[Frontiers in Bioscience, Landmark, 20, 1116-1143, June 1, 2015]

Tryptophan-kynurenine pathway is dysregulated in inflammation, and immune activation

Qiongxin Wang 1 , Danxia Liu 2 , Ping Song 1 , Ming-Hui Zou 1

1Division of Molecular Medicine, Department of Medicine, and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA, 2Division of Cardiology and Endocrinology, Department of Internal Medicine, Hubei Provincial Corps Hospital, Chinese People’s Armed Police Forces, Wuhan, Hubei 430061, China


1. Abstract
2. Introduction
3. Kynurenine pathway
    3.1. Major enzymes
      3.1.1. Indoleamine-pyrrole 2, 3-dioxygenase
      3.1.2. Tryptophan 2, 3-dioxygenase
      3.1.3. Kynurenine-3-monooxygenase
      3.1.4. Kynurenine aminotransferase
      3.1.5. Kynureninase
    3.2. Major metabolites
      3.2.1. Tryptophan
      3.2.2. Kynurenine
      3.2.3. Anthranilic acid
      3.2.4. Kynurenic acid
      3.2.5. 3-Hydroxykynurenine
      3.2.6. Xanthurenic acid
      3.2.7. 3-Hydroxyanthranilic acid
      3.2.8. Quinolinic acid
4. The abnormal kynurenine pathway links oxidative stress, inflammation, and immune disorder in cardiovascular diseases
    4.1. Immune regulatory role of the kynurenine pathway in atherosclerosis
      4.1.1. Modulation of immunoinflammatory responses by IDO
      4.1.2. Protective role of the kynurenine pathway
    4.2. The kynurenine pathway is associated with the prevalence of cardiovascular disease in chronic renal disease patients
      4.2.1. Relationship to the severity of chronic kidney disease
      4.2.2. Association with the markers of inflammation and oxidative status
      4.2.3. Correlation with cardiovascular diseases
    4.3. Kynurenines affect the cardiovascular system during systemic inflammation
      4.3.1. Vessel relaxation
      4.3.2. Metabolism
    4.4. Activation of the kynurenine pathway in acute severe heart attacks
5. Conclusions
6. Acknowledgements
7. References


The kynurenine (Kyn) pathway is the major route for tryptophan (Trp) metabolism, and it contributes to several fundamental biological processes. Trp is constitutively oxidized by tryptophan 2, 3-dioxygenase in liver cells. In other cell types, it is catalyzed by an alternative inducible indoleamine-pyrrole 2, 3-dioxygenase (IDO) under certain pathophysiological conditions, which consequently increases the formation of Kyn metabolites. IDO is up-regulated in response to inflammatory conditions as a novel marker of immune activation in early atherosclerosis. Besides, IDO and the IDO-related pathway are important mediators of the immunoinflammatory responses in advanced atherosclerosis. In particular, Kyn, 3-hydroxykynurenine, and quinolinic acid are positively associated with inflammation, oxidative stress (SOX), endothelial dysfunction, and carotid artery intima-media thickness values in end-stage renal disease patients. Moreover, IDO is a potential novel contributor to vessel relaxation and metabolism in systemic infections, which is also activated in acute severe heart attacks. The Kyn pathway plays a key role in the increased prevalence of cardiovascular disease by regulating inflammation, SOX, and immune activation.


1. N. J. King and S. R. Thomas: Molecules in focus: indoleamine 2,3-dioxygenase. Int J Biochem Cell Biol, 39 (12), 2167-72 (2007)
DOI: 10.1016/j.biocel.2007.01.004

2. L. Vecsei, L. Szalardy, F. Fulop and J. Toldi: Kynurenines in the CNS: recent advances and new questions. Nat Rev Drug Discov, 12 (1), 64-82 (2013)
DOI: 10.1038/nrd3793

3. J. E. Leklem: Quantitative aspects of tryptophan metabolism in humans and other species: a review. Am J Clin Nutr, 24 (6), 659-72 (1971)

4. D. Zadori, P. Klivenyi, I. Plangar, J. Toldi and L. Vecsei: Endogenous neuroprotection in chronic neurodegenerative disorders: with particular regard to the kynurenines. J Cell Mol Med, 15 (4), 701-17 (2011)
DOI: 10.1111/j.1582-4934.2010.01237.x

5. I. Plangar, D. Zadori, P. Klivenyi, J. Toldi and L. Vecsei: Targeting the kynurenine pathway-related alterations in Alzheimer’s disease: a future therapeutic strategy. J Alzheimers Dis, 24 Suppl 2, 199-209 (2011)

6. N. Muller, A. M. Myint and M. J. Schwarz: Kynurenine pathway in schizophrenia: pathophysiological and therapeutic aspects. Curr Pharm Des, 17 (2), 130-6 (2011)
DOI: 10.2174/138161211795049552

7. J. C. O’Connor, C. Andre, Y. Wang, M. A. Lawson, S. S. Szegedi, J. Lestage, N. Castanon, K. W. Kelley and R. Dantzer: Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin. J Neurosci, 29 (13), 4200-9 (2009)
DOI: 10.1523/JNEUROSCI.5032-08.2009

8. L. McNally, Z. Bhagwagar and J. Hannestad: Inflammation, glutamate, and glia in depression: a literature review. CNS Spectr, 13 (6), 501-10 (2008)

9. K. Pawlak, M. Mysliwiec and D. Pawlak: Hypercoagulability is independently associated with kynurenine pathway activation in dialysed uraemic patients. Thromb Haemost, 102 (1), 49-55 (2009)

10. S. Trabanelli, D. Ocadlikova, C. Evangelisti, S. Parisi and A. Curti: Induction of regulatory T Cells by dendritic cells through indoleamine 2,3-dioxygenase: a potent mechanism of acquired peripheral tolerance. Curr Med Chem, 18 (15), 2234-9 (2011)
DOI: 10.2174/092986711795656054

11. J. B. Sakash, G. I. Byrne, A. Lichtman and P. Libby: Cytokines induce indoleamine 2,3-dioxygenase expression in human atheroma-asociated cells: implications for persistent Chlamydophila pneumoniae infection. Infect Immun, 70 (7), 3959-61 (2002)
DOI: 10.1128/IAI.70.7.3959-3961.2002

12. K. Narui, N. Noguchi, A. Saito, K. Kakimi, N. Motomura, K. Kubo, S. Takamoto and M. Sasatsu: Anti-infectious activity of tryptophan metabolites in the L-tryptophan-L-kynurenine pathway. Biol Pharm Bull, 32 (1), 41-4 (2009)
DOI: 10.1248/bpb.32.41

13. H. Song, H. Park, Y. S. Kim, K. D. Kim, H. K. Lee, D. H. Cho, J. W. Yang and D. Y. Hur: L-kynurenine-induced apoptosis in human NK cells is mediated by reactive oxygen species. Int Immunopharmacol, 11 (8), 932-8 (2011)
DOI: 10.1016/j.intimp.2011.02.005

14. S. S. Zaher, C. Germain, H. Fu, D. F. Larkin and A. J. George: 3-hydroxykynurenine suppresses CD4+ T-cell proliferation, induces T-regulatory-cell development, and prolongs corneal allograft survival. Invest Ophthalmol Vis Sci, 52 (5), 2640-8 (2011)
DOI: 10.1167/iovs.10-5793

15. M. Mailankot, M. M. Staniszewska, H. Butler, M. H. Caprara, S. Howell, B. Wang, C. Doller, L. W. Reneker and R. H. Nagaraj: Indoleamine 2,3-dioxygenase overexpression causes kynurenine-modification of proteins, fiber cell apoptosis and cataract formation in the mouse lens. Lab Invest, 89 (5), 498-512 (2009)
DOI: 10.1038/labinvest.2009.22

16. M. Mailankot and R. H. Nagaraj: Induction of indoleamine 2,3-dioxygenase by interferon-gamma in human lens epithelial cells: apoptosis through the formation of 3-hydroxykynurenine. Int J Biochem Cell Biol, 42 (9), 1446-54 (2010)
DOI: 10.1016/j.biocel.2010.04.014

17. L. Capece, A. Lewis-Ballester, M. A. Marti, D.A. Estrin and S. R. Yeh: Molecular basis for the substrate stereoselectivity in tryptophan dioxygenase. Biochemistry, 50 (50), 10910-8 (2011)
DOI: 10.1021/bi201439m

18. F. Hofmann: Ido brings down the pressure in systemic inflammation. Nat Med, 16 (3), 265-7 (2010)
DOI: 10.1038/nm0310-265

19. O. Takikawa: Biochemical and medical aspects of the indoleamine 2,3-dioxygenase-initiated L-tryptophan metabolism. Biochem Biophys Res Commun, 338 (1), 12-9 (2005)
DOI: 10.1016/j.bbrc.2005.09.032

20. Y. Wang, H. Liu, G. McKenzie, P. K. Witting, J. P. Stasch, M. Hahn, D. Changsirivathanathamrong, B. J. Wu, H.J. Ball, S. R. Thomas, V. Kapoor, D. S. Celermajer, A. L. Mellor, J. F. Keaney, Jr., N. H. Hunt and R. Stocker: Kynurenine is an endothelium-derived relaxing factor produced during inflammation. Nat Med, 16 (3), 279-85 (2010)
DOI: 10.1038/nm.2092

21. D. Changsirivathanathamrong, Y. Wang, D. Rajbhandari, G. J. Maghzal, W. M. Mak, C. Woolfe, J. Duflou, V. Gebski, C. G. dos Remedios, D. S. Celermajer and R. Stocker: Tryptophan metabolism to kynurenine is a potential novel contributor to hypotension in human sepsis. Crit Care Med, 39 (12), 2678-83 (2011)

