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Responses of growth performance and tryptophan metabolism to oxidative stress induced by diquat in weaned pigs

  • M. Lv (a1), B. Yu (a1), X. B. Mao (a1), P. Zheng (a1), J. He (a1) and D. W. Chen (a1)...


During many pathological conditions, the tryptophan concentration in blood may be reduced. However, the effects of oxidative stress on tryptophan metabolism remain unknown. In this study, we investigated the effects of oxidative stress on growth performance and tryptophan metabolism in weaned pigs. A total of 24 weaned pigs were assigned to one of three treatments that included pigs fed ad libitum (control), pigs challenged with diquat at a dose of 10 mg/kg BW and fed ad libitum (oxidative stress) or pigs pair-fed to receive the same amount of feed as the diquat-challenged pigs. The trial lasted for 7 days. The growth performance and activities of antioxidant enzymes were declined in diquat-challenged pigs. The diquat challenge decreased the tryptophan concentration in serum and the 5-hydroxytryptamine concentration in the hypothalamus, and increased large neutral amino acids, kynurenine (Kyn) and malondialdehyde in serum. The 544-bp porcine partial mRNA sequence of the tryptophan 2,3-dioxygenase (TDO) gene was obtained according to the conserved region in the human gene sequence. In addition, the oxidative stress induced by the diquat challenge stimulated TDO-relative mRNA abundance in the liver and γ-glutamyl transpeptidase activity in intestinal mucosa, but did not affect the mRNA levels of Na+-neutral amino acid transporter B0. These results suggested that oxidative stress induced by diquat depressed growth performance and increased metabolism of tryptophan via Kyn pathway that upregulated TDO mRNA expression in weaned pigs.


