH, Y.J. and NA, H.K. (2008) NF-kappaB and Nrf2 as prime molecular targets for chemoprevention and cytoprotection with anti-inflammatory and antioxidant phytochemicals. Genes and Nutrition 2: 313-317.
THAXTON, P. and SIEGEL, H.S. (1970) Immunodepression in young chickens by high environmental temperature. Poultry Science 49: 202-205.
TREVISANATO, S.I. and KIM, Y.I. (2000) Tea and health. Nutrition Reviews 58: 1-10.
TUZCU, M., SAHIN, N., KARATEPE, M., CIKIM, G., KILINC, U. and SAHIN, K. (2008) Epigallocatechin-3-gallate supplementation can improve antioxidant status in stressed quail. British Poultry Science 49: 643-648.
WILLIAMS, C.S., MANN, M. and DUBOIS, R.N. (1999) The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 18: 7908-7916.
WOLFENSON, D., FERI, Y.F., SNAPIR, N. and BERMAN, A. (1979) Effect of diurnal or nocturnal heat stress on egg formation. British Poultry Science 20: 167-174.
YALCIN, S., OZKAN, , S, , TURKMUT, L. and SIEGEL, P.B. (2001) Responses to heat stress in commercial and local broiler stocks. 1. Performance traits. British Poultry Science 42: 149-152.
YAMAMOTO, T., SUZUKI, T., KOBAYASHI, A., WAKABAYASHI, J., MAHER, J., MOTOHASHI, H. and YAMAMOTO, M. (2008) Physiological significance of reactive cysteine residues of Keap1 in determining Nrf2 activity. Molecular and Cellular Biology 28: 2758-2770.
YANG, F., OZ, H.S., BARVE, S., DE VILLIERS, W.J., MCCLAIN, C.J. and VARILEK, G.W. (2001) The green tea polyphenol ( )-epigallocatechin-3-gallate blocks nuclear factor-kappa B activation by inhibiting I kappa B kinase activity in the intestinal epithelial cell line IEC-6. Molecular Pharmacology 60: 528-533.
YU, R., CHEN, C., MO, Y.Y., HEBBAR, V., OWUOR, E.D., TAN, T.H. and KONG, A.N. (2000) Activation of mitogen-activated protein kinase pathways induces antioxidant response element-mediated gene expression via a Nrf2-dependent mechanism. The Journal of Biological Chemistry 275: 39907-39913.


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Molecular targets of dietary phytochemicals for the alleviation of heat stress in poultry

  • K. SAHIN (a1), C. ORHAN (a1), M.O. SMITH (a2) and N. SAHIN (a1)


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