22. S. Ren, H. Liu, E. Licad and M. A. Correia: Expression of rat liver tryptophan 2,3-dioxygenase in Escherichia coli: structural and functional characterization of the purified enzyme. Arch Biochem Biophys, 333 (1), 96-102 (1996)
DOI: 10.1006/abbi.1996.0368

23. J. M. Leeds, P. J. Brown, G. M. McGeehan, F. K. Brown and J. S. Wiseman: Isotope effects and alternative substrate reactivities for tryptophan 2,3-dioxygenase. J Biol Chem, 268 (24), 17781-6 (1993)

24. T. J. Connor, N. Starr, J. B. O’Sullivan and A. Harkin: Induction of indolamine 2,3-dioxygenase and kynurenine 3-monooxygenase in rat brain following a systemic inflammatory challenge: a role for IFN-gamma? Neurosci Lett, 441 (1), 29-34 (2008)

25. Y. I. Jeong, S. W. Kim, I. D. Jung, J. S. Lee, J. H. Chang, C. M. Lee, S. H. Chun, M. S. Yoon, G. T. Kim, S. W. Ryu, J. S. Kim, Y. K. Shin, W. S. Lee, H. K. Shin, J. D. Lee and Y. M. Park: Curcumin suppresses the induction of indoleamine 2,3-dioxygenase by blocking the Janus-activated kinase-protein kinase Cdelta-STAT1 signaling pathway in interferon-gamma-stimulated murine dendritic cells. J Biol Chem, 284 (6), 3700-8 (2009)
DOI: 10.1074/jbc.M807328200

26. K. Schroecksnadel, B. Frick, C. Winkler and D. Fuchs: Crucial role of interferon-gamma and stimulated macrophages in cardiovascular disease. Curr Vasc Pharmacol, 4 (3), 205-13 (2006)
DOI: 10.2174/157016106777698379

27. A. Chiarugi, M. Calvani, E. Meli, E. Traggiai and F. Moroni: Synthesis and release of neurotoxic kynurenine metabolites by human monocyte-derived macrophages. J Neuroimmunol, 120 (1-2), 190-8 (2001)
DOI: 10.1016/S0165-5728(01) 00418-0

28. D. Alberati-Giani, P. Ricciardi-Castagnoli, C. Kohler and A. M. Cesura: Regulation of the kynurenine metabolic pathway by interferon-gamma in murine cloned macrophages and microglial cells. J Neurochem, 66 (3), 996-1004 (1996)
DOI: 10.1046/j.1471-4159.1996.66030996.x

29. A. L. Mellor and D. H. Munn: IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol, 4 (10), 762-74 (2004)
DOI: 10.1038/nri1457

30. Q. Wang, M. Zhang, Y. Ding, Q. Wang, W. Zhang, P. Song and M. H. Zou: Activation of NAD (P) H Oxidase by Tryptophan-Derived 3-Hydroxykynurenine Accelerates Endothelial Apoptosis and Dysfunction In vivo. Circ Res, 114 (3), 480-92 (2014)
DOI: 10.1161/CIRCRESAHA.114.302113

31. M. C. Cuffy, A. M. Silverio, L. Qin, Y. Wang, R. Eid, G. Brandacher, F. G. Lakkis, D. Fuchs, J. S. Pober and G. Tellides: Induction of indoleamine 2,3-dioxygenase in vascular smooth muscle cells by interferon-gamma contributes to medial immunoprivilege. J Immunol, 179 (8), 5246-54 (2007)
DOI: 10.4049/jimmunol.179.8.5246

32. R. Brouns, R. Verkerk, T. Aerts, D. De Surgeloose, A. Wauters, S. Scharpe and P. P. De Deyn: The role of tryptophan catabolism along the kynurenine pathway in acute ischemic stroke. Neurochem Res, 35 (9), 1315-22 (2010)
DOI: 10.1007/s11064-010-0187-2

33. L. Amori, P. Guidetti, R. Pellicciari, Y. Kajii and R. Schwarcz: On the relationship between the two branches of the kynurenine pathway in the rat brain in vivo. J Neurochem, 109 (2), 316-25 (2009)
DOI: 10.1111/j.1471-4159.2009.05893.x

34. J. Reyes Ocampo, R. Lugo Huitrón, D. González-Esquivel, P. Ugalde- Muñiz, A. Jiménez-Anguiano, B. Pineda, J. Pedraza-Chaverri, C. Ríos and V. Pérez de la Cruz: Kynurenines with Neuroactive and Redox Properties: Relevance to Aging and Brain Diseases. Oxidative Medicine and Cellular Longevity, 2014, 1-22 (2014)
DOI: 10.1155/2014/646909

35. H. A. Walsh and N. P. Botting: Purification and biochemical characterization of some of the properties of recombinant human kynureninase. Eur J Biochem, 269 (8), 2069-74 (2002)
DOI: 10.1046/j.1432-1033.2002.02854.x

36. D. Alberati-Giani, R. Buchli, P. Malherbe, C. Broger, G. Lang, C. Kohler, H. W. Lahm and A. M. Cesura: Isolation and expression of a cDNA clone encoding human kynureninase. Eur J Biochem, 239 (2), 460-8 (1996)
DOI: 10.1111/j.1432-1033.1996.0460u.x

37. S. Okuda, N. Nishiyama, H. Saito and H. Katsuki: 3-Hydroxykynurenine, an endogenous oxidative stress generator, causes neuronal cell death with apoptotic features and region selectivity. J Neurochem, 70 (1), 299-307 (1998)
DOI: 10.1046/j.1471-4159.1998.70010299.x

38. T. W. Stone: Neuropharmacology of quinolinic and kynurenic acids. Pharmacol Rev, 45 (3), 309-79 (1993)

39. R. Schwarcz and R. Pellicciari: Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities. J Pharmacol Exp Ther, 303 (1), 1-10 (2002)
DOI: 10.1124/jpet.102.034439

40. T. W. Stone and L. G. Darlington: Endogenous kynurenines as targets for drug discovery and development. Nat Rev Drug Discov, 1 (8), 609-20 (2002)
DOI: 10.1038/nrd870

41. S. Fukui, R. Schwarcz, S. I. Rapoport, Y. Takada and Q. R. Smith: Blood-brain barrier transport of kynurenines: implications for brain synthesis and metabolism. J Neurochem, 56 (6), 2007-17 (1991)
DOI: 10.1111/j.1471-4159.1991.tb03460.x

42. R. Schwarcz, J. P. Bruno, P. J. Muchowski and H. Q. Wu: Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci, 13 (7), 465-77 (2012)
DOI: 10.1038/nrn3257

43. L. Z. Agudelo, T. Femenia, F. Orhan, M. Porsmyr-Palmertz, M. Goiny, V. Martinez-Redondo, J. C. Correia, M. Izadi, M. Bhat, I. Schuppe-Koistinen, A. T. Pettersson, D. M. Ferreira, A. Krook, R. Barres, J. R. Zierath, S. Erhardt, M. Lindskog and J. L. Ruas: Skeletal muscle PGC-1alpha1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. Cell, 159 (1), 33-45 (2014)
DOI: 10.1016/j.cell.2014.07.051

44. S. Gobaille, V. Kemmel, D. Brumaru, C. Dugave, D. Aunis and M. Maitre: Xanthurenic acid distribution, transport, accumulation and release in the rat brain. J Neurochem, 105 (3), 982-93 (2008)
DOI: 10.1111/j.1471-4159.2008.05219.x

45. S. R. Thomas and R. Stocker: Redox reactions related to indoleamine 2,3-dioxygenase and tryptophan metabolism along the kynurenine pathway. Redox Rep, 4 (5), 199-220 (1999)
DOI: 10.1179/135100099101534927

46. X. Dai and B. T. Zhu: Indoleamine 2,3-dioxygenase tissue distribution and cellular localization in mice: implications for its biological functions. J Histochem Cytochem, 58 (1), 17-28 (2010)
DOI: 10.1369/jhc.2009.953604

47. R. Yoshida, Y. Urade, M. Tokuda and O. Hayaishi: Induction of indoleamine 2,3-dioxygenase in mouse lung during virus infection. Proc Natl Acad Sci U S A, 76 (8), 4084-6 (1979)
DOI: 10.1073/pnas.76.8.4084

48. A. Britan, V. Maffre, S. Tone and J. R. Drevet: Quantitative and spatial differences in the expression of tryptophan-metabolizing enzymes in mouse epididymis. Cell Tissue Res, 324 (2), 301-10 (2006)
DOI: 10.1007/s00441-005-0151-7

49. P. Sedlmayr, A. Blaschitz, R. Wintersteiger, M. Semlitsch, A. Hammer, C. R. MacKenzie, W. Walcher, O. Reich, O. Takikawa and G. Dohr: Localization of indoleamine 2,3-dioxygenase in human female reproductive organs and the placenta. Mol Hum Reprod, 8 (4), 385-91 (2002)
DOI: 10.1093/molehr/8.4.385

50. I. D. Jung, C. M. Lee, Y. I. Jeong, J. S. Lee, W. S. Park, J. Han and Y. M. Park: Differential regulation of indoleamine 2,3-dioxygenase by lipopolysaccharide and interferon gamma in murine bone marrow derived dendritic cells. FEBS Lett, 581 (7), 1449-56 (2007)
DOI: 10.1016/j.febslet.2007.02.073

