Prooxidant-antioxidant balance in patients with phenylketonuria and its correlation to biochemical and hematological parameters
-
Somayeh Tavana
und
Asadollah Fathollahpour
Abstract
Background: The balance between reactive oxygen species production and antioxidant activity has an important role in oxidative stress associated diseases such as phenylketonuria (PKU). We aimed in this study to evaluate the possible association between oxidative balance and clinical features of PKU patients.
Methods: Twenty patients and 50 healthy subjects were selected. Prooxidant-antioxidant balance (PAB) was measured and phenylalanine (Phe), tyrosine (Tyr), Phe/Tyr ratio and hematological indices were determined.
Results: A significantly higher PAB value was observed in the patient group (152.0±14.1 HK unit) compared to the controls (88.1±13.88 HK) (p<0.05). There was significant correlation between PAB with serum Phe, Tyr, Phe/Tyr ratio, white blood cells (WBC) and red blood cells (RBC) counts.
Conclusions: The serum PAB values were higher in patients with PKU and this was associated with the serum Phe and Tyr and Phe/Tyr ratio. Therefore, because of its low cost and simplicity to perform, PAB value might be considered as a useful monitoring marker among the other tools in these patients.
Acknowledgments
The author wish to thank all patients and health stuffs who participated in this study. Financial support from Kurdistan University of Medical Sciences is highly appreciated.
Author contributions: S. Tavan: Data collection; S. Amini: Project development; M.S. Hakhamneshi: Data collection; P. Andalibi: Data collection; M.S. Hajir: Data collection; A. Ardalan: Data collection; M. Abdi: Project development data management, data analysis, manuscript writing; A. Fathollahpour: Project development, manuscript editing. All the authors have accepted responsibility for the entire content of the submitted manuscript and approved submission.
Research funding: This work was supported by a research grant from Kurdistan University of medical sciences (Grant/Award Number: ‘45957’).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Greene CL, Longo N. National Institutes of Health (NIH) review of evidence in phenylalanine hydroxylase deficiency (phenylketonuria) and recommendations/guidelines for therapy from the American College of Medical Genetics (ACMG) and Genetics Metabolic Dietitians International (GMDI). Mol Genet Metab 2014;112:85–6.10.1016/j.ymgme.2014.03.005Suche in Google Scholar PubMed
2. Vockley J, Andersson HC, Antshel KM, Braverman NE, Burton BK, et al. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med 2014;16:188–200.10.1038/gim.2013.157Suche in Google Scholar PubMed
3. Lee PJ, Amos A, Robertson L, Fitzgerald B, Hoskin R, et al. Adults with late diagnosed PKU and severe challenging behaviour: a randomised placebo-controlled trial of a phenylalanine-restricted diet. J Neurol Neurosurg Psychiatry 2009;80:631–5.10.1136/jnnp.2008.151175Suche in Google Scholar PubMed
4. Araujo GC, Christ SE, Grange DK, Steiner RD, Coleman C, et al. Executive response monitoring and inhibitory control in children with phenylketonuria: effects of expectancy. Dev Neuropsychol 2013;38:139–52.10.1080/87565641.2012.718816Suche in Google Scholar PubMed
5. de Groot MJ, Hoeksma M, Blau N, Reijngoud DJ, van Spronsen FJ. Pathogenesis of cognitive dysfunction in phenylketonuria: review of hypotheses. Mol Genet Metab 2010;99(Suppl 1):S86–9.10.1016/j.ymgme.2009.10.016Suche in Google Scholar PubMed
6. Stojiljkovic M, Klaassen K, Djordjevic M, Sarajlija A, Kecman B, et al. Tetrahydrobiopterin deficiency among Serbian patients presenting with hyperphenylalaninemia. J Pediatr Endocrinol Metab 2015;28:477–80.10.1515/jpem-2014-0297Suche in Google Scholar PubMed
7. Sutivijit Y, Banpavichit A, Wiwanitkit V. Prevalence of neonatal hypothyroidism and phenylketonuria in Southern Thailand: a 10-year report. Indian J Endocrinol Metab 2011;15:115–7.10.4103/2230-8210.81941Suche in Google Scholar PubMed PubMed Central
