Some alternatives to mitigate heat stress in animals: arginine and methionine as antioxidants

  • Reyna L. Camacho Instituto de Ciencias Agrícolas, Universidad Autónoma de Baja California
  • Ernesto Avelar Lozano Instituto de Ciencias Agrícolas, Universidad Autónoma de Baja California
  • Adriana Morales Trejo Instituto de Ciencias Agrícolas, Universidad Autónoma de Baja California
  • B. Pérez Instituto de Ciencias Agrícolas, Universidad Autónoma de Baja California
  • V. Sánchez Instituto de Ciencias Agrícolas, Universidad Autónoma de Baja California
  • Nestor Arce-Vazquez Instituto de Ciencias Agrícolas, Universidad Autónoma de Baja California
  • Miguel Cervantes Ramirez Instituto de Ciencias Agrícolas, Universidad Autónoma de Baja California
Keywords: heat stress, antioxidant enzymes, intestinal epithelium


Exposure of animals to ambient temperature above the thermo neutral zone caused heat stress. Alterations in digestion and absorption of nutrients as well as damage to the small intestine epithelia associated with the production of reactive oxygen species (ROS) may occur in heat stress pigs, resulting in depressed performance. The cells possess an antioxidant system capable of protecting the animals against the effect of heat stress. However, when ambient temperature increases beyond the thermo neutral zone, ROS production also increases provoking an imbalance between ROS and antioxidant production. This review provides relevant information related to the alterations that occur at intestinal, cellular and molecular level in animals exposed to heat stress, and the effect that methionine and arginine as antioxidant amino acids, and their use in diets for heat stress pigs.


Download data is not yet available.


Agarwal, A., and Prabakaran, S. (2005). Mechanism, measurement, and prevention of oxidative stress in male reproductive physiology. Indian Journal of Experimental Biology, 43, 963-974.
Alarcón, A., Gamboa, J., y Janacua, H. (2007). El papel de las hormonas en el estrés porcino. Tecnociencia Chihuahua, 1(2), 72-80.
Álvarez, A. (2014). El cambio climático y la producción animal. Revista Cubana de Ciencia Agrícola, 48, 7-10.
Archana, P., Aleena, J., Pragna, P., Vidia, M., Abdul, P., Bagath, M., Krishnan, G., Manimaran, A., Beena, V., Kurien, E., Sejian, V., and Bhatta, R. (2017). Role of heat shock proteins in livestock adaptation to heat stress. Journal of Dairy, Veterinary & Animal Research, 5(1), 1-8. 00127
Bachhawat, A., Thakur, A., Kaur, J., and Zulkifli, M. (2013). Glutathione transporters. Biochimica et Biophysica Acta, 1830(5), 3154-3164. gen.2012.11.018
Balasaheb, S., and Pal, D. (2015). Free radicals, natural antioxidants, and their reaction mechanisms. RSC Advances, 5(35), 27986-28006. 13315C
Bauchart-Thevret, C., Stoll, B., and Burrin, D. (2009). Intestinal metabolism of sulfur amino acids. Nutrition Research Reviews, 22(2), 175-187. 422409990138
Bauchart-Thevret, C., Stoll, B., Chacko, S., and Burrin, D. (2009). Sulfur amino acid deficiency upregulates intestinal methionine cycle activity and suppresses epithelial growth in neonatal pigs. American Journal of Physiology-Endocrinology and Metabolism, 296(6), 1239-1250.
Benítez, D. (2006). Vitaminas y oxidorreductasas antioxidantes: Defensa ante el estrés oxidativo. Revista Cubana de Investigaciones Biomédicas, 25(2), 1-8.
Bin, P., Huang, R., and Zhou, X. (2017). Oxidation resistance of the sulfur amino acids methionine and cysteine. BioMed Research International, 2017, 1-6.
Błaszczyk, A., Augustyniak, A., and Skolimowski, J. (2013). Ethoxyquin: An antioxidant used in animal feed. International Journal of Food Science, 2013, 1-12.
