Thiol/Disulfide Balance in Induced Phenylketonuria Model

Year 2023, Volume: 51 Issue: 3, 309 - 315, 16.07.2023

Çiğdem Çiçek

https://doi.org/10.15671/hjbc.1254604

Abstract

Amaç: Fenilketonüri (PKU), fenilalanin hidroksilaz enzim eksikliği ile karakterize nadir görülen bir kalıtsal metabolik hastalıktır. Bu enzimin eksikliği, kan fenilalanin seviyesini yükselterek, beyinde fenilalanin birikmesine ve geri dönüşümsüz nörolojik hasar oluşmasına neden olur. . Bu çalışmada fenilketonüri modelinde beyin tiyol/disülfit dengesindeki değişimin belirlenmesi amaçlanmıştır.
Yöntem: PKU modeli oluşturulmuş sıçan yavrularında (n:7) ve kontrol grubunda beyin total tiyol ve serbest tiyol seviyesi modifiye elman yöntemi ile ölçüldü. Total tiyol ve native tiyol seviyelerine göre disülfit seviyesi hesaplandı.
Bulgular: PKU grubun beyin total tiyol seviyesi kontrol grubuna göre istatistiksel olarak azdır (*p=0.0369). PKU grubun beyin serbest tiyol seviyesi kontrol grubuna göre istatistiksel olarak azdır (****p<0.001). PKU grubun beyin disülfit seviyesi kontrol grubuna göre istatistiksel olarak değişiklik göstermemiştir (p=0.1107).
Sonuç: PKU’de oluşan oksidatif strese tiyol/disülfit seviyelerininde değişikliklerinde etki edebileceği sonucuna varılmıştır. Literatürde ilk kez rapor edilen çalışmada PKU patofizyolojine tiyol/disülfit dengesininde değişiklik olduğu gösterilmiştir.