51. A. Muller, K. Heseler, S. K. Schmidt, K. Spekker, C. R. Mackenzie and W. Daubener: The missing link between indoleamine 2,3-dioxygenase mediated antibacterial and immunoregulatory effects. J Cell Mol Med, 13 (6), 1125-35 (2009)
DOI: 10.1111/j.1582-4934.2008.00542.x

52. D. H. Munn, E. Shafizadeh, J. T. Attwood, I. Bondarev, A. Pashine and A. L. Mellor: Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med, 189 (9), 1363-72 (1999)
DOI: 10.1084/jem.189.9.1363

53. U. Grohmann, C. Orabona, F. Fallarino, C. Vacca, F. Calcinaro, A. Falorni, P. Candeloro, M. L. Belladonna, R. Bianchi, M. C. Fioretti and P. Puccetti: CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat Immunol, 3 (11), 1097-101 (2002)
DOI: 10.1038/ni846

54. J. M. Kremer, R. Westhovens, M. Leon, E. Di Giorgio, R. Alten, S. Steinfeld, A. Russell, M. Dougados, P. Emery, I. F. Nuamah, G. R. Williams, J. C. Becker, D. T. Hagerty and L. W. Moreland: Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med, 349 (20), 1907-15 (2003)
DOI: 10.1056/NEJMoa035075

55. C. M. Robinson, P. T. Hale and J. M. Carlin: The role of IFN-gamma and TNF-alpha-responsive regulatory elements in the synergistic induction of indoleamine dioxygenase. J Interferon Cytokine Res, 25 (1), 20-30 (2005)
DOI: 10.1089/jir.2005.25.20

56. A. M. Hansen, C. Driussi, V. Turner, O. Takikawa and N. H. Hunt: Tissue distribution of indoleamine 2,3-dioxygenase in normal and malaria-infected tissue. Redox Rep, 5 (2-3), 112-5 (2000)

57. A. M. Hansen, H. J. Ball, A. J. Mitchell, J. Miu, O. Takikawa and N. H. Hunt: Increased expression of indoleamine 2,3-dioxygenase in murine malaria infection is predominantly localised to the vascular endothelium. Int J Parasitol, 34 (12), 1309-19 (2004)
DOI: 10.1016/j.ijpara.2004.07.008

58. D. H. Munn and A. L. Mellor: Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J Clin Invest, 117 (5), 1147-54 (2007)
DOI: 10.1172/JCI31178

59. D. H. Munn: Indoleamine 2,3-dioxygenase, tumor-induced tolerance and counter-regulation. Curr Opin Immunol, 18 (2), 220-5 (2006)
DOI: 10.1016/j.coi.2006.01.002

60. Y. Tanizaki, A. Kobayashi, S. Toujima, M. Shiro, M. Mizoguchi, Y. Mabuchi, S. Yagi, S. Minami, O. Takikawa and K. Ino: Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment. Cancer Sci, 105 (8), 966-73 (2014)

61. R. B. Holmgaard, D. Zamarin, D. H. Munn, J. D. Wolchok and J. P. Allison: Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med, 210 (7), 1389-402 (2013)
DOI: 10.1084/jem.20130066

62. H. Soliman, M. Mediavilla-Varela and S. Antonia: Indoleamine 2,3-dioxygenase: is it an immune suppressor? Cancer J, 16 (4), 354-9 (2010)

63. A. Lee, N. Kanuri, Y. Zhang, G. S. Sayuk, E. Li and M. A. Ciorba: IDO1 and IDO2 Non-Synonymous Gene Variants: Correlation with Crohn’s Disease Risk and Clinical Phenotype. PLoS One, 9 (12), e115848 (2014)
DOI: 10.1371/journal.pone.0115848

64. E. Pigott, J. B. DuHadaway, A. J. Muller, S. Gilmour, G. C. Prendergast and L. Mandik-Nayak: 1-Methyl-tryptophan synergizes with methotrexate to alleviate arthritis in a mouse model of arthritis. Autoimmunity, 47 (6), 409-18 (2014)
DOI: 10.3109/08916934.2014.914507

65. A. M. Myint and Y. K. Kim: Network beyond IDO in psychiatric disorders: revisiting neurodegeneration hypothesis. Prog Neuropsychopharmacol Biol Psychiatry, 48, 304-13 (2014)
DOI: 10.1016/j.pnpbp.2013.08.008

66. A. M. Myint and Y. K. Kim: Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression. Med Hypotheses, 61 (5-6), 519-25 (2003)
DOI: 10.1016/S0306-9877(03) 00207-X

67. D. Yu, B. B. Tao, Y. Y. Yang, L. S. Du, S.S.Yang, X. J. He, Y. W. Zhu, J. K. Yan and Q. Yang: The IDO Inhibitor Coptisine Ameliorates Cognitive Impairment in a Mouse Model of Alzheimer’s Disease. J Alzheimers Dis, 43 (1), 291-302 (2015)

68. E. K. Vassiliou, O. M. Kesler, J. H. Tadros and D. Ganea: Bone marrow-derived dendritic cells generated in the presence of resolvin E1 induce apoptosis of activated CD4+ T cells. J Immunol, 181 (7), 4534-44 (2008)
DOI: 10.4049/jimmunol.181.7.4534

69. T. Eleftheriadis, G. Pissas, G. Antoniadi, A. Spanoulis, V. Liakopoulos and I. Stefanidis: Indoleamine 2,3-dioxygenase increases p53 levels in alloreactive human T cells, and both indoleamine 2,3-dioxygenase and p53 suppress glucose uptake, glycolysis and proliferation. Int Immunol, 26 (12), 673-84 (2014)
DOI: 10.1093/intimm/dxu077

70. K. A. Swanson, Y. Zheng, K. M. Heidler, T. Mizobuchi and D. S. Wilkes: CDllc+ cells modulate pulmonary immune responses by production of indoleamine 2,3-dioxygenase. Am J Respir Cell Mol Biol, 30 (3), 311-8 (2004)
DOI: 10.1165/rcmb.2003-0268OC

71. A. M. Alexander, M. Crawford, S. Bertera, W.A. Rudert, O. Takikawa, P. D. Robbins and M. Trucco: Indoleamine 2,3-dioxygenase expression in transplanted NOD Islets prolongs graft survival after adoptive transfer of diabetogenic splenocytes. Diabetes, 51 (2), 356-65 (2002)
DOI: 10.2337/diabetes.51.2.356

72. H. Ito, M. Hoshi, H. Ohtaki, A. Taguchi, K. Ando, T. Ishikawa, Y. Osawa, A. Hara, H. Moriwaki, K. Saito and M. Seishima: Ability of IDO to attenuate liver injury in alpha-galactosylceramide-induced hepatitis model. J Immunol, 185 (8), 4554-60 (2010)
DOI: 10.4049/jimmunol.0904173

73. S. Russo, I. P. Kema, M. R. Fokkema, J. C. Boon, P. H. Willemse, E. G. de Vries, J. A. den Boer and J. Korf: Tryptophan as a link between psychopathology and somatic states. Psychosom Med, 65 (4), 665-71 (2003)
DOI: 10.1097/01.PSY.0000078188.74020.CC

74. H. Kim, L. Chen, G. Lim, B. Sung, S. Wang, M. F. McCabe, G. Rusanescu, L. Yang, Y. Tian and J. Mao: Brain indoleamine 2,3-dioxygenase contributes to the comorbidity of pain and depression. J Clin Invest, 122 (8), 2940-54 (2012)
DOI: 10.1172/JCI61884

75. L. Pilotte, P. Larrieu, V. Stroobant, D. Colau, E. Dolusic, R. Frederick, E. De Plaen, C. Uyttenhove, J. Wouters, B. Masereel and B. J. Van den Eynde: Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proc Natl Acad Sci U S A, 109 (7), 2497-502 (2012)
DOI: 10.1073/pnas.1113873109

76. F. Forouhar, J. L. Anderson, C. G. Mowat, S. M. Vorobiev, A. Hussain, M. Abashidze, C. Bruckmann, S. J. Thackray, J. Seetharaman, T. Tucker, R. Xiao, L. C. Ma, L. Zhao, T. B. Acton, G. T. Montelione, S. K. Chapman and L. Tong: Molecular insights into substrate recognition and catalysis by tryptophan 2,3-dioxygenase. Proc Natl Acad Sci U S A, 104 (2), 473-8 (2007)
DOI: 10.1073/pnas.0610007104

77. W. De Laurentis, L. Khim, J. L. Anderson, A. Adam, K. A. Johnson, R. S. Phillips, S.K.Chapman, K. H. van Pee and J. H. Naismith: The second enzyme in pyrrolnitrin biosynthetic pathway is related to the heme-dependent dioxygenase superfamily. Biochemistry, 46 (43), 12393-404 (2007)
DOI: 10.1021/bi7012189

78. S. Suzuki, S. Tone, O. Takikawa, T. Kubo, I.Kohno and Y. Minatogawa: Expression of indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase in early concepti. Biochem J, 355 (Pt 2), 425-9 (2001)
DOI: 10.1042/0264-6021:3550425

79. I. Ishiguro, J. Naito, K. Saito and Y. Nagamura: Skin L-tryptophan-2,3-dioxygenase and rat hair growth. FEBS Lett, 329 (1-2), 178-82 (1993)
DOI: 10.1016/0014-5793(93) 80217-I

80. M. Kanai, H. Funakoshi, H. Takahashi, T.Hayakawa, S. Mizuno, K. Matsumoto and T. Nakamura: Tryptophan 2,3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice. Mol Brain, 2, 8 (2009)

81. M. A. Thevandavakkam, R. Schwarcz, P.J. Muchowski and F. Giorgini: Targeting kynurenine 3-monooxygenase (KMO): implications for therapy in Huntington’s disease. CNS Neurol Disord Drug Targets, 9 (6), 791-800 (2010)
DOI: 10.2174/187152710793237430