Bresciani, G., Manica da Cruz, I., and González, J. (2015). Manganese superoxide dismutase and oxidative stress modulation (Vol. 68, pp. 87-130). Elsevier.
Castro, F. L. D. S., & Kim, W. K. (2020). Secondary functions of arginine and sulfur amino acids in poultry health. Animals, 10(11), 2106.
Cervantes, R., y Cordova, A. (2018). Efectos metabólicos y molecular del estrés calórico en el ganado. Sociedades Rurales, Producción y Medio Ambiente, 18, 139-156.
Céspedes, E., Hernández, I., y Llópiz, N. (1996). Enzimas que participan como barreras fisiológicas para eliminar los radicales libres: II. Catalasa. Revista Cubana de Investigaciones Biomédicas, 15(2), 1-3.
Cisneros, E., Balboa, J., y Miranda, E. (1997). Enzimas que participan como barreras fisiológicas para eliminar los radicales libres: III. Glutatión peroxidasa. Revista Cubana de Investigaciones Biomédicas, 16(1), 10-15.
Cottrell, J., Liu, F., Hung, A., DiGiacomo, K., Chauhan, S., Leury, B., Furness, J., Celi, P., and Dunshea, F. (2015). Nutritional strategies to alleviate heat stress in pigs. Animal Production Science, 55(12), 1391-1402.
Dai ZL, Li XL, Xi PB, Zhang J, Wu G, Zhu WY (2012) Regulatory role for L-arginine in the utilization of amino acids by pig small-intestinal bacteria. Amino Acids 43: 233-244.
Das, R., Sailo, L., Verma, N., Bharti, P., Saikia, J., Imtiwati, and Kumar, R. (2016). Impact of heat stress on health and performance of dairy animals: A review. Veterinary World, 9(3), 260-268.
Díaz, A. (2003). La estructura de las catalasas. REB, 22, 76-84.
Downing, E., and Miyan, J. (2000). Neural immunoregulation: Emerging roles for nerves in immune homeostasis and disease. Immunology Today, 21(6), 281-289.
Duan, X., Li, F., Mou, S., Feng, J., Liu, P., & Xu, L. (2015). Effects of dietary L-arginine on laying performance and anti-oxidant capacity of broiler breeder hens, eggs, and offspring during the late laying period. Poultry science, 94(12), 2938-2943.
Elwert, C., Fernandes, E., and Lemme, A. (2008). Biological effectiveness of methionine hydroxy-analogue calcium salt in relation to DL-methionine in broiler chickens. Asian-Australasian Journal of Animal Sciences, 21(10), 1506-1515.
England, K., O’Driscoll, C., and Cotter, T. (2004). Carbonylation of glycolytic proteins is a key response to drug-induced oxidative stress and apoptosis. Cell Death and Differentiation, 11(3), 252-260.
Freeman, M., Spitz, D., and Meredith, M. (1990). Does heat shock enhance oxidative stress? Studies with ferrous and ferric iron. Radiation Research, 124(3), 288-293.
Freitas, I., Boncompagni, E., Tarantola, E., Gruppi, C., Bertone, V., Ferrigno, A., Milanesi, G., Vaccarone, R., Tira, M. E., and Vairetti, M. (2016). In situ evaluation of oxidative stress in rat fatty llver induced by a methionine- and holine-deficient diet. Oxidative Medicine and Cellular Longevity, 2016, 1-14.
Ganaie, A., Ghasura, R., Mir, N., Bumla, N., Sankar, G., and Wani, S. (2013). Biochemical and physiological changes during thermal stress in bovines: A review. Iranian Journal of Applied Animal Science, 3(3), 423-430.
García, A. (2002). El envejecimiento y el estrés oxidativo. Revista Cubana de Investigaciones Biomédicas, 21(3), 178-185.
Gómez, L. E., & Cuevas, D. B. (2008). Superóxido dismutasa. Konigsberg, M.(ed).
Guccione, E., & Richard, S. (2019). The regulation, functions and clinical relevance of arginine methylation. Nature reviews Molecular cell biology, 20(10), 642-657.
