Skip to main content
SpringerLink
Log in

The relationship between uric acid and its oxidative product allantoin: a potential indicator for the evaluation of oxidative stress in birds

  • Original Paper
  • Published:
Journal of Comparative Physiology B Aims and scope Submit manuscript

Abstract

Uric acid is the main nitrogenous waste product in birds but it is also known to be a potent antioxidant. Hominoid primates and birds lack the enzyme urate oxidase, which oxidizes uric acid to allantoin. Consequently, the presence of allantoin in their plasma results from non-enzymatic oxidation. In humans, the allantoin to uric acid ratio in plasma increases during oxidative stress, thus this ratio has been suggested to be an in vivo marker for oxidative stress in humans. We measured the concentrations of uric acid and allantoin in the plasma and ureteral urine of white-crowned sparrows (Zonotrichia leucophrys gambelii) at rest, immediately after 30 min of exercise in a hop/hover wheel, and after 1 h of recovery. The plasma allantoin concentration and the allantoin to uric acid ratio did not increase during exercise but we found a positive relationship between the concentrations of uric acid and allantoin in the plasma and in the ureteral urine in the three activity phases. In the plasma, the slope of the regression describing the above positive relationships was significantly higher immediately after activity. We suggest that the slope indicates the rate of uric acid oxidation and that during activity this rate increases as a result of higher production of free radicals. The present study demonstrates that allantoin is present in the plasma and in the ureteral urine of white-crowned sparrows and therefore might be useful as an indicator of oxidative stress in birds.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Alderman MH, Cohen H, Madhavan S, Kivlighn S (1999) Serum uric acid and cardiovascular events in successfully treated hypertensive patients. Hypertension 34:144–150

    PubMed  CAS  Google Scholar 

  • Ames BN, Cathcart R, Schwiers E, Hochstein P (1981) Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci 78:6858–6862

    Article  PubMed  CAS  Google Scholar 

  • Barja G (1998) Mitochondrial free radical production and aging in mammals and birds. Ann NY Acad Sci 854:224–238

    Article  PubMed  CAS  Google Scholar 

  • Becker BF (1993) Towards the physiological function of uric acid. Free Radic Biol Med 14:615–631

    Article  PubMed  CAS  Google Scholar 

  • Benzie IFF, Chung W, Tomlinson B (1999) Simultaneous measurement of allantoin and urate in plasma: analytical evaluation and potential clinical application in oxidant: antioxidant balance study. Clin Chem 45:901–904

    PubMed  CAS  Google Scholar 

  • Briggs JP, Levitt MF, Abramson RG (1977) Renal excretion of allantoin in rats: a micropuncture and clearance study. Am J Physiol 233:F373–F381

    PubMed  CAS  Google Scholar 

  • Chappell MA, Bech C, Buttemer WA (1999) The relationship of central and peripheral organ masses to aerobic performance variation in house sparrows. J Exp Biol 202:2269–2279

    PubMed  Google Scholar 

  • Chevion S, Moran DS, Heled Y, Shani Y, Tegev G, Abbou B, Berenshtein E., Stadtman ER, Epstein Y (2003) Plasma antioxidant status and cell injury after severe physical exercise. Proc Natl Acad Sci 100:5119–5123

    Article  PubMed  CAS  Google Scholar 

  • Durken M, Herrnring C, Finckh B, Nagel S, Nielsen P, Fischer R, Berger HM, Moison RM, Pichlmeier U, Kohlschutter B, Zander AR, Kohlschutter A (2000) Impaired plasma antioxidative defense and increased nontransferrin-bound iron during high-dose chemotherapy and radiochemotherapy preceding bone marrow transplantation. Free Radic Biol Med 15:887–894

    Article  Google Scholar 

  • Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH, Hosoyamada M, Takeda M, Sekine T, Igarashi T, Matsuo H, Kikuchi Y, Oda T, Ichida K, Hosoya T, Shimokata K, Niwa T, Kanai Y, Endou H (2002) Molecular identification of a renal urate-anion exchanger that regulates blood urate levels. Nature 417:447–452

    PubMed  CAS  Google Scholar 

  • Gannes LZ, Hatch KA, Pinshow B (2001) How does time since feeding affect the fuels pigeons use during flight? Physiol Biochem Zool 74:1–10

    Article  PubMed  CAS  Google Scholar 

  • George JC, John TM (1993) Flight effects on certain blood parameters in homing pigeons Columba livia. Comp Biochem Physiol 106A:707–712

    Article  CAS  Google Scholar 

  • Giladi I, Goldstein DL, Pinshow B, Gerstberger R (1997) Renal function and plasma levels of arginine vasotocin during free flight in pigeons. J Exp Biol 200:3203–3211