82. F. Giorgini, T. Moller, W. Kwan, D. Zwilling, J.L. Wacker, S. Hong, L. C. Tsai, C. S. Cheah, R. Schwarcz, P. Guidetti and P. J. Muchowski: Histone deacetylase inhibition modulates kynurenine pathway activation in yeast, microglia, and mice expressing a mutant huntingtin fragment. J Biol Chem, 283 (12), 7390-400 (2008)
DOI: 10.1074/jbc.M708192200

83. J. Breton, N. Avanzi, S. Magagnin, N. Covini, G. Magistrelli, L. Cozzi and A. Isacchi: Functional characterization and mechanism of action of recombinant human kynurenine 3-hydroxylase. Eur J Biochem, 267 (4), 1092-9 (2000)
DOI: 10.1046/j.1432-1327.2000.01104.x

84. D. M. Lowe, M. Gee, C. Haslam, B. Leavens, E. Christodoulou, P. Hissey, P. Hardwicke, A. Argyrou, S. P. Webster, D. J. Mole, K. Wilson, M. Binnie, B. A. Yard, T. Dean, J. Liddle, I. Uings and J. P. Hutchinson: Lead Discovery for Human Kynurenine 3-Monooxygenase by High-Throughput RapidFire Mass Spectrometry. J Biomol Screen (2013)

85. D. Zwilling, S. Y. Huang, K. V. Sathyasaikumar, F. M. Notarangelo, P. Guidetti, H. Q. Wu, J. Lee, J. Truong, Y. Andrews-Zwilling, E. W. Hsieh, J. Y. Louie, T. Wu, K. Scearce-Levie, C. Patrick, A. Adame, F. Giorgini, S. Moussaoui, G. Laue, A. Rassoulpour, G. Flik, Y. Huang, J. M. Muchowski, E. Masliah, R. Schwarcz and P. J. Muchowski: Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration. Cell, 145 (6), 863-74 (2011)
DOI: 10.1016/j.cell.2011.05.020

86. F. Giorgini, P. Guidetti, Q. Nguyen, S. C. Bennett and P. J. Muchowski: A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease. Nat Genet, 37 (5), 526-31 (2005)
DOI: 10.1038/ng1542

87. F. Moroni, R. Carpenedo, A. Cozzi, E. Meli, A. Chiarugi and D. E. Pellegrini-Giampietro: Studies on the neuroprotective action of kynurenine mono-oxygenase inhibitors in post-ischemic brain damage. Adv Exp Med Biol, 527, 127-36 (2003)
DOI: 10.1007/978-1-4615-0135-0_15

88. P. Guidetti, E. Okuno and R. Schwarcz: Characterization of rat brain kynurenine aminotransferases I and II. J Neurosci Res, 50 (3), 457-65 (1997)
DOI: 10.1002/(SICI) 1097-4547(19971101) 50:3<457::AID-JNR12>3.0.CO;2-3
DOI: 10.1002/(SICI) 1097-4547(19971101) 50:3<457::AID-JNR12>3.3.CO;2-W

89. P. Yu, Z. Li, L. Zhang, D. A. Tagle and T. Cai: Characterization of kynurenine aminotransferase III, a novel member of a phylogenetically conserved KAT family. Gene, 365, 111-8 (2006)
DOI: 10.1016/j.gene.2005.09.034

90. Q. Han, H. Robinson, T. Cai, D. A. Tagle and J. Li: Biochemical and structural properties of mouse kynurenine aminotransferase III. Mol Cell Biol, 29 (3), 784-93 (2009)
DOI: 10.1128/MCB.01272-08

91. P. Guidetti, L. Amori, M. T. Sapko, E. Okuno and R. Schwarcz: Mitochondrial aspartate aminotransferase: a third kynurenate-producing enzyme in the mammalian brain. J Neurochem, 102 (1), 103-11 (2007)
DOI: 10.1111/j.1471-4159.2007.04556.x

92. T. Noguchi, J. Nakamura and R. Kido: Kynurenine pyruvate transaminase and its inhibitor in rat intestine. Life Sci, 13 (7), 1001-10 (1973)
DOI: 10.1016/0024-3205(73) 90091-X

93. P. Yu, D. M. Mosbrook and D. A. Tagle: Genomic organization and expression analysis of mouse kynurenine aminotransferase II, a possible factor in the pathophysiology of Huntington’s disease. Mamm Genome, 10 (9), 845-52 (1999)
DOI: 10.1007/s003359901102

94. R. Kapoor, E. Okuno, R. Kido and V. Kapoor: Immuno-localization of kynurenine aminotransferase (KAT) in the rat medulla and spinal cord. Neuroreport, 8 (16), 3619-23 (1997)
DOI: 10.1097/00001756-199711100-00039

95. J. Kawai, E. Okuno and R. Kido: Organ distribution of rat kynureninase and changes of its activity during development. Enzyme, 39 (4), 181-9 (1988)

96. G. Melillo, T. Musso, A. Sica, L. S. Taylor, G. W. Cox and L. Varesio: A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter. J Exp Med, 182 (6), 1683-93 (1995)
DOI: 10.1084/jem.182.6.1683

97. M. P. Heyes, K. Saito, E. O. Major, S.Milstien, S. P. Markey and J. H. Vickers: A mechanism of quinolinic acid formation by brain in inflammatory neurological disease. Attenuation of synthesis from L-tryptophan by 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate. Brain, 116 ( Pt 6), 1425-50 (1993)
DOI: 10.1093/brain/116.6.1425

98. L. Y. Frolova, A. Y. Grigorieva, M. A. Sudomoina and L. L. Kisselev: The human gene encoding tryptophanyl-tRNA synthetase: interferon-response elements and exon-intron organization. Gene, 128 (2), 237-45 (1993)
DOI: 10.1016/0378-1119(93) 90568-N

99. A. Tsopmo, B. W. Diehl-Jones, R. E. Aluko, D. D. Kitts, I. Elisia and J. K. Friel: Tryptophan released from mother’s milk has antioxidant properties. Pediatr Res, 66 (6), 614-8 (2009)
DOI: 10.1203/PDR.0b013e3181be9e7e

100. O. K. Bitzer-Quintero, A. J. Davalos-Marin, G. G. Ortiz, A. R. Meza, B. M. Torres-Mendoza, R. G. Robles, V. C. Huerta and C. Beas-Zarate: Antioxidant activity of tryptophan in rats under experimental endotoxic shock. Biomed Pharmacother, 64 (1), 77-81 (2010)
DOI: 10.1016/j.biopha.2009.07.002

101. M. Pazos, M. L. Andersen and L. H. Skibsted: Amino acid and protein scavenging of radicals generated by iron/hydroperoxide system: an electron spin resonance spin trapping study. J Agric Food Chem, 54 (26), 10215-21 (2006)
DOI: 10.1021/jf062134n

102. G. Weiss, A. Diez-Ruiz, C. Murr, I. Theur and D. Fuchs: Tryptophan Metabolites as Scavengers of Reactive Oxygen and Chlorine Species. In: Pteridines. (2002)

103. K. Goda, M. Hisaoka and T. Ueda: Photoinduced electron transfer reaction from N-formyl-L-kynurenine and L-kynurenine to cytochrome C. Biochem Int, 15 (3), 635-43 (1987)

104. K. J. Reszka, P. Bilski, C. F. Chignell and J. Dillon: Free radical reactions photosensitized by the human lens component, kynurenine: an EPR and spin trapping investigation. Free Radic Biol Med, 20 (1), 23-34 (1996)
DOI: 10.1016/0891-5849(95) 02018-7

105. S. Vazquez, J. A. Aquilina, J. F. Jamie, M. M. Sheil and R. J. Truscott: Novel protein modification by kynurenine in human lenses. J Biol Chem, 277 (7), 4867-73 (2002)
DOI: 10.1074/jbc.M107529200

106. L. Dong-Ruyl, M. Sawada and K. Nakano: Tryptophan and its metabolite, kynurenine, stimulate expression of nerve growth factor in cultured mouse astroglial cells. Neurosci Lett, 244 (1), 17-20 (1998)
DOI: 10.1016/S0304-3940(98) 00120-7

107. G. J. Guillemin, S. J. Kerr, G. A. Smythe, D.G.Smith, V. Kapoor, P. J. Armati, J. Croitoru and B. J. Brew: Kynurenine pathway metabolism in human astrocytes: a paradox for neuronal protection. J Neurochem, 78 (4), 842-53 (2001)
DOI: 10.1046/j.1471-4159.2001.00498.x

108. C. Speciale and R. Schwarcz: Uptake of kynurenine into rat brain slices. J Neurochem, 54 (1), 156-63 (1990)
DOI: 10.1111/j.1471-4159.1990.tb13296.x

109. S. Gaubert, M. Bouchaut, V. Brumas and G. Berthon: Copper--ligand interactions and the physiological free radical processes. Part 3. Influence of histidine, salicylic acid and anthranilic acid on copper-driven Fenton chemistry in vitro. Free Radic Res, 32 (5), 451-61 (2000)
DOI: 10.1080/10715760000300451

110. H. Miche, V. Brumas and G. Berthon: Copper (II) interactions with nonsteroidal antiinflammatory agents. II. Anthranilic acid as a potential. OH-inactivating ligand. J Inorg Biochem, 68 (1), 27-38 (1997)
DOI: 10.1016/S0162-0134(97) 00005-6