Gupta, M., Kumar, S., Dangi, S. S., and Jangir, B. L. (2013). Physiological, Biochemical and Molecular Responses to Thermal Stress in Goats -. ijlr.20130502081121
Harparkash, K., and Barry, H. (1994). Evidence for nitric oxide-mediated oxidative damage in chronic inflammation Nitrotyrosine in serum and synovial fluid from rheumatoid patients. FEBS Letters, 350(1), 9-12.
Horowitz, M., and Robinson, S. (2007). Heat shock proteins and the heat shock response during hyperthermia and its modulation by altered physiological conditions. Progress in Brain Research, 162, 433-446.
Huang, L., Yin, P., Liu, F., Liu, Y., Liu, Y., & Xia, Z. (2020). Protective effects of L‐arginine on the intestinal epithelial barrier under heat stress conditions in rats and IEC‐6 cell line. Journal of animal physiology and animal nutrition, 104(1), 385-396.
Huynh, T., Aarnink, A., Verstegen, M., Gerrits, W., Heetkamp, M., Kemp, B., and Canh, T. (2005). Effects of increasing temperatures on physiological changes in pigs at different relative humidities. Journal of Animal Science, 83(6), 1385-1396.
Key, N., & Sneeringer, S. (2014). Potential effects of climate change on the productivity of US dairies. American Journal of Agricultural Economics, 96(4), 1136-1156.
Kino, K., and Okumura, J. (1986). The effect of single essential amino acid deprivation on chick growth and nitrogen and energy balances at ad libitum- and equalized-food intakes. Poultry Science, 65(9), 1728-1735.
Kirkman, H., Galiano, S., and Gaetani, G. (1987). The function of catalase-bound NADPH. Journal of Biological Chemistry, 262(2), 660-666.
Kumar, A., Singh, G., Kumar, B., and Meur, S. (2011). Modulation of antioxidant status and lipid peroxidation in erythrocyte by dietary supplementation during heat stress in buffaloes. Livestock Science, 138(1), 299-303. 10.12.021
Kumar, Y., Yadav, D., Ahmad, T., and Narsaiah, K. (2015). Recent trends in the use of natural antioxidants for meat and meat products. Comprehensive Reviews in Food Science and Food Safety, 14(6), 796-812.
LeDoux, S., Driggers, W., Hollensworth, B., and Wilson, G. (1999). Repair of alkylation and oxidative damage in mitochondrial DNA. Mutation Research, 434(3), 149-159.
Lei, X., Zhu, J., Cheng, W., Bao, Y., Ho, Y., Reddi, A., Holmgren, A., and Arnér, E. (2016). Paradoxical roles of antioxidant enzymes: Basic mechanisms and health implications. Physiological Reviews, 96(1), 307-364. rev.00010.2014
Li, H., Wan, H., Mercier, Y., Zhang, X., Wu, C., Wu, X., Tang, L., Che, L., Lin, Y., Xu, S., Tian, G., Wu, D., and Fang, Z. (2014). Changes in plasma amino acid profiles, growth performance and intestinal antioxidant capacity of piglets following increased consumption of methionine as its hydroxy analogue. British Journal of Nutrition, 112(6), 855-867.
Lian, P., Braber, S., Garssen, J., Wichers, H., Folkerts, G., Fink-Gremmels, J., and Varasteh, S. (2020). Beyond heat stress: Intestinal integrity disruption and mechanism-based intervention strategies. Nutrients, 12(3), 734. 3390/nu12030734
Liu, F., Yin, J., Du, M., Yan, P., Xu, J., Zhu, X., and Yu, J. (2009). Heat-stress-induced damage to porcine small intestinal epithelium associated with downregulation of epithelial growth factor signaling. Journal of Animal Science, 87(6), 1941-1949.
Liu, G., Zong, K., Zhang, L., and Cao, S. (2010). Dietary methionine affect meat qulity and myostatin gene exon 1 region methylation in skeletal muscle tissues of broilers. Agricultural Sciences in China, 9(9), 1338-1346.