    PubMed  CAS  Google Scholar 

  • Goldstein DL, Braun EJ (1986) Lower intestinal modification of ureteral urine in hydrated house sparrows. Am J Physiol 250:R89–R95

    PubMed  CAS  Google Scholar 

  • Goldstein DL, Skadhauge E (2000) Renal and extrarenal regulation of body fluids. In: Whittow GC (eds) Sturkie’s avian physiology. Academic, New York, pp 265–297

    Chapter  Google Scholar 

  • Grootveld M, Halliwell B (1987) Measurement of allantoin and uric acid in human body fluids. A potential index of free-radical reactions in vivo? Biochem J 243:803–808

    PubMed  CAS  Google Scholar 

  • Hediger MA (2002) Gateway to a long life? Nature 417:393–395

    Article  PubMed  CAS  Google Scholar 

  • Hellsten Y, Tullson PC, Pichter EA, Bangsbo J (1997) Oxidation of urate in human skeletal muscle during exercise. Free Radic Biol Med 22:169–174

    Article  PubMed  CAS  Google Scholar 

  • Hellsten Y, Richter A, Kiens B, Bangsbo J (1999) AMP deamination and purine exchange in human skeletal muscle during and after intense exercise. J Physiol 520:909–920

    Article  PubMed  CAS  Google Scholar 

  • Hellsten Y, Svensson M, Sjödin B, Smith S, Christensen A, Richter EA, Bangsbo J (2001) Allantoin formation and urate glutathione exchange in human muscle during submaximal exercise. Free Radic Biol Med 31:1313–1322

    Article  PubMed  CAS  Google Scholar 

  • Hellsten-Westing Y, Kaijser L, Ekblom B, Sjödin B (1994) Exchange of purines in human liver and skeletal muscle with short term exhaustive exercise. Am J Physiol 266:R81–R86

    PubMed  CAS  Google Scholar 

  • Herrero A, Barja G (1997) Sites and mechanisms responsible for the low rate of free radical production of heart mitochondria in the long-lived pigeon. Mech Ageing Dev 98:95–111

    Article  PubMed  CAS  Google Scholar 

  • Iqbal M, Probert LL, Alhumadi ND, Klandorf H (1999) Protein glycosylation and advanced glycosylated endproducts (AGEs) accumulation: an avian solution? J Gerontol 54A:B171–B176

    CAS  Google Scholar 

  • James TJ, Hughes MA, Cherry GW, Taylor RP (2003) Evidence of oxidative stress in chronic venous ulcers. Wound Repair Regen 11:172–176

    Article  PubMed  Google Scholar 

  • Jenni-Eiermann S, Jenni L (1991) Metabolic responses to flight and fasting in night-migrating passerines. J Comp Physiol B 161:465–474

    Article  Google Scholar 

  • Jenni-Eiermann S, Jenni L, Kvist A, Lindström Å, Piersma T, Visser GH (2002) Fuel use and metabolic response to endurance exercise: a wind tunnel study of a long-distance migrant shorebird. J Exp Biol 205:2453–2460

    PubMed  Google Scholar 

  • Ji LL (1999) Antioxidant and oxidative stress in exercise. Proc Soc Exp Biol Med 222:283–292

    Article  PubMed  CAS  Google Scholar 

  • Kaur H, Halliwell B (1990) Action of biologically-relevant oxidizing species upon uric acid. Identification of uric acid oxidation products. Chem Biol Interact 73:235–247

    Article  PubMed  CAS  Google Scholar 

  • Kirschbaum B (2001) Renal regulation of plasma total antioxidant capacity. Med Hypotheses 56:625–629

    Article  PubMed  CAS  Google Scholar 

  • Klaassen M, Kvist A, Lindström A (2000) Flight costs and fuel composition of a bird migrating in a wind tunnel. Condor 102:444–451

    Article  Google Scholar 

  • Klandorf H, Probert LL, Iqbal M (1999) In the defense against hyperglycaemia: an avian strategy. World’s Poult Sci J 55:251–268

    Article  Google Scholar 

  • Klandorf H, Rathore DS, Iqbal M, Shi X, Van Dyke K (2001) Accelerating tissue aging and increased oxidative stress in broiler chickens fed allopurinol. Comp Biochem Physiol 129C:93–104

    CAS  Google Scholar 

  • Lagendijk J, Ubbink JB, Hayward Vermaak WJ (1995) The determination of allantoin, a possible indicator of oxidant status, in human plasma. J Chromatogr Sci 33:186–193