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Anthony, TG, Reiter, AK, Anthony, JC, Kimball, SR, Jefferson, LS 2001. Deficiency of dietary EAA preferentially inhibits mRNA translation of ribosomal proteins in liver of meal-fed rats. American Journal of Physiology – Endocrinology and Metabolism 281, E430E439.
Beckman, KB, Ames, BN 1998. The free radical theory of aging matures. Physiological Reviews 78, 547581.
Dairam, A, Antunes, E, Saravanan, K, Daya, S 2006. Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels. Life Sciences 79, 22692274.
Diksic, M, Young, SN 2001. Study of the brain serotonergic system with labeled alpha-methyl-l-tryptophan. Journal of Neurochemistry 78, 11851200.
Fernstrom, JD 2005. Branched-chain amino acids and brain function. Journal of Nutrition 135, 1539S1546S.
Freedman, DX, Belendiuk, K, Belendiuk, GW, Crayton, JW 1981. Blood tryptophan metabolism in chronic schizophrenics. Archives of General Psychiatry 38, 655659.
Fu, Y, Cheng, WH, Porres, JM, Ross, DA, Lei, XG 1999. Knockout of cellular glutathione peroxidase gene renders mice susceptible to diquat-induced oxidative stress. Free Radical Biology and Medicine 27, 605611.
Gallagher, EP, Buetler, TM, Stapleton, PL, Wang, C, Stahl, DL, Eaton, DL 1995. The effects of diquat and ciprofibrate on mRNA expression and catalytic activities of hepatic xenobiotic metabolizing and antioxidant enzymes in rat liver. Toxicology and Applied Pharmacology 134, 8191.
Gutteridge, JM 1995. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clinical Chemistry 41, 18191828.
Guzik, AC, Matthews, JO, Kerr, BJ, Bidner, TD, Southern, LL 2006. Dietary tryptophan effects on plasma and salivary cortisol and meat quality in pigs. Journal of Animal Science 84, 22512259.
Hawkins, RA, O'Kane, RL, Simpson, IA, Vina, JR 2006. Structure of the blood–brain barrier and its role in the transport of amino acids. Journal of Nutrition 136, 218S226S.
Henry, Y, Seve, B, Colleaux, Y, Ganier, P, Saligaut, C, Jego, P 1992. Interactive effects of dietary levels of tryptophan and protein on voluntary feed intake and growth performance in pigs, in relation to plasma free amino acids and hypothalamic serotonin. Journal of Animal Science 70, 18731887.
Koopmans, SJ, Guzik, AC, van der Meulen, J, Dekker, R, Kogut, J, Kerr, BJ, Southern, LL 2006. Effects of supplemental l-tryptophan on serotonin, cortisol, intestinal integrity, and behavior in weanling piglets. Journal of Animal Science 84, 963971.
Kumar, S 2004. Changes in rat brain regions serotoninergic system following acephate poisoning. Pesticide Biochemistry and Physiology 78, 140150.
Lestaevel, P, Romero, E, Dhieux, B, Ben Soussan, H, Berradi, H, Dublineau, I, Voisin, P, Gourmelon, P 2009. Different pattern of brain pro-/anti-oxidant activity between depleted and enriched uranium in chronically exposed rats. Toxicology 258, 19.
Lightfoot, T, Skibola, C, Smith, A, Forrest, M, Adamson, P, Morgan, G, Bracci, P, Roman, E, Smith, M, Holly, E 2006. Polymorphisms in the oxidative stress genes, superoxide dismutase, glutathione peroxidase and catalase and risk of non-Hodgkin's lymphoma. Haematologica 91, 12221227.
Makino, N, Mochizuki, Y, Bannai, S, Sugita, Y 1994. Kinetic studies on the removal of extracellular hydrogen peroxide by cultured fibroblasts. Journal of Biological Chemistry 269, 10201025.
Mates, JM, Sanchez-Jimenez, F 1999. Antioxidant enzymes and their implications in pathophysiologic processes. Frontiers in Bioscience 4, D339D345.
Melchior, D, Le Floc'h, N, Seve, B 2003. Effects of chronic lung inflammation on tryptophan metabolism in piglets. Advances in Experimental Medicine and Biology 527, 359362.
National Research Council (NRC) 1998. Nutrient requirement of swine, 10th edition. National Academy Press, Washington, DC, USA.
Osburn, WO, Wakabayashi, N, Misra, V, Nilles, T, Biswal, S, Trush, MA, Kensler, TW 2006. Nrf2 regulates an adaptive response protecting against oxidative damage following diquat-mediated formation of superoxide anion. Archives of Biochemistry and Biophysics 454, 715.
Palacin, M, Estevez, R, Bertran, J, Zorzano, A 1998. Molecular biology of mammalian plasma membrane amino acid transporters. Physiological Reviews 78, 9691054.
Pfaffl, MW 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research 29, e45.
Romeu, M, Mulero, M, Giralt, M, Folch, J, Nogues, MR, Torres, A, Fortuno, A, Sureda, FX, Cabre, M, Paternain, JL, Mallol, J 2002. Parameters related to oxygen free radicals in erythrocytes, plasma and epidermis of the hairless rat. Life Sciences 71, 17391749.
Schallreuter, KU, Gibbons, NC, Zothner, C, Abou Elloof, MM, Wood, JM 2007. Hydrogen peroxide-mediated oxidative stress disrupts calcium binding on calmodulin: more evidence for oxidative stress in vitiligo. Biochemical and Biophysical Research Communications 360, 7075.
Slaughter, MR, Thakkar, H, O'Brien, PJ 2002. Effect of diquat on the antioxidant system and cell growth in human neuroblastoma cells. Toxicology and Applied Pharmacology 178, 6370.
Slavic, M, Appiah, I, Nikolic-Kokic, A, Radojicic, R, Jones, DR, Spasic, MB, Milovanovic, S, Blagojevic, D 2006. The anti-oxidative defence system in the isolated rat uterus during spontaneous rhythmic activity. Acta Physiologica Hungarica 93, 335339.
Vina, JR, Palacin, M, Puertes, IR, Hernandez, R, Vina, J 1989. Role of the gamma-glutamyl cycle in the regulation of amino acid translocation. American Journal of Physiology 257, E916E922.
Wozniak, A, Drewa, G, Wozniak, B, Schachtschabel, DO 2004. Activity of antioxidant enzymes and concentration of lipid peroxidation products in selected tissues of mice of different ages, both healthy and melanoma-bearing. Zeitschrift für Gerontologie und Geriatrie 37, 184189.
Yang, CB, Wang, ZR, Yin, YL, Yang, XJ, Pluske, JR, Fan, ZM 2006. The neutral amino acid transporter B0 gene is up-regulated in the jejunal villus cells compared to crypt cells measured by quantitative real-time RT-PCR in formula-fed neonatal pigs. FASEB Journal 20, A1044.
Yuan, SB, Chen, DW, Zhang, KY, Yu, B 2007. Effects of oxidative stress on growth performance, nutrient digestibilities and activities of antioxidative enzymes of weanling pigs. Asian-Australasian Journal of Animal Sciences 20, 16001605.
Zhang, H, Forman, HJ, Choi, J 2005. Gamma-glutamyl transpeptidase in glutathione biosynthesis. Methods in Enzymology 401, 468483.



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