Liochev, S. I., & Fridovich, I. (1999). Superoxide and iron: partners in crime. IUBMB life, 48(2), 157-161.
Lu, T., Piao, X., Zhang, Q., Wang, D., Piao, X., and Kim, S. (2010). Protective effects of forsythia suspensa extract against oxidative stress induced by diquat in rats. Food and Chemical Toxicology, 48(2), 764-770.
Manno, M., Oliveira, R., Donzele, J., Oliveira, W., Vaz, R., Silva, B., Saraiva, E., and Souza, K. (2006). Efeitos da temperatura ambiente sobre o desempenho de suínos dos 30 aos 60 kg. Revista Brasileira de Zootecnia, 35(2), 471-477. 10.1590/S1516-35982006000200019
Manteca, X. (2012). Bienestar animal. _line/51-manual_porcino/08-BuenasPracticasCap8.pdf
Marin, A. L. M. (2006). Efectos climáticos sobre la producción del vacuno lechero: estrés por calor. REDVET. Revista Electrónica de Veterinaria, 7(10), 1-22.
Martínez, Y., Li, X., Liu, G., Bin, P., Yan, W., Más, D., Valdivié, M., Hu, C., Ren, W., and Yin, Y. (2017). The role of methionine on metabolism, oxidative stress, and diseases. Amino Acids, 49(12), 2091-2098. 94-2
Mehta, S., and Gowder, S. (2015). Members of antioxidant machinery and their functions. Basic Principles and Clinical Significance of Oxidative Stress, 14, 59-85.
Morales, A., Chávez, M., Vásquez, N., Camacho, L., Avelar, E., Arce, N., Htoo, J. K., and Cervantes, M. (2019). Extra dietary protein-bound or free amino acids differently affect the serum concentrations of free amino acids in heat-stressed pigs. Journal of Animal Science, 97(4), 1734-1744.
Morales, A., Grageola, F., García, H., Arce, N., Araiza, B., Yáñez, J., and Cervantes, M. (2014). Performance serum amino acid concentrations and expression of selected genes in pair-fed growing pigs exposed to high ambient temperatures. Journal of Animal Physiology and Animal Nutrition, 98(5), 928-935. jpn.12161
Morales, A., Hernández, L., Buenabad, L., Avelar, E., Bernal, H., Baumgard, L., and Cervantes, M. (2016). Effect of heat stress on the endogenous intestinal loss of amino acids in growing pigs. Journal of Animal Science, 94(1), 165-172.
Morales, A., González, F., Bernal, H., Camacho, R. L., Arce, N., Vásquez, N., ... & Cervantes, M. (2021). Effect of arginine supplementation on the morphology and function of intestinal epithelia and serum concentrations of amino acids in pigs exposed to heat stress. Journal of Animal Science, 99(9), skab179.
Mujahid, A., Akiba, Y., and Toyomizu, M. (2007). Acute heat stress induces oxidative stress and decreases adaptation in young white leghorn cockerels by downregulation of avian uncoupling protein. Poultry Science, 86(2), 364-371. ps/86.2.364
Mujahid, A., Pumford, N. R., Bottje, W., Nakagawa, K., Miyazawa, T., Akiba, Y., and Toyomizu, M. (2007). Mitochondrial oxidative damage in chicken skeletal muscle induced by acute heat stress. Poultry Science, 44(439-445).
Nisar, N., Sultana, M., Waiz, H., Para, P., and Dar, S. (2013). Oxidative stress—Threat to animal health and production. International Journal of Livestock Research, 3(2), 76-83.
Ooue, A., Ichinose-Kuwahara, T., Shamsuddin, A., Inoue, Y., Nishiyasu, T., Koga, S., and Kondo, N. (2007). Changes in blood flow in a conduit artery and superficial vein of the upper arm during passive heating in humans. European Journal of Applied Physiology, 101(1), 97-103.