111. P. J. Birch, C. J. Grossman and A. G. Hayes: Kynurenic acid antagonises responses to NMDA via an action at the strychnine-insensitive glycine receptor. Eur J Pharmacol, 154 (1), 85-7 (1988)
DOI: 10.1016/0014-2999(88) 90367-6

112. C. Hilmas, E. F. Pereira, M. Alkondon, A. Rassoulpour, R. Schwarcz and E. X. Albuquerque: The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications. J Neurosci, 21 (19), 7463-73 (2001)

113. A. Konradsson-Geuken, H. Q. Wu, C. R. Gash, K. S. Alexander, A. Campbell, Y. Sozeri, R. Pellicciari, R. Schwarcz and J. P. Bruno: Cortical kynurenic acid bi-directionally modulates prefrontal glutamate levels as assessed by microdialysis and rapid electrochemistry. Neuroscience, 169 (4), 1848-59 (2010)
DOI: 10.1016/j.neuroscience.2010.05.052

114. H. Q. Wu, E. F. Pereira, J. P. Bruno, R. Pellicciari, E. X. Albuquerque and R. Schwarcz: The astrocyte-derived alpha7 nicotinic receptor antagonist kynurenic acid controls extracellular glutamate levels in the prefrontal cortex. J Mol Neurosci, 40 (1-2), 204-10 (2010)

115. A. Zmarowski, H. Q. Wu, J. M. Brooks, M. C. Potter, R. Pellicciari, R. Schwarcz and J. P. Bruno: Astrocyte-derived kynurenic acid modulates basal and evoked cortical acetylcholine release. Eur J Neurosci, 29 (3), 529-38 (2009)
DOI: 10.1111/j.1460-9568.2008.06594.x

116. W. A. Turski, M. Nakamura, W. P. Todd, B. K. Carpenter, W. O. Whetsell, Jr. and R. Schwarcz: Identification and quantification of kynurenic acid in human brain tissue. Brain Res, 454 (1-2), 164-9 (1988)
DOI: 10.1016/0006-8993(88) 90815-3

117. K. J. Swartz, W. R. Matson, U. MacGarvey, E. A. Ryan and M. F. Beal: Measurement of kynurenic acid in mammalian brain extracts and cerebrospinal fluid by high-performance liquid chromatography with fluorometric and coulometric electrode array detection. Anal Biochem, 185 (2), 363-76 (1990)
DOI: 10.1016/0003-2697(90) 90309-W

118. J. Parada-Turska, W. Rzeski, W. Zgrajka, M. Majdan, M. Kandefer-Szerszen and W. Turski: Kynurenic acid, an endogenous constituent of rheumatoid arthritis synovial fluid, inhibits proliferation of synoviocytes in vitro. Rheumatol Int, 26 (5), 422-6 (2006)
DOI: 10.1007/s00296-005-0057-4

119. R. Rejdak, T. Zarnowski, W. A. Turski, E. Okuno, T. Kocki, Z. Zagorski, K. Kohler, E. Guenther and E. Zrenner: Presence of kynurenic acid and kynurenine aminotransferases in the inner retina. Neuroreport, 12 (17), 3675-8 (2001)
DOI: 10.1097/00001756-200112040-00014

120. F. Moroni, A. Cozzi, M. Sili and G. Mannaioni: Kynurenic acid: a metabolite with multiple actions and multiple targets in brain and periphery. J Neural Transm, 119 (2), 133-9 (2012)
DOI: 10.1007/s00702-011-0763-x

121. K. Pawlak, M. Mysliwiec and D. Pawlak: Haemostatic system, biochemical profiles, kynurenines and the prevalence of cardiovascular disease in peritoneally dialyzed patients. Thromb Res, 125 (2), e40-5 (2010)
DOI: 10.1016/j.thromres.2009.08.009

122. K. Pawlak, M. Mysliwiec and D. Pawlak: Hyperhomocysteinemia and the presence of cardiovascular disease are associated with kynurenic acid levels and carotid atherosclerosis in patients undergoing continuous ambulatory peritoneal dialysis. Thromb Res, 129 (6), 704-9 (2012)
DOI: 10.1016/j.thromres.2011.08.016

123. J. Wang, N. Simonavicius, X. Wu, G. Swaminath, J. Reagan, H. Tian and L. Ling: Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. J Biol Chem, 281 (31), 22021-8 (2006)
DOI: 10.1074/jbc.M603503200

124. H. Ohshiro, H. Tonai-Kachi and K. Ichikawa: GPR35 is a functional receptor in rat dorsal root ganglion neurons. Biochem Biophys Res Commun, 365 (2), 344-8 (2008)
DOI: 10.1016/j.bbrc.2007.10.197

125. R. Hardeland, B. K. Zsizsik, B. Poeggeler, B. Fuhrberg, S. Holst and A. Coto-Montes: Indole-3-pyruvic and -propionic acids, kynurenic acid, and related metabolites as luminophores and free-radical scavengers. Adv Exp Med Biol, 467, 389-95 (1999)
DOI: 10.1007/978-1-4615-4709-9_49

126. R. Lugo-Huitron, T. Blanco-Ayala, P. Ugalde-Muniz, P. Carrillo-Mora, J. Pedraza-Chaverri, D. Silva-Adaya, P. D. Maldonado, I. Torres, E. Pinzon, E. Ortiz-Islas, T. Lopez, E. Garcia, B. Pineda, M. Torres-Ramos, A. Santamaria and V. P. La Cruz: On the antioxidant properties of kynurenic acid: free radical scavenging activity and inhibition of oxidative stress. Neurotoxicol Teratol, 33 (5), 538-47 (2011)
DOI: 10.1016/j.ntt.2011.07.002

127. J. Stazka, P. Luchowski, M. Wielosz, Z. Kleinrok and E. M. Urbanska: Endothelium-dependent production and liberation of kynurenic acid by rat aortic rings exposed to L-kynurenine. Eur J Pharmacol, 448 (2-3), 133-7 (2002)
DOI: 10.1016/S0014-2999(02) 01943-X

128. K. Wejksza, W. Rzeski and W. A. Turski: Kynurenic acid protects against the homocysteine-induced impairment of endothelial cells. Pharmacol Rep, 61 (4), 751-6 (2009)
DOI: 10.1016/S1734-1140(09) 70130-6

129. T. Ishii, H. Iwahashi, R. Sugata and R. Kido: Formation of hydroxanthommatin-derived radical in the oxidation of 3-hydroxykynurenine. Arch Biochem Biophys, 294 (2), 616-22 (1992)
DOI: 10.1016/0003-9861(92) 90733-D

130. H. Wei, P. Leeds, R. W. Chen, W. Wei, Y. Leng, D. E. Bredesen and D. M. Chuang: Neuronal apoptosis induced by pharmacological concentrations of 3-hydroxykynurenine: characterization and protection by dantrolene and Bcl-2 overexpression. J Neurochem, 75 (1), 81-90 (2000)
DOI: 10.1046/j.1471-4159.2000.0750081.x

131. S. Okuda, N. Nishiyama, H. Saito and H. Katsuki: Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine. Proc Natl Acad Sci U S A, 93 (22), 12553-8 (1996)
DOI: 10.1073/pnas.93.22.12553

132. L. E. Goldstein, M. C. Leopold, X. Huang, C. S. Atwood, A. J. Saunders, M. Hartshorn, J.T.Lim, K. Y. Faget, J. A. Muffat, R. C. Scarpa, L. T. Chylack, Jr., E. F. Bowden, R. E. Tanzi and A. I. Bush: 3-Hydroxykynurenine and 3-hydroxyanthranilic acid generate hydrogen peroxide and promote alpha-crystallin cross-linking by metal ion reduction. Biochemistry, 39 (24), 7266-75 (2000)
DOI: 10.1021/bi992997s

133. A. Korlimbinis, P. G. Hains, R. J. W. Truscott and J. A. Aquilina: 3-Hydroxykynurenine Oxidizes α-Crystallin: Potential Role in Cataractogenesis†. Biochemistry, 45 (6), 1852-1860 (2006)
DOI: 10.1021/bi051737+

134. J. Dillon, S. Garcia Castineiras, M. A. Santiago and A. Spector: The endopeptidase-resistant protein fraction from human cataractous lenses. Exp Eye Res, 39 (1), 95-106 (1984)
DOI: 10.1016/0014-4835(84) 90118-0

135. H. J. Lee, J. H. Bach, H. S. Chae, S. H. Lee, W. S. Joo, S. H. Choi, K. Y. Kim, W. B. Lee and S. S. Kim: Mitogen-activated protein kinase/extracellular signal-regulated kinase attenuates 3-hydroxykynurenine-induced neuronal cell death. J Neurochem, 88 (3), 647-56 (2004)
DOI: 10.1111/j.1471-4159.2004.02191.x

136. Y. Nakagami, H. Saito and H. Katsuki: 3-Hydroxykynurenine toxicity on the rat striatum in vivo. Jpn J Pharmacol, 71 (2), 183-6 (1996)
DOI: 10.1254/jjp.71.183

137. G. T. Bryan, R. R. Brown and J. M. Price: Mouse Bladder Carcinogenicity of Certain Tryptophan Metabolites and Other Aromatic Nitrogen Compounds Suspended in Cholesterol. Cancer Res, 24, 596-602 (1964)

138. S. Christen, E. Peterhans and R. Stocker: Antioxidant activities of some tryptophan metabolites: possible implication for inflammatory diseases. Proc Natl Acad Sci U S A, 87 (7), 2506-10 (1990)
DOI: 10.1073/pnas.87.7.2506

139. N. Goshima, A. Wadano and K. Miura: 3-Hydroxykynurenine as O2-. scavenger in the blowfly, Aldrichina grahami. Biochem Biophys Res Commun, 139 (2), 666-72 (1986)
DOI: 10.1016/S0006-291X(86) 80042-0