8. Guldberg P, Henriksen KF, Sipila I, Guttler F, de la Chapelle A. Phenylketonuria in a low incidence population: molecular characterisation of mutations in Finland. J Med Genet 1995;32:976–8.10.1136/jmg.32.12.976Suche in Google Scholar PubMed PubMed Central
9. Prochazkova D, Jarkovsky J, Hankova Z, Konecna P, Benakova H, et al. Long-term treatment for hyperphenylalaninemia and phenylketonuria: a risk for nutritional vitamin B12 deficiency? J Pediatr Endocrinol Metab 2015;28:1327–32.10.1515/jpem-2014-0489Suche in Google Scholar PubMed
10. Bernstein LE, Helm JR, Rocha JC, Almeida MF, Feillet F, et al. Nutrition education tools used in phenylketonuria: clinician, parent and patient perspectives from three international surveys. J Hum Nutr Diet 2014;27(Suppl 2):4–11.10.1111/jhn.12065Suche in Google Scholar PubMed
11. Enns GM, Koch R, Brumm V, Blakely E, Suter R, et al. Suboptimal outcomes in patients with PKU treated early with diet alone: revisiting the evidence. Mol Genet Metab 2010;101:99–109.10.1016/j.ymgme.2010.05.017Suche in Google Scholar PubMed
12. He Y, Gu X, Lu L, Liang L, Gao J, et al. NOX, the main regulator in oxidative stress in experimental models of phenylketonuria? J Pediatr Endocrinol Metab 2013;26:675–82.10.1515/jpem-2012-0387Suche in Google Scholar PubMed
13. Feillet F, Agostoni C. Nutritional issues in treating phenylketonuria. J Inherit Metab Dis 2010;33:659–64.10.1007/s10545-010-9043-4Suche in Google Scholar PubMed
14. Sirtori LR, Dutra-Filho CS, Fitarelli D, Sitta A, Haeser A, et al. Oxidative stress in patients with phenylketonuria. Biochim Biophys Acta 2005;1740:68–73.10.1016/j.bbadis.2005.02.005Suche in Google Scholar PubMed
15. Sitta A, Barschak AG, Deon M, de Mari JF, Barden AT, et al. L-carnitine blood levels and oxidative stress in treated phenylketonuric patients. Cell Mol Neurobiol 2009;29:211–8.10.1007/s10571-008-9313-ySuche in Google Scholar PubMed
16. Rocha JC, Martins MJ. Oxidative stress in phenylketonuria: future directions. J Inherit Metab Dis 2012;35:381–98.10.1007/s10545-011-9417-2Suche in Google Scholar PubMed
17. Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem 2006;97:1634–58.10.1111/j.1471-4159.2006.03907.xSuche in Google Scholar PubMed
18. Cobb CA, Cole MP. Oxidative and nitrative stress in neurodegeneration. Neurobiol Dis 2015;84:4–21.10.1016/j.nbd.2015.04.020Suche in Google Scholar PubMed PubMed Central
19. Sitta A, Barschak AG, Deon M, Terroso T, Pires R, et al. Investigation of oxidative stress parameters in treated phenylketonuric patients. Metab Brain Dis 2006;21:287–96.10.1007/s11011-006-9035-0Suche in Google Scholar PubMed
20. Sitta A, Manfredini V, Biasi L, Tremea R, Schwartz IV, et al. Evidence that DNA damage is associated to phenylalanine blood levels in leukocytes from phenylketonuric patients. Mutat Res 2009;679:13–6.10.1016/j.mrgentox.2009.07.013Suche in Google Scholar PubMed
21. Sanayama Y, Nagasaka H, Takayanagi M, Ohura T, Sakamoto O, et al. Experimental evidence that phenylalanine is strongly associated to oxidative stress in adolescents and adults with phenylketonuria. Mol Genet Metab 2011;103:220–5.10.1016/j.ymgme.2011.03.019Suche in Google Scholar PubMed
22. Sitta A, Barschak AG, Deon M, Barden AT, Biancini GB, et al. Effect of short- and long-term exposition to high phenylalanine blood levels on oxidative damage in phenylketonuric patients. Int J Dev Neurosci 2009;27:243–7.10.1016/j.ijdevneu.2009.01.001Suche in Google Scholar PubMed
23. Smith I, Knowles J. Behaviour in early treated phenylketonuria: a systematic review. Eur J Pediatr 2000;159(Suppl 2):S89–93.10.1007/PL00014392Suche in Google Scholar
24. Moraes TB, Jacques CE, Rosa AP, Dalazen GR, Terra M, et al. Role of catalase and superoxide dismutase activities on oxidative stress in the brain of a phenylketonuria animal model and the effect of lipoic acid. Cell Mol Neurobiol 2013;33:253–60.10.1007/s10571-012-9892-5Suche in Google Scholar PubMed