Pearce, S., Sanz, M., Hollis, J., Baumgard, L., and Gabler, N. (2014). Short-term exposure to heat stress attenuates appetite and intestinal integrity in growing pigs. Journal of Animal Science, 92(12), 5444-5454.
Pollmann, D. S. (2010). Seasonal effects on sow herds: industry experience and management strategies. J. Anim. Sci, 88(Suppl 3), 9.
Roca, A. (2011). Efectos del estres calorico en el bienestar animal, una revision en tiempo de cambio climatico. ESPAMCIENCIA, 2(1), 15-25.
Rubbo, H., Radi, R., Trujillo, M., Telleri, R., Kalyanaraman, B., Barnes, S., Kirk, M., and Freeman, B. (1994). Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. Journal of Biological Chemistry, 269(42), 26066-26075.
Salami, S., Guinguina, A., Agboola, J., Omede, A., Agbonlahor, E., and Tayyab, U. (2016). In vivo and postmortem effects of feed antioxidants in livestock: A review of the implications on authorization of antioxidant feed additives. Animal, 10(8), 1375-1390.
Sarrasague, M., Barrado, D., Zubillaga, M., Hager, A., Paoli, T., and Boccio, J. (2006). Conceptos actuales del metabolismo del glutatión. 11.
Schindeldecker, M., and Moosmann, B. (2015). Protein-borne methionine residues as structural antioxidants in mitochondria. Amino Acids, 47(7), 1421-1432.
Segal, A., and Abo, A. (1993). The biochemical basis of the NADPH oxidase of the phagocytes. Trends in Biochemical Sciences, 18(2), 43-47. 1016/0968-0004(93)90051-N
Servicio Meteorologico Nacional Argentino. (s/f). Servicio Meteorologico Nacional. Recuperado el 25 de enero de 2022, de
Sies, H. (1999). Glutathione and its role in cellular functions. Free Radical Biology and Medicine, 27(9-10), 916-921.
Slimen, I., Najar, T., Ghram, A., and Abdrrabba, M. (2016). Heat stress effects on livestock: Molecular, cellular and metabolic aspects, a review. Journal of Animal Physiology and Animal Nutrition, 100(3), 401-412. jpn.12379
Stadtman, E., and Levine, R. (2000). Protein Oxidation. Annals of the New York Academy of Sciences, 899(1), 191-208.
Stuehr, D. J. (2004). Enzymes of the L-arginine to nitric oxide pathway. The Journal of nutrition, 134(10), 2748S-2751S.
St-Pierre, N., Cobanov, B., and Schnitkey, G. (2003). Economic losses from heat stress by US livestock industries. Journal of Dairy Science, 86, 52-77. 10.3168/jds.S0022-0302(03)74040-5
Takahashi, K., and Cohen, H. (1986). Selenium-dependent glutathione peroxidase protein and activity: Immunological investigations on cellular and plasma enzymes. Blood, 68(3), 640-645.
Temple, D., Bargo, F., Mainau, E., Ipharraguerre, I., y Manteca, X. (2015). Efecto del estrés por calor en la producción de vacas de leche. FARM ANIMAL WELFARE EDUCATION CENTRE, 8, 1-2.
Tobón, E., Pastrana, R., Márquez, H., Matsumura, P., y Ríos, E. (2018). Papel del glutatión reducido (GSH) en el proceso de capacitación espermática (pp. 136-152).
Troy, R., Bosch, M., Rick, E., Lee, B., Wagner, E., Seidlova, D., Wuttke, W., Scanlan, T., Rønnekleiv, O., and Kelly, M. (2010). Contribution of a membrane estrogen receptor to the estrogenic regulation of body temperature and energy homeostasis. Endocrinology, 151(10), 4926-4937.
Venereo, J. (2002). Daño oxidativo, radicales libres y antioxidantes. Revista Cubana de Medicina Militar, 31(2), 126-133.
Vesco, A., Gasparino, E., Grieser, O., Zancanela, V., Soares, M., and Oliveira, A. (2015). Effects of methionine supplementation on the expression of oxidative stress-related genes in acute heat stress-exposed broilers. British Journal of Nutrition, 113(4), 549-559.