140. G. I. Giles, C. A. Collins, T. W. Stone and C. Jacob: Electrochemical and in vitro evaluation of the redox-properties of kynurenine species. Biochem Biophys Res Commun, 300 (3), 719-24 (2003)
DOI: 10.1016/S0006-291X(02) 02917-0

141. K. Murakami, M. Ito and M. Yoshino: Xanthurenic acid inhibits metal ion-induced lipid peroxidation and protects NADP-isocitrate dehydrogenase from oxidative inactivation. J Nutr Sci Vitaminol (Tokyo), 47 (4), 306-10 (2001)
DOI: 10.3177/jnsv.47.306

142. V. L. Lima, F. Dias, R. D. Nunes, L. O. Pereira, T. S. Santos, L. B. Chiarini, T. D. Ramos, B. J. Silva-Mendes, J. Perales, R. H. Valente and P. L. Oliveira: The antioxidant role of xanthurenic acid in the Aedes aegypti midgut during digestion of a blood meal. PLoS One, 7 (6), e38349 (2012)
DOI: 10.1371/journal.pone.0038349

143. K. Murakami, M. Haneda and M. Yoshino: Prooxidant action of xanthurenic acid and quinoline compounds: role of transition metals in the generation of reactive oxygen species and enhanced formation of 8-hydroxy-2’-deoxyguanosine in DNA. Biometals, 19 (4), 429-35 (2006)
DOI: 10.1007/s10534-005-4528-6

144. H. Malina, C. Richter, B. Frueh and O. M. Hess: Lens epithelial cell apoptosis and intracellular Ca2+ increase in the presence of xanthurenic acid. BMC Ophthalmol, 2, 1 (2002)
DOI: 10.1186/1471-2415-2-1

145. H. Z. Malina, C. Richter, M. Mehl and O. M. Hess: Pathological apoptosis by xanthurenic acid, a tryptophan metabolite: activation of cell caspases but not cytoskeleton breakdown. BMC Physiol, 1, 7 (2001)
DOI: 10.1186/1472-6793-1-7

146. J. E. Roberts, J. F. Wishart, L. Martinez and C. F. Chignell: Photochemical studies on xanthurenic acid. Photochem Photobiol, 72 (4), 467-71 (2000)
DOI: 10.1562/0031-8655(2000) 072<0467:PSOXA>2.0.CO;2

147. J. E. Roberts, E. L. Finley, S. A. Patat and K. L. Schey: Photooxidation of lens proteins with xanthurenic acid: a putative chromophore for cataractogenesis. Photochem Photobiol, 74 (5), 740-4 (2001)
DOI: 10.1562/0031-8655(2001) 0740740POLPWX2.0.CO2

148. E. Quagliariello, S. Papa, C. Saccone and A. Alifano: Effect of 3-hydroxyanthranilic acid on the mitochondrial respiratory system. Biochem J, 91 (1), 137-46 (1964)

149. T. Morita, K. Saito, M. Takemura, N. Maekawa, S. Fujigaki, H. Fujii, H. Wada, S. Takeuchi, A. Noma and M. Seishima: 3-Hydroxyanthranilic acid, an L-tryptophan metabolite, induces apoptosis in monocyte-derived cells stimulated by interferon-gamma. Ann Clin Biochem, 38 (Pt 3), 242-51 (2001)
DOI: 10.1258/0004563011900461

150. F. Fallarino, U. Grohmann, C. Vacca, R. Bianchi, C. Orabona, A. Spreca, M. C. Fioretti and P. Puccetti: T cell apoptosis by tryptophan catabolism. Cell Death Differ, 9 (10), 1069-77 (2002)
DOI: 10.1038/sj.cdd.4401073

151. S. M. Lee, Y. S. Lee, J. H. Choi, S. G. Park, I. W. Choi, Y. D. Joo, W. S. Lee, J. N. Lee, I. Choi and S. K. Seo: Tryptophan metabolite 3-hydroxyanthranilic acid selectively induces activated T cell death via intracellular GSH depletion. Immunol Lett, 132 (1-2), 53-60 (2010)

152. T. Hayashi, J. H. Mo, X. Gong, C. Rossetto, A. Jang, L. Beck, G. I. Elliott, I. Kufareva, R.Abagyan, D. H. Broide, J. Lee and E. Raz: 3-Hydroxyanthranilic acid inhibits PDK1 activation and suppresses experimental asthma by inducing T cell apoptosis. Proc Natl Acad Sci U S A, 104 (47), 18619-24 (2007)
DOI: 10.1073/pnas.0709261104

153. S. R. Thomas, P. K. Witting and R. Stocker: 3-Hydroxyanthranilic acid is an efficient, cell-derived co-antioxidant for alpha-tocopherol, inhibiting human low density lipoprotein and plasma lipid peroxidation. J Biol Chem, 271 (51), 32714-21 (1996)
DOI: 10.1074/jbc.271.51.32714

154. D. Alberati-Giani, P. Malherbe, P. Ricciardi-Castagnoli, C. Kohler, S. Denis-Donini and A. M. Cesura: Differential regulation of indoleamine 2,3-dioxygenase expression by nitric oxide and inflammatory mediators in IFN-gamma-activated murine macrophages and microglial cells. J Immunol, 159 (1), 419-26 (1997)

155. G. S. Oh, H. O. Pae, B. M. Choi, S. C. Chae, H. S. Lee, D. G. Ryu and H. T. Chung: 3-Hydroxyanthranilic acid, one of metabolites of tryptophan via indoleamine 2,3-dioxygenase pathway, suppresses inducible nitric oxide synthase expression by enhancing heme oxygenase-1 expression. Biochem Biophys Res Commun, 320 (4), 1156-62 (2004)
DOI: 10.1016/j.bbrc.2004.06.061

156. H. O. Pae, G. S. Oh, B. S. Lee, J. S. Rim, Y. M. Kim and H. T. Chung: 3-Hydroxyanthranilic acid, one of L-tryptophan metabolites, inhibits monocyte chemoattractant protein-1 secretion and vascular cell adhesion molecule-1 expression via heme oxygenase-1 induction in human umbilical vein endothelial cells. Atherosclerosis, 187 (2), 274-84 (2006)
DOI: 10.1016/j.atherosclerosis.2005.09.010

157. A. Latini, M. Rodriguez, R. Borba Rosa, K. Scussiato, G. Leipnitz, D. Reis de Assis, G. da Costa Ferreira, C. Funchal, M. C. Jacques-Silva, L. Buzin, R. Giugliani, A. Cassina, R. Radi and M. Wajner: 3-Hydroxyglutaric acid moderately impairs energy metabolism in brain of young rats. Neuroscience, 135 (1), 111-20 (2005)
DOI: 10.1016/j.neuroscience.2005.05.013

158. G. Leipnitz, C. Schumacher, K. B. Dalcin, K. Scussiato, A. Solano, C. Funchal, C. S. Dutra-Filho, A. T. Wyse, C. M. Wannmacher, A. Latini and M. Wajner: In vitro evidence for an antioxidant role of 3-hydroxykynurenine and 3-hydroxyanthranilic acid in the brain. Neurochem Int, 50 (1), 83-94 (2007)
DOI: 10.1016/j.neuint.2006.04.017

159. L. G. Darlington, C. M. Forrest, G. M. Mackay, R. A. Smith, A. J. Smith, N. Stoy and T. W. Stone: On the Biological Importance of the 3-hydroxyanthranilic Acid: Anthranilic Acid Ratio. Int J Tryptophan Res, 3, 51-9 (2010)

160. G. J. Guillemin: Quinolinic acid, the inescapable neurotoxin. FEBS J, 279 (8), 1356-65 (2012)
DOI: 10.1111/j.1742-4658.2012.08493.x

161. Y. M. Bordelon, M. F. Chesselet, D. Nelson, F. Welsh and M. Erecinska: Energetic dysfunction in quinolinic acid-lesioned rat striatum. J Neurochem, 69 (4), 1629-39 (1997)
DOI: 10.1046/j.1471-4159.1997.69041629.x

162. H. Baran, K. Staniek, B. Kepplinger, L.Gille, K. Stolze and H. Nohl: Kynurenic acid influences the respiratory parameters of rat heart mitochondria. Pharmacology, 62 (2), 119-23 (2001)
DOI: 10.1159/000056082

163. A. Santamaria, M. E. Jimenez-Capdeville, A.Camacho, E. Rodriguez-Martinez, A.Flores and S. Galvan-Arzate: In vivo hydroxyl radical formation after quinolinic acid infusion into rat corpus striatum. Neuroreport, 12 (12), 2693-6 (2001)
DOI: 10.1097/00001756-200108280-00020

164. W. M. Behan, M. McDonald, L. G. Darlington and T. W. Stone: Oxidative stress as a mechanism for quinolinic acid-induced hippocampal damage: protection by melatonin and deprenyl. Br J Pharmacol, 128 (8), 1754-60 (1999)
DOI: 10.1038/sj.bjp.0702940

165. G. Leipnitz, C. Schumacher, K. Scussiato, K. B. Dalcin, C. M. Wannmacher, A. T. Wyse, C. S. Dutra-Filho, M. Wajner and A. Latini: Quinolinic acid reduces the antioxidant defenses in cerebral cortex of young rats. Int J Dev Neurosci, 23 (8), 695-701 (2005)
DOI: 10.1016/j.ijdevneu.2005.08.004