    PubMed  CAS  Google Scholar 

  • Lin H, Decuypere E, Buyse J (2004) Oxidative stress induced by corticosterone administration in broiler chickens (Gallus gallus domesticus) 2. Short-term effect. Comp Biochem Physiol 139B:745–751

    CAS  Google Scholar 

  • Liu ML, Bergholm R, Mäkimattila S, Lahdenperä S, Valkonen M, Hilden H, Yki-Järvinen H, Taskinen MR (1999) A marathon run increases the susceptibility of LDL to oxidation in vitro and modifies plasma antioxidants. Am J Physiol 276:E1083–E1091

    PubMed  CAS  Google Scholar 

  • Lumeij TJ, Remple JD (1991) Plasma urea, creatinine and uric acid concentrations in relation to feeding in peregrine falcons (Falco peregrinus). Avian Pathol 20:79–83

    Article  CAS  Google Scholar 

  • Machín M, Simoyi MF, Blemings KP, Klandorf H (2004) Increased dietary protein elevates plasma uric acid and is associated with decreased oxidative stress in rapidly-growing broilers. Comp Biochem Physiol B 137:383–390

    Article  PubMed  Google Scholar 

  • Marklund N, Ostman B, Nalmo L, Persson L, Hillered L (2000) Hypoxanthine, uric acid and allantoin as indicators of in vivo free radical reactions. Description of a HPLC method and human brain microdialysis data. Acta Neurochir (Wien) 142:1135–1142

    Article  CAS  Google Scholar 

  • Mastaloudis A, Leonard SC, Traber MG (2001) Oxidation stress in athletes during extreme endurance exercise. Free Radic Biol Med 31:911–922

    Article  PubMed  CAS  Google Scholar 

  • Mikami T, Yoshino Y, Ito A (2000a) Does a relationship exist between the urate pool in the body and lipid peroxidation during exercise? Free Radic Res 32:31–39

    Article  CAS  Google Scholar 

  • Mikami T, Kita K, Tomita S, Qu GJ, Tasaki Y, Ito A (2000b) Is allantoin in serum and urine a useful indicator of exercise-induced oxidative stress in humans? Free Radic Res 32:235–244

    Article  CAS  Google Scholar 

  • Moriwaki Y, Yamamoto T, Higashino K (1999) Enzymes involved in purine metabolism—a review of histochemical localization and functional implications. Histol Histopathol 14:1321–1340

    PubMed  CAS  Google Scholar 

  • Muradian KK, Utko NA, Mozzhukhina TG, Litoshenko AY, Pishel IN, Bezrukov VV, Fraifield VE (2002) Pair-wise linear and 3D nonlinear relationships between the liver antioxidant enzyme activities and the rate of body oxygen consumption in mice. Free Radic Biol Med 33:1736–1739

    Article  PubMed  CAS  Google Scholar 

  • Oda M, Satta Y, Takenaka O, Takahata N (2002) Loss of urate oxidase activity in hominoids and its evolutionary implication. Mol Biol Evol 19:640–653

    PubMed  CAS  Google Scholar 

  • Ogihara T, Kim H, Hirano K, Imanish M, Ogihara H, Tamai H, Okamoio R, Mino M (1998) Oxidation products of uric acid and ascorbic acid in preterm infants with chronic lung disease. Biol Neonate 73:24–33

    Article  PubMed  CAS  Google Scholar 

  • Poffers J, Lumeij TJ, Redig PT (2002) Investigations into the uricotelic properties of urate oxidase in a granivorous (Columba livia domestica) and in a carnivorous (Buteo jamaicensis) avian species. Avian Pathol 31:573–579

    Article  PubMed  CAS  Google Scholar 

  • Pösö AR, Nieminen M, Sankari S, Soveri T (1994) Exercise-induced changes in blood composition of racing reindeer (Rangifer tarandus tarandus L.). Am J Physiol 267:R1209–R1216

    PubMed  Google Scholar 

  • Räsänen LA, Lampinen KL, Pösö AR (1995) Responses of blood and plasma lactate and plasma purine concentrations to maximal exercise and their relation to performance in Standardbred trotters. Am J Vet Res 56:1651–1656

    PubMed  Google Scholar 

  • Roxburgh L, Pinshow B (2002) Ammonotely in a passerine nectarivore: the influence of renal and post-renal modification on nitrogenous waste product excretion. J Exp Biol 205:1735–1745

    PubMed  Google Scholar 

  • Sato A, Nishino T, Noda K, Amaya Y, Nishino T (1995) The structure of chicken liver xanthine dehydrogenase. cDNA cloning and the domain structure. J Biol Chem 270:2818–2826

