Efficacy of Para-Tyrosine Supplementation on the Survival and Clinical Outcome in Patients With Sepsis

Summary

Meta-and ortho-Tyrosine are known markers of oxidative stress, while the physiological isomer, para-Tyrosine is suggested the antagonize the effects of meta- and ortho-Tyrosine. The changes in the serum levels of meta- and ortho-Tyrosine have been found to be paralel to that of the common sepsis markers. The hypothesis of the study is, that supplementation of para-Tyrosine (p-Tyr) in the early phase of sepsis may diminish some specific inflammatory procedures and thus may have a favourable impact on the disease progress, and consequently on the mortality.

Timeline

Start

2027-01

Primary completion

2027-01-01

Completion

2027-02-28

Outcome

Outcome not reported

Stopped: “Lack of resources to start”

Publications

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• Background Kun S, Mikolas E, Molnar GA, Selley E, Laczy B, Csiky B, Kovacs T, Wittmann I. Association of plasma ortho-tyrosine/para-tyrosine ratio with responsiveness of erythropoiesis-stimulating agent in dialyzed patients. Redox Rep. 2014 Sep;19(5):190-8. doi: 10.1179/1351000214Y.0000000090. Epub 2014 Apr 3.
• Background Kun S, Molnar GA, Selley E, Szelig L, Bogar L, Csontos C, Miseta A, Wittmann I. Insulin Therapy of Nondiabetic Septic Patients Is Predicted by para-Tyrosine/Phenylalanine Ratio and by Hydroxyl Radical-Derived Products of Phenylalanine. Oxid Med Cell Longev. 2015;2015:839748. doi: 10.1155/2015/839748. Epub 2015 Oct 20.
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• Background Lubec B, Hayn M, Denk W, Bauer G. Brain lipid peroxidation and hydroxy radical attack following the intravenous infusion of hydrogen peroxide in an infant. Free Radic Biol Med. 1996;21(2):219-23. doi: 10.1016/0891-5849(96)00018-4.
• Background Mikolas E, Kun S, Laczy B, Molnar GA, Selley E, Koszegi T, Wittmann I. Incorporation of ortho- and meta-tyrosine into cellular proteins leads to erythropoietin-resistance in an erythroid cell line. Kidney Blood Press Res. 2013;38(2-3):217-25. doi: 10.1159/000355770. Epub 2014 Apr 9.
• Background Molnar GA, Nemes V, Biro Z, Ludany A, Wagner Z, Wittmann I. Accumulation of the hydroxyl free radical markers meta-, ortho-tyrosine and DOPA in cataractous lenses is accompanied by a lower protein and phenylalanine content of the water-soluble phase. Free Radic Res. 2005 Dec;39(12):1359-66. doi: 10.1080/10715760500307107.
• Background Molnar GA, Wagner Z, Marko L, Ko Szegi T, Mohas M, Kocsis B, Matus Z, Wagner L, Tamasko M, Mazak I, Laczy B, Nagy J, Wittmann I. Urinary ortho-tyrosine excretion in diabetes mellitus and renal failure: evidence for hydroxyl radical production. Kidney Int. 2005 Nov;68(5):2281-7. doi: 10.1111/j.1523-1755.2005.00687.x.
• Background Szijarto IA, Molnar GA, Mikolas E, Fisi V, Cseh J, Laczy B, Kovacs T, Boddi K, Takatsy A, Gollasch M, Koller A, Wittmann I. Elevated vascular level of ortho-tyrosine contributes to the impairment of insulin-induced arterial relaxation. Horm Metab Res. 2014 Oct;46(11):749-52. doi: 10.1055/s-0034-1387701. Epub 2014 Sep 10.
• Background Molnar GA, Mikolas EZ, Szijarto IA, Kun S, Selley E, Wittmann I. Tyrosine isomers and hormonal signaling: A possible role for the hydroxyl free radical in insulin resistance. World J Diabetes. 2015 Apr 15;6(3):500-7. doi: 10.4239/wjd.v6.i3.500.
• Background Molnar GA, Kun S, Selley E, Kertesz M, Szelig L, Csontos C, Boddi K, Bogar L, Miseta A, Wittmann I. Role of Tyrosine Isomers in Acute and Chronic Diseases Leading to Oxidative Stress - A Review. Curr Med Chem. 2016;23(7):667-85. doi: 10.2174/0929867323666160119094516.
• Background Pandharipande PP, Morandi A, Adams JR, Girard TD, Thompson JL, Shintani AK, Ely EW. Plasma tryptophan and tyrosine levels are independent risk factors for delirium in critically ill patients. Intensive Care Med. 2009 Nov;35(11):1886-92. doi: 10.1007/s00134-009-1573-6. Epub 2009 Jul 9.
• Background Ruggiero RA, Bruzzo J, Chiarella P, di Gianni P, Isturiz MA, Linskens S, Speziale N, Meiss RP, Bustuoabad OD, Pasqualini CD. Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance. Cancer Res. 2011 Nov 15;71(22):7113-24. doi: 10.1158/0008-5472.CAN-11-0581.
• Background Ruggiero RA, Bruzzo J, Chiarella P, Bustuoabad OD, Meiss RP, Pasqualini CD. Concomitant tumor resistance: the role of tyrosine isomers in the mechanisms of metastases control. Cancer Res. 2012 Mar 1;72(5):1043-50. doi: 10.1158/0008-5472.CAN-11-2964. Epub 2012 Feb 7.
• Background Shaw JH, Wildbore M, Wolfe RR. Whole body protein kinetics in severely septic patients. The response to glucose infusion and total parenteral nutrition. Ann Surg. 1987 Mar;205(3):288-94. doi: 10.1097/00000658-198703000-00012.
• Background Selley E, Kun S, Kurthy M, Kovacs T, Wittmann I, Molnar GA. Para-Tyrosine Supplementation Improves Insulin- and Liraglutide- Induced Vasorelaxation in Cholesterol-Fed Rats. Protein Pept Lett. 2015;22(8):736-42. doi: 10.2174/0929866522666150610093039.

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