166. I. Carmona-Ramirez, A. Santamaria, J. C. Tobon-Velasco, M. Orozco-Ibarra, I. G. Gonzalez-Herrera, J. Pedraza-Chaverri and P. D. Maldonado: Curcumin restores Nrf2 levels and prevents quinolinic acid-induced neurotoxicity. J Nutr Biochem, 24 (1), 14-24 (2013)
DOI: 10.1016/j.jnutbio.2011.12.010

167. E. Rodriguez-Martinez, A. Camacho, P. D. Maldonado, J. Pedraza-Chaverri, D. Santamaria, S. Galvan-Arzate and A. Santamaria: Effect of quinolinic acid on endogenous antioxidants in rat corpus striatum. Brain Res, 858 (2), 436-9 (2000)
DOI: 10.1016/S0006-8993(99) 02474-9

168. V. Perez-De La Cruz, C. Gonzalez-Cortes, S. Galvan-Arzate, O. N. Medina-Campos, F. Perez-Severiano, S. F. Ali, J. Pedraza-Chaverri and A. Santamaria: Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington’s disease in rats: protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinate iron (III). Neuroscience, 135 (2), 463-74 (2005)
DOI: 10.1016/j.neuroscience.2005.06.027

169. D. Santiago-Lopez, B. Vazquez-Roman, V. Perez-de La Cruz, D. Barrera, D. Rembao, C. Salinas-Lara, J. Pedraza-Chaverri, S. Galvan-Arzate, S. F. Ali and A. Santamaria: Peroxynitrite decomposition catalyst, iron metalloporphyrin, reduces quinolinate-induced neurotoxicity in rats. Synapse, 54 (4), 233-8 (2004)
DOI: 10.1002/syn.20084

170. E. Rodriguez, M. Mendez-Armenta, J. Villeda-Hernandez, S. Galvan-Arzate, R. Barroso-Moguel, F. Rodriguez, C. Rios and A. Santamaria: Dapsone prevents morphological lesions and lipid peroxidation induced by quinolinic acid in rat corpus striatum. Toxicology, 139 (1-2), 111-8 (1999)
DOI: 10.1016/S0300-483X(99) 00116-X

171. A. Santamaria, S. Galvan-Arzate, V. Lisy, S. F. Ali, H. M. Duhart, L. Osorio-Rico, C. Rios and F. St’astny: Quinolinic acid induces oxidative stress in rat brain synaptosomes. Neuroreport, 12 (4), 871-4 (2001)
DOI: 10.1097/00001756-200103260-00049

172. N. Braidy, R. Grant, S. Adams, B. J. Brew and G. J. Guillemin: Mechanism for quinolinic acid cytotoxicity in human astrocytes and neurons. Neurotox Res, 16 (1), 77-86 (2009)
DOI: 10.1007/s12640-009-9051-z

173. N. Braidy, R. Grant, B. J. Brew, S. Adams, T. Jayasena and G. J. Guillemin: Effects of Kynurenine Pathway Metabolites on Intracellular NAD Synthesis and Cell Death in Human Primary Astrocytes and Neurons. Int J Tryptophan Res, 2, 61-9 (2009)

174. R. Lugo-Huitron, P. Ugalde Muniz, B. Pineda, J. Pedraza-Chaverri, C. Rios and V. Perez-de la Cruz: Quinolinic acid: an endogenous neurotoxin with multiple targets. Oxid Med Cell Longev, 2013, 104024 (2013)

175. S. Stipek, F. Stastny, J. Platenik, J. Crkovska and T. Zima: The effect of quinolinate on rat brain lipid peroxidation is dependent on iron. Neurochem Int, 30 (2), 233-7 (1997)
DOI: 10.1016/S0197-0186(97) 90002-4

176. J. Platenik, P. Stopka, M. Vejrazka and S. Stipek: Quinolinic acid-iron (ii) complexes: slow autoxidation, but enhanced hydroxyl radical production in the Fenton reaction. Free Radic Res, 34 (5), 445-59 (2001)
DOI: 10.1080/10715760100300391

177. K. Goda, R. Kishimoto, S. Shimizu, Y.Hamane and M. Ueda: Quinolinic acid and active oxygens. Possible contribution of active Oxygens during cell death in the brain. Adv Exp Med Biol, 398, 247-54 (1996)
DOI: 10.1007/978-1-4613-0381-7_38

178. P. Niinisalo, A. Raitala, M. Pertovaara, S. S. Oja, T. Lehtimaki, M. Kahonen, A. Reunanen, A. Jula, L. Moilanen, Y. A. Kesaniemi, M.S.Nieminen and M. Hurme: Indoleamine 2,3-dioxygenase activity associates with cardiovascular risk factors: the Health 2000 study. Scand J Clin Lab Invest, 68 (8), 767-70 (2008)
DOI: 10.1080/00365510802245685

179. E. R. Pedersen, G. F. Svingen, H. Schartum-Hansen, P. M. Ueland, M. Ebbing, J. E. Nordrehaug, J. Igland, R. Seifert, R. M. Nilsen and O. Nygard: Urinary excretion of kynurenine and tryptophan, cardiovascular events, and mortality after elective coronary angiography. Eur Heart J, 34 (34), 2689-96 (2013)
DOI: 10.1093/eurheartj/eht264

180. V. Rudzite, G. Sileniece, D. Liepina, A. Dalmane and R. Zirne: Impairment of kynurenine metabolism in cardiovascular disease. Adv Exp Med Biol, 294, 663-7 (1991)
DOI: 10.1007/978-1-4684-5952-4_89

181. B. Frick, K. Schroecksnadel, G. Neurauter, F. Leblhuber and D. Fuchs: Increasing production of homocysteine and neopterin and degradation of tryptophan with older age. Clin Biochem, 37 (8), 684-7 (2004)
DOI: 10.1016/j.clinbiochem.2004.02.007

182. M. Pertovaara, A. Raitala, T. Lehtimaki, P. J. Karhunen, S. S. Oja, M. Jylha, A. Hervonen and M. Hurme: Indoleamine 2,3-dioxygenase activity in nonagenarians is markedly increased and predicts mortality. Mech Ageing Dev, 127 (5), 497-9 (2006)
DOI: 10.1016/j.mad.2006.01.020

183. G. Brandacher, C. Winkler, F. Aigner, H. Schwelberger, K. Schroecksnadel, R. Margreiter, D. Fuchs and H. G. Weiss: Bariatric surgery cannot prevent tryptophan depletion due to chronic immune activation in morbidly obese patients. Obes Surg, 16 (5), 541-8 (2006)
DOI: 10.1381/096089206776945066

184. M. Pertovaara, A. Raitala, M. Juonala, T. Lehtimaki, H. Huhtala, S. S. Oja, E. Jokinen, J. S. Viikari, O. T. Raitakari and M. Hurme: Indoleamine 2,3-dioxygenase enzyme activity correlates with risk factors for atherosclerosis: the Cardiovascular Risk in Young Finns Study. Clin Exp Immunol, 148 (1), 106-11 (2007)
DOI: 10.1111/j.1365-2249.2007.03325.x

185. P. Niinisalo, N. Oksala, M. Levula, M. Pelto-Huikko, O. Jarvinen, J. P. Salenius, L. Kytomaki, J. T. Soini, M. Kahonen, R. Laaksonen, M. Hurme and T. Lehtimaki: Activation of indoleamine 2,3-dioxygenase-induced tryptophan degradation in advanced atherosclerotic plaques: Tampere vascular study. Ann Med, 42 (1), 55-63 (2010)
DOI: 10.3109/07853890903321559

186. B. Wirleitner, V. Rudzite, G. Neurauter, C. Murr, U. Kalnins, A. Erglis, K. Trusinskis and D. Fuchs: Immune activation and degradation of tryptophan in coronary heart disease. Eur J Clin Invest, 33 (7), 550-4 (2003)
DOI: 10.1046/j.1365-2362.2003.01186.x

187. B. Widner, A. Laich, B. Sperner-Unterweger, M. Ledochowski and D. Fuchs: Neopterin production, tryptophan degradation, and mental depression--what is the link? Brain Behav Immun, 16 (5), 590-5 (2002)
DOI: 10.1016/S0889-1591(02) 00006-5

188. G. Sulo, S. E. Vollset, O. Nygard, O. Midttun, P. M. Ueland, S. J. Eussen, E. R. Pedersen and G. S. Tell: Neopterin and kynurenine-tryptophan ratio as predictors of coronary events in older adults, the Hordaland Health Study. Int J Cardiol, 168 (2), 1435-40 (2013)
DOI: 10.1016/j.ijcard.2012.12.090

189. I. T. Daissormont, A. Christ, L. Temmerman, S. Sampedro Millares, T. Seijkens, M. Manca, M. Rousch, M. Poggi, L. Boon, C. van der Loos, M. Daemen, E. Lutgens, B. Halvorsen, P. Aukrust, E. Janssen and E. A. Biessen: Plasmacytoid dendritic cells protect against atherosclerosis by tuning T-cell proliferation and activity. Circ Res, 109 (12), 1387-95 (2011)
DOI: 10.1161/CIRCRESAHA.111.256529

190. K. Nakajima, T. Yamashita, T. Kita, M. Takeda, N. Sasaki, K. Kasahara, M. Shinohara, Y. Rikitake, T. Ishida, M. Yokoyama and K. Hirata: Orally administered eicosapentaenoic acid induces rapid regression of atherosclerosis via modulating the phenotype of dendritic cells in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol, 31 (9), 1963-72 (2011)
DOI: 10.1161/ATVBAHA.111.229443