    Article  PubMed  CAS  Google Scholar 

  • Shmueli M, Izhaki I, Zinder O, Arad Z (2000) The physiological state of captive and migrating Great White Pelicans (Pelecanus onocrotalus) revealed by their blood chemistry. Comp Biochem Physiol 125A:25–32

    CAS  Google Scholar 

  • Simic MG, Jovanovic SV (1989) Antioxidation mechanisms of uric acid. J Am Chem Soc 111:5778–5782

    Article  CAS  Google Scholar 

  • Simoyi MF, van Dyke K, Klandorf H (2002) Manipulation of plasma uric acid in broiler chicks and its effect on leukocyte oxidative activity. Am J Physiol 282:R791–R796

    CAS  Google Scholar 

  • Simoyi MF, Falkenstain E, Van Dyke K, Blemings KP, Klandorf H (2003) Allantoin, the oxidation product of uric acid is present in chicken and turkey plasma. Comp Biochem Physiol 135B:325–335

    CAS  Google Scholar 

  • Stinefelt B, Leonard SS, Bleming KP, Shi X, Klandorf H (2005) Free radical scavenging, DNA protection, and inhibition of lipid peroxidation mediated by uric acid. Ann Clin Lab Sci 35:37–45

    PubMed  CAS  Google Scholar 

  • Tsahar E, Martínez del Rio C, Arad Z, Joy JP, Izhaki I (2005) Are the low protein requirements of nectarivorous birds the consequence of their sugary and watery diet?—a test with an omnivore. Physiol Biochem Zool 78:239–245

    Article  PubMed  Google Scholar 

  • Wright PA (1995) Nitrogen excretion: three end products, many physiological roles. J Exp Biol 198:273–281

    PubMed  CAS  Google Scholar 

  • Wetzstein CJ, Shern-Brewer RA, Santanam N, Green NR, White-Welkley LE, Parthasarathy S (1998) Does acute exercise affects the susceptibility of low density lipoprotein to oxidation? Free Radical Biol Med 24:679–682

    Article  CAS  Google Scholar 

  • Yardim-Akaydin S, Sepici A, Ozkan Y, Torun M, Simsek B, Sepici V (2004) Oxidation of uric acid in rheumatoid arthritis: is allantoin a marker of oxidative stress? Free Radical Res 38:623–628

    Article  CAS  Google Scholar 

  • Young EG, Conway CF (1942) On the estimation of allantoin by the Rimini-Schryver reaction. J Biol Chem 142:839–853

    CAS  Google Scholar 

  • Zitnanova I, Korytar P, Aruoma OI, Sustrova M, Garaiova I, Muchova J, Kalnovicova T, Pueschel S, Durackova Z (2004) Uric acid and allantoin levels in Down syndrome: antioxidant and oxidative stress mechanisms? Clin Chem Acta 341:139–146

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We wish to thank Prof. Carlos Martínez del-Rio for his help and involvement throughout the study including his advices in the manuscript preparation and his help in the statistical analysis. Also thanks to Edwin Price, Quentin Hays, David Cerasale for their assistance in catching and maintaining the birds and in blood sampling, and for their kind hospitality, and Bradley H. Bakken for his assistance in analyzing the samples. We also thank three anonymous reviewers whose comments greatly improved this manuscript. The study was partially financed by grants to C. Martínez del-Rio (NSF IBN-0110416) and to C.G. Guglielmo (NSF IBN-0224954), by the Technion’s J. and A. Taub Biological Research Fund and J. S. Frankford Research Fund (to Zeev Arad), and by the Technion-University of Haifa Interuniversity Research Fund (to Zeev Arad and Ido Izhaki).

Author information

Author notes

  1. Christopher G. Guglielmo

    Present address: Department of Biology, University of Western Ontario, London, ON, Canada, N6A 5B7

Authors and Affiliations

  1. Department of Biology, Technion—Israel Institute of Technology, Haifa, 32000, Israel

    Ella Tsahar & Zeev Arad

  2. Department of Biology, University of Haifa at Oranim, K. Tivon, 36006, Israel

    Ido Izhaki

  3. Division of Biological Sciences, University of Montana, Missoula, MT, 59802, USA

    Christopher G. Guglielmo

Authors
  1. Ella Tsahar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zeev Arad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ido Izhaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christopher G. Guglielmo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ella Tsahar.

Additional information

Communicated by I.D. Hume

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsahar, E., Arad, Z., Izhaki, I. et al. The relationship between uric acid and its oxidative product allantoin: a potential indicator for the evaluation of oxidative stress in birds. J Comp Physiol B 176, 653–661 (2006). https://doi.org/10.1007/s00360-006-0088-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00360-006-0088-5

Keywords

Search

Navigation