Wang, Y., Branicky, R., Noë, A., and Hekimi, S. (2018). Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling. Journal of Cell Biology, 217(6), 1915-1928.
Wu G, Wu Z, Dai Z, Yang Y, Wang W, Liu C, et al. (2013) Dietary requirements of “nutritionally non-essential amino acids” by animals and humans. Amino Acids 44: 1107-1113.
Wu, L. (2015). Effects of reducing dietary protein on the expression of nutrition sensing genes (amino acid transporters) in weaned piglets. Journal of Zhejiang University-SCIENCE B, 16(6), 496–502.
Yi, H., Xiong, Y., Wu, Q., Wang, M., Liu, S., Jiang, Z., & Wang, L. (2020). Effects of dietary supplementation with l‐arginine on the intestinal barrier function in finishing pigs with heat stress. Journal of animal physiology and animal nutrition, 104(4), 1134-1143.
Yin, J., Ren, W., Chen, S., Li, Y., Han, H., Gao, J., Liu, G., Wu, X., Li, T., Kim, W., and Yin, Y. (2018). Metabolic regulation of methionine restriction in diabetes. Molecular Nutrition and Food Research, 62(10), 1-9.
Yoon, S. Y., Sa, S., Cho, E. S., Ko, H., Kim, G. W., Choi, J. W., & Kim, J. (2020). Dietary ZnO and arginine supplementation on the dynamic change of microbiota, intestinal morphology, and immune function of weaned pigs subjected to heat stress. Research Square. Preprint. 0.21203/
Young, I., and Woodside, J. (2001). Antioxidants in health and disease. Journal of Clinical Pathology, 54(3), 176-186.
Yu, J., Yin, P., Liu, F., Cheng, G., Guo, K., Lu, A., Zhu, X., Luan, W., and Xu, J. (2010). Effect of heat stress on the porcine small intestine: A morphological and gene expression study. Comparative Biochemistry and Physiology, 156(1), 119-128.
Zachara, B. (1992). Mammalian selenoproteins. Journal of Trace Elements and Electrolytes in Health and Disease, 6(3), 137-151.
Zeitz, J., Kaltenböck, S., Most, E., and Eder, K. (2017). Antioxidant status and expression of inflammatory genes in gut and liver of piglets fed different dietary methionine concentrations. Journal of Animal Physiology and Animal Nutrition, 101(6), 1166-1174.
Zeitz, J., Kaltenböck, S., Most, E., and Eder, K. (2019). Effects of L-methionine on performance, gut morphology and antioxidant status in gut and liver of piglets in relation to DL-methionine. Journal of Animal Physiology and Animal Nutrition, 103(1), 242-250.
Zhang, H., Li, Y., Chen, Y., Ying, Z., Su, W., Zhang, T., Dong, Y., Htoo, J., Zhang, L., and Wang, T. (2019). Effects of dietary methionine supplementation on growth performance, intestinal morphology, antioxidant capacity and immune function in intra-uterine growth-retarded suckling piglets. Journal of Animal Physiology and Animal Nutrition, 103(3), 868-881.
Zhang, S., Saremi, B., Gilbert, E., and Wong, E. (2017). Physiological and biochemical aspects of methionine isomers and a methionine analogue in broilers. Poultry Science, 96(2), 425-439.
Zhao, Q., Fujiwara, Y., and Kondo, T. (2006). Mechanism of cell death induction by nitroxide and hyperthermia. Free Radical Biology and Medicine, 40(7), 1131-1143.
How to Cite
Camacho, Reyna L., Ernesto Avelar Lozano, Adriana Morales Trejo, B. Pérez, V. Sánchez, Nestor Arce-Vazquez, and Miguel Cervantes Ramirez. 2022. “Some Alternatives to Mitigate Heat Stress in Animals: Arginine and Methionine As Antioxidants”. Latin American Archives of Animal Production 30 (Supl. 1), 103-17.