25. Moraes TB, Zanin F, da Rosa A, de Oliveira A, Coelho J, et al. Lipoic acid prevents oxidative stress in vitro and in vivo by an acute hyperphenylalaninemia chemically-induced in rat brain. J Neurol Sci 2010;292:89–95.10.1016/j.jns.2010.01.016Suche in Google Scholar PubMed
26. Mazzola PN, Terra M, Rosa AP, Mescka CP, Moraes TB, et al. Regular exercise prevents oxidative stress in the brain of hyperphenylalaninemic rats. Metab Brain Dis 2011;26:291–7.10.1007/s11011-011-9264-8Suche in Google Scholar PubMed
27. Alamdari DH, Paletas K, Pegiou T, Sarigianni M, Befani C, et al. A novel assay for the evaluation of the prooxidant-antioxidant balance, before and after antioxidant vitamin administration in type II diabetes patients. Clin Biochem 2007;40:248–54.10.1016/j.clinbiochem.2006.10.017Suche in Google Scholar PubMed
28. Alamdari DH, Ghayour-Mobarhan M, Tavallaie S, Parizadeh MR, Moohebati M, et al. Prooxidant-antioxidant balance as a new risk factor in patients with angiographically defined coronary artery disease. Clin Biochem 2008;41:375–80.10.1016/j.clinbiochem.2007.12.008Suche in Google Scholar PubMed
29. Blau N, Hennermann JB, Langenbeck U, Lichter-Konecki U. Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies. Mol Genet Metab 2011;104(Suppl):S2–9.10.1016/j.ymgme.2011.08.017Suche in Google Scholar PubMed
30. Gassió R, Artuch R, Vilaseca MA, Fusté E, Colome R, et al. Cognitive functions and the antioxidant system in phenylketonuric patients. Neuropsychology 2008;22:426–31.10.1037/0894-4105.22.4.426Suche in Google Scholar PubMed
31. Martínez-Cruz F, Osuna C, Guerrero JM. Mitochondrial damage induced by fetal hyperphenylalaninemia in the rat brain and liver: its prevention by melatonin, Vitamin E, and Vitamin C. Neurosci Lett 2006;392:1–4.10.1016/j.neulet.2005.02.073Suche in Google Scholar PubMed
32. Ribas GS, Sitta A, Wajner M, Vargas CR. Oxidative stress in phenylketonuria: what is the evidence? Cell Mol Neurobiol 2011;31:653–62.10.1007/s10571-011-9693-2Suche in Google Scholar PubMed
33. Olson H, Betton G, Robinson D, Thomas K, Monro A, et al. Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharm 2000;32:56–67.10.1006/rtph.2000.1399Suche in Google Scholar PubMed
34. Asmah RH, Yeboah G, Asare-Anane H, Antwi-Baffour S, Archampong TN, et al. Relationship between oxidative stress and haematological indices in patients with diabetes in the Ghanaian population. Clin Diabetes Endocrinol 2015;1:1–5.10.1186/s40842-015-0008-2Suche in Google Scholar PubMed PubMed Central
35. Messarah M, Saoudi M, Boumendjel A, Boulakoud MS, Feki AE. Oxidative stress induced by thyroid dysfunction in rat erythrocytes and heart. Environ Toxicol Pharmacol 2011;31:33–41.10.1016/j.etap.2010.09.003Suche in Google Scholar PubMed
36. Beigh SA, Soodan JS, Nazki S, Khan AM. Oxidative stress, hematobiochemical parameters, trace elements and vitamins in dogs with zinc responsive dermatosis. Veterinarski Arhiv 2014;84:591–600.Suche in Google Scholar
37. Preissler T, Bristot IJ, Costa BM, Fernandes EK, Rieger E, et al. Phenylalanine induces oxidative stress and decreases the viability of rat astrocytes: possible relevance for the pathophysiology of neurodegeneration in phenylketonuria. Metab Brain Dis 2015. [Epub ahead of print].10.1007/s11011-015-9763-0Suche in Google Scholar PubMed
©2016 by De Gruyter
Artikel in diesem Heft
- Frontmatter
- Review
- Medullary thyroid carcinoma: a review on ethical considerations in treatment of children
- Original Articles
- Monocyte chemoattractant protein 1 and macrophage migration inhibitory factor in children with type 1 diabetes
- Organ-specific autoimmunity in relation to clinical characteristics in children with long-lasting type 1 diabetes
- Seasonality of diagnosis of type 1 diabetes mellitus in the Netherlands (Young Dudes-2)
- Health-related quality of life in children and adolescents with type 1 diabetes mellitus from Montenegro: relationship to metabolic control