Keywords

Fenilketonüri Modeli, Tiyol/Disülfit Dengesi, Oksidatif Stres, Beyin

Project Number

2021/01.003

References

• . Scriber, Hyperphenylalaninemia: phenylalanine hydroxylase deficiency, The metabolic and molecular bases of inherited disease., (2001) 1667-1724.
• N. Blau, Genetics of phenylketonuria: then and now, Human mutation. 37 (2016) 508-515.
• O. Erel and S. Neselioglu, A novel and automated assay for thiol/disulphide homeostasis, Clinical biochemistry., 47 (2014) 326-332.
• P. V. Oliveira and F. R. Laurindo, Implications of plasma thiol redox in disease, Clinical Science. , 132 (2018) 1257-1280.
• A. K. Erenler and T. Yardan, Clinical Utility of Thiol/Disulfide Homeostasis, Clinical laboratory., 63 (2017) 867-870.
• S. Emre, D. D. Demirseren, M. Alisik, A. Aktas, S. Neselioglu, and O. Erel, Dynamic thiol/disulfide homeostasis and effects of smoking on homeostasis parameters in patients with psoriasis, Cutaneous and ocular toxicology., 36 (2017) 393-396.
• B. Elmas, M. Karacan, P. Dervişoğlu, M. Kösecik, Ş. P. İşgüven, and C. Bal, Dynamic thiol/disulphide homeostasis as a novel indicator of oxidative stress in obese children and its relationship with inflammatory-cardiovascular markers, Anatolian journal of cardiology., 18 (2017) 361.
• Z. K. Tufan, I. Hasanoglu, S. Kolgelier, M. Alisik, M. Ergin, G. R. Yilmaz, M. A. Tasyaran, O. Erel, and R. Guner, A retrospective controlled study of thiol disulfide homeostasis as a novel marker in Crimean Congo hemorrhagic fever, Redox Report., 22 (2017) 241-245.
• Z. Wang, W. Zhao, X. Shen, H. Wan, and J. M. Yu, The role of P2Y6 receptors in the maintenance of neuropathic pain and its improvement of oxidative stress in rats, Journal of cellular biochemistry., 120 (2019) 17123-17130.
• A. Horst, J. de Souza, M. Santos, A. Riffel, C. Kolberg, and W. Partata, Effects of N-acetylcysteine on spinal cord oxidative stress biomarkers in rats with neuropathic pain, Brazilian Journal of Medical and Biological Research., 50 (2017)
• A. Gorlova, D. Pavlov, E. Zubkov, Y. Zorkina, A. Inozemtsev, A. Morozova, and V. Chekhonin, Alteration of oxidative stress markers and behavior of rats in a novel model of depression, Acta Neurobiol. Exp., 79 (2019) 232-238.
• R. Rebai, L. Jasmin and A. Boudah, Agomelatine effects on fat-enriched diet induced neuroinflammation and depression-like behavior in rats, Biomedicine & Pharmacotherapy., 135 (2021) 111246.
• O. Yakovleva, K. Bogatova, R. Mukhtarova, A. Yakovlev, V. Shakhmatova, E. Gerasimova, G. Ziyatdinova, A. Hermann, and G. Sitdikova, Hydrogen sulfide alleviates anxiety, motor, and cognitive dysfunctions in rats with maternal hyperhomocysteinemia via mitigation of oxidative stress, Biomolecules., 10 (2020) 995.
• F. Beheshti, M. Hashemzehi, M. Hosseini, N. Marefati, and S. Memarpour, Inducible nitric oxide synthase plays a role in depression-and anxiety-like behaviors chronically induced by lipopolysaccharide in rats: Evidence from inflammation and oxidative stress, Behavioural brain research., 392 (2020) 112720.
• N. W. Dimer, B. K. Ferreira, J. F. Agostini, M. L. Gomes, L. W. Kist, F. Malgarin, M. Carvalho-Silva, L. M. Gomes, J. Rebelo, and M. J. S. Frederico, Brain bioenergetics in rats with acute hyperphenylalaninemia, Neurochemistry international., 117 (2018) 188-203.
• G. A. Dienel and N. F. Cruz, Biochemical, metabolic, and behavioral characteristics of immature chronic hyperphenylalanemic rats, Neurochemical research., 41 (2016) 16-32.
• K. R. Simon, R. M. dos Santos, G. Scaini, D. D. Leffa, A. P. Damiani, C. B. Furlanetto, J. L. Machado, J. H. Cararo, T. P. Macan, and E. L. Streck, DNA damage induced by phenylalanine and its analogue p-chlorophenylalanine in blood and brain of rats subjected to a model of hyperphenylalaninemia, Biochemistry and Cell Biology., 91 (2013) 319-324.
• L. R. Feksa, A. R. Cornelio, V. C. Rech, C. S. Dutra-Filho, A. T. S. Wyse, M. Wajner, and C. M. D. Wannmacher, Alanine prevents the reduction of pyruvate kinase activity in brain cortex of rats subjected to chemically induced hyperphenylalaninemia, Neurochemical research., 27 (2002) 947-952.
• M. E. K. Hagen, C. D. Pederzolli, A. M. Sgaravatti, R. Bridi, M. Wajner, C. M. Wannmacher, A. T. Wyse, and C. S. Dutra-Filho, Experimental hyperphenylalaninemia provokes oxidative stress in rat brain, Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 1586 (2002) 344-352.
• G. Ellman and H. Lysko, A precise method for the determination of whole blood and plasma sulfhydryl groups, Analytical biochemistry., 93 (1979) 98-102.
• C. Sierra, M. A. Vilaseca, D. Moyano, N. Brandi, J. Campistol, N. Lambruschini, F. J. Cambra, R. Deulofeu, and A. Mira, Antioxidant status in hyperphenylalaninemia, Clinica chimica acta., 276 (1998) 1-9.
• R. Artuch, C. Colomé, M. Vilaseca, C. Sierra, F. Cambra, N. Lambruschini, and J. Campistol, Plasma phenylalanine is asociated with decreased serum ubiquine‐10 concentrations in phenylketonuria, Journal of inherited metabolic disease., 24 (2001) 359-366.
• V. T. Bortoluzzi, C. S. Dutra Filho and C. M. D. Wannmacher, Oxidative stress in phenylketonuria—evidence from human studies and animal models, and possible implications for redox signaling, Metabolic Brain Disease., (2021) 1-21.
• S. Kaufman, An evaluation of the possible neurotoxicity of metabolites of phenylalanine, The Journal of pediatrics., 114 (1989) 895-900.
• N. Ercal, N. Aykin-Burns, H. Gurer-Orhan and J. D. McDonald, Oxidative stress in a phenylketonuria animal model, Free Radic Biol Med., 32 (2002) 906-11.
• K. H. Schulpis, S. Tsakiris, J. Traeger-Synodinos and I. Papassotiriou, Low total antioxidant status is implicated with high 8-hydroxy-2-deoxyguanosine serum concentrations in phenylketonuria, Clinical biochemistry., 38 (2005) 239-242.
• M. Deon, S. S. Landgraf, J. F. Lamberty, D. J. Moura, J. Saffi, M. Wajner, and C. R. Vargas, Protective effect of L-