191. M. Masoumy, J. Yu, J. Y. Liu, N. Yanasak, C. Middleton, F. Lamoke, M. S. Mozaffari and B. Baban: The role of indoleamine 2,3 dioxygenase in beneficial effects of stem cells in hind limb ischemia reperfusion injury. PLoS One, 9 (4), e95720 (2014)
DOI: 10.1371/journal.pone.0095720

192. L. Zhang, O. Ovchinnikova, A. Jonsson, A. M. Lundberg, M. Berg, G. K. Hansson and D. F. Ketelhuth: The tryptophan metabolite 3-hydroxyanthranilic acid lowers plasma lipids and decreases atherosclerosis in hypercholesterolaemic mice. Eur Heart J, 33 (16), 2025-34 (2012)
DOI: 10.1093/eurheartj/ehs175

193. J. C. Schefold, J. P. Zeden, C. Fotopoulou, S. von Haehling, R. Pschowski, D. Hasper, H. D. Volk, C. Schuett and P. Reinke: Increased indoleamine 2,3-dioxygenase (IDO) activity and elevated serum levels of tryptophan catabolites in patients with chronic kidney disease: a possible link between chronic inflammation and uraemic symptoms. Nephrol Dial Transplant, 24 (6), 1901-8 (2009)
DOI: 10.1093/ndt/gfn739

194. K. Pawlak, A. Kowalewska, M. Mysliwiec and D. Pawlak: Kynurenine and its metabolites--kynurenic acid and anthranilic acid are associated with soluble endothelial adhesion molecules and oxidative status in patients with chronic kidney disease. Am J Med Sci, 338 (4), 293-300 (2009)
DOI: 10.1097/MAJ.0b013e3181aa30e6

195. K. Pawlak, A. Kowalewska, M. Mysliwiec and D. Pawlak: 3-hydroxyanthranilic acid is independently associated with monocyte chemoattractant protein-1 (CCL2) and macrophage inflammatory protein-1beta (CCL4) in patients with chronic kidney disease. Clin Biochem, 43 (13-14), 1101-6 (2010)

196. K. Pawlak, M. Mysliwiec and D. Pawlak: Kynurenine pathway - a new link between endothelial dysfunction and carotid atherosclerosis in chronic kidney disease patients. Adv Med Sci, 55 (2), 196-203 (2010)
DOI: 10.2478/v10039-010-0015-6

197. A. Zinellu, S. Sotgia, A. A. Mangoni, M. Sanna, A. E. Satta and C. Carru: Impact of cholesterol lowering treatment on plasma kynurenine and tryptophan concentrations in chronic kidney disease: Relationship with oxidative stress improvement. Nutr Metab Cardiovasc Dis (2014)

198. K. Pawlak, B. Naumnik, S. Brzosko, D. Pawlak and M. Mysliwiec: Oxidative stress - a link between endothelial injury, coagulation activation, and atherosclerosis in haemodialysis patients. Am J Nephrol, 24 (1), 154-61 (2004)
DOI: 10.1159/000076244

199. K. Pawlak, T. Domaniewski, M. Mysliwiec and D. Pawlak: Kynurenines and oxidative status are independently associated with thrombomodulin and von Willebrand factor levels in patients with end-stage renal disease. Thromb Res, 124 (4), 452-7 (2009)
DOI: 10.1016/j.thromres.2009.04.011

200. K. Pawlak, T. Domaniewski, M. Mysliwiec and D. Pawlak: The kynurenines are associated with oxidative stress, inflammation and the prevalence of cardiovascular disease in patients with end-stage renal disease. Atherosclerosis, 204 (1), 309-14 (2009)
DOI: 10.1016/j.atherosclerosis.2008.08.014

201. K. Pawlak, A. Buraczewska-Buczko, M. Mysliwiec and D. Pawlak: Hyperfibrinolysis, uPA/suPAR system, kynurenines, and the prevalence of cardiovascular disease in patients with chronic renal failure on conservative treatment. Am J Med Sci, 339 (1), 5-9 (2010)
DOI: 10.1097/MAJ.0b013e3181b922a4

202. K. Pawlak, J. Tankiewicz, M. Mysliwiec and D. Pawlak: Systemic levels of MMP2/TIMP2 and cardiovascular risk in CAPD patients. Nephron Clin Pract, 115 (4), c251-8 (2010)

203. K. Pawlak, S. Brzosko, M. Mysliwiec and D. Pawlak: Kynurenine, quinolinic acid--the new factors linked to carotid atherosclerosis in patients with end-stage renal disease. Atherosclerosis, 204 (2), 561-6 (2009)
DOI: 10.1016/j.atherosclerosis.2008.10.002

204. A. Kato, Y. Suzuki, T. Suda, M. Suzuki, M. Fujie, T. Takita, M. Furuhashi, Y. Maruyama, K.Chida and A. Hishida: Relationship between an increased serum kynurenine/tryptophan ratio and atherosclerotic parameters in hemodialysis patients. Hemodial Int, 14 (4), 418-24 (2010)
DOI: 10.1111/j.1542-4758.2010.00464.x

205. T. Eleftheriadis, G. Antoniadi, V. Liakopoulos, I. Stefanidis and G. Galaktidou: Plasma indoleamine 2,3-dioxygenase concentration is increased in hemodialysis patients and may contribute to the pathogenesis of coronary heart disease. Ren Fail, 34 (1), 68-72 (2012)
DOI: 10.3109/0886022X.2011.623562

206. A. R. Folsom, N. Aleksic, E. Park, V. Salomaa, H. Juneja and K. K. Wu: Prospective study of fibrinolytic factors and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb Vasc Biol, 21 (4), 611-7 (2001)
DOI: 10.1161/01.ATV.21.4.611

207. M. P. Vincenti: The matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) genes. Transcriptional and posttranscriptional regulation, signal transduction and cell-type-specific expression. Methods Mol Biol, 151, 121-48 (2001)

208. K. Schroecksnadel, C. Winkler, C. Duftner, B. Wirleitner, M. Schirmer and D. Fuchs: Tryptophan degradation increases with stage in patients with rheumatoid arthritis. Clin Rheumatol, 25 (3), 334-7 (2006)
DOI: 10.1007/s10067-005-0056-6

209. R. Huttunen, J. Syrjanen, J. Aittoniemi, S. S. Oja, A. Raitala, J. Laine, M. Pertovaara, R. Vuento, H. Huhtala and M. Hurme: High activity of indoleamine 2,3 dioxygenase enzyme predicts disease severity and case fatality in bacteremic patients. Shock, 33 (2), 149-54 (2010)
DOI: 10.1097/SHK.0b013e3181ad3195

210. I. D. Jung, M. G. Lee, J. H. Chang, J. S. Lee, Y. I. Jeong, C. M. Lee, W. S. Park, J. Han, S. K. Seo, S. Y. Lee and Y. M. Park: Blockade of indoleamine 2,3-dioxygenase protects mice against lipopolysaccharide-induced endotoxin shock. J Immunol, 182 (5), 3146-54 (2009)
DOI: 10.4049/jimmunol.0803104

211. F. Bari, K. Nagy, P. Guidetti, R. Schwarcz, D. W. Busija and F. Domoki: Kynurenic acid attenuates NMDA-induced pial arteriolar dilation in newborn pigs. Brain Res, 1069 (1), 39-46 (2006)
DOI: 10.1016/j.brainres.2005.11.033

212. O. Midttun, A. Ulvik, E. Ringdal Pedersen, M. Ebbing, O. Bleie, H. Schartum-Hansen, R. M. Nilsen, O. Nygard and P. M. Ueland: Low plasma vitamin B-6 status affects metabolism through the kynurenine pathway in cardiovascular patients with systemic inflammation. J Nutr, 141 (4), 611-7 (2011)
DOI: 10.3945/jn.110.133082

213. A. Amann, B. Widner, J. Rieder, H. Antretter, G. Hoffmann, V. Mayr, H. U. Strohmenger and D. Fuchs: Monitoring of immune activation using biochemical changes in a porcine model of cardiac arrest. Mediators Inflamm, 10 (6), 343-6 (2001)
DOI: 10.1080/09629350120102370

214. G. Ristagno, M. Fries, L. Brunelli, F. Fumagalli, R. Bagnati, I. Russo, L. Staszewsky, S. Masson, G. Li Volti, A. Zappala, M. Derwall, A. Brucken, R. Pastorelli and R. Latini: Early kynurenine pathway activation following cardiac arrest in rats, pigs, and humans. Resuscitation, 84 (11), 1604-10 (2013)
DOI: 10.1016/j.resuscitation.2013.06.002

215. M. Hoshi, K. Matsumoto, H. Ito, H. Ohtaki, Y. Arioka, Y. Osawa, Y. Yamamoto, H. Matsunami, A. Hara, M. Seishima and K. Saito: L-tryptophan-kynurenine pathway metabolites regulate type I IFNs of acute viral myocarditis in mice. J Immunol, 188 (8), 3980-7 (2012)
DOI: 10.4049/jimmunol.1100997

216. M. Hoshi, K. Saito, A. Hara, A. Taguchi, H. Ohtaki, R. Tanaka, H. Fujigaki, Y. Osawa, M. Takemura, H. Matsunami, H. Ito and M. Seishima: The absence of IDO upregulates type I IFN production, resulting in suppression of viral replication in the retrovirus-infected mouse. J Immunol, 185 (6), 3305-12 (2010)
DOI: 10.4049/jimmunol.0901150

Key Words: Kynurenines, Cardiovascular Diseases, Inflammation, Oxidative Stress, Immune Activation, Review

Send correspondence to: Ming-Hui Zou, Division of Molecular Medicine, Department of Medicine, and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA, Tel: 405-271-3974, Fax: 405-271-3973, E-mail: ming-hui-zou@ouhsc.edu