- Relation of fetuin A levels with cardiac, subcutaneous lipid accumulation and insulin resistance parameters in Turkish obese children
- Prooxidant-antioxidant balance in patients with phenylketonuria and its correlation to biochemical and hematological parameters
- Serum vaspin concentrations in girls with anorexia nervosa
- Effect of intramuscular cholecalciferol megadose in children with nutritional rickets
- Focus on BMI and subclinical hypothyroidism in adolescent girls first examined for amenorrhea or oligomenorrhea. The emerging role of polycystic ovary syndrome
- Absence of a relationship between thyroid hormones and vitamin D levels
- Parathyroid hormone-ionized calcium dynamics over the first year of life
- Biochemical markers of bone turnover in children with clinical bone fragility
- Adipocytokines and bone metabolism markers in relation to bone mineral values in early pubertal boys with different physical activity
- Bone mineral density in young Chilean patients with type 1 diabetes mellitus
- Case Reports
- A case of mature teratoma with a falsely high serum estradiol value measured with an immunoassay
- Leigh syndrome associated with a novel mutation in the COX15 gene
- More than one way to skin a thyroid. Managing pediatric hypothyroidism with weekly intramuscular levothyroxine
- First case report of rare congenital adrenal insufficiency caused by mutations in the CYP11A1 gene in the Czech Republic
- Arg924X homozygous mutation in insulin receptor gene in a Tunisian patient with Donohue syndrome
- Corrigendum
- Corrigendum to: Exposure to sunshine early in life prevented development of type 1 diabetes in Danish boys
Artikel in diesem Heft
- Frontmatter
- Review
- Medullary thyroid carcinoma: a review on ethical considerations in treatment of children
- Original Articles
- Monocyte chemoattractant protein 1 and macrophage migration inhibitory factor in children with type 1 diabetes
- Organ-specific autoimmunity in relation to clinical characteristics in children with long-lasting type 1 diabetes
- Seasonality of diagnosis of type 1 diabetes mellitus in the Netherlands (Young Dudes-2)
- Health-related quality of life in children and adolescents with type 1 diabetes mellitus from Montenegro: relationship to metabolic control
- Relation of fetuin A levels with cardiac, subcutaneous lipid accumulation and insulin resistance parameters in Turkish obese children
- Prooxidant-antioxidant balance in patients with phenylketonuria and its correlation to biochemical and hematological parameters
- Serum vaspin concentrations in girls with anorexia nervosa
- Effect of intramuscular cholecalciferol megadose in children with nutritional rickets
- Focus on BMI and subclinical hypothyroidism in adolescent girls first examined for amenorrhea or oligomenorrhea. The emerging role of polycystic ovary syndrome
- Absence of a relationship between thyroid hormones and vitamin D levels
- Parathyroid hormone-ionized calcium dynamics over the first year of life
- Biochemical markers of bone turnover in children with clinical bone fragility
- Adipocytokines and bone metabolism markers in relation to bone mineral values in early pubertal boys with different physical activity
- Bone mineral density in young Chilean patients with type 1 diabetes mellitus
- Case Reports
- A case of mature teratoma with a falsely high serum estradiol value measured with an immunoassay
- Leigh syndrome associated with a novel mutation in the COX15 gene
- More than one way to skin a thyroid. Managing pediatric hypothyroidism with weekly intramuscular levothyroxine
- First case report of rare congenital adrenal insufficiency caused by mutations in the CYP11A1 gene in the Czech Republic
- Arg924X homozygous mutation in insulin receptor gene in a Tunisian patient with Donohue syndrome
- Corrigendum
- Corrigendum to: Exposure to sunshine early in life prevented development of type 1 diabetes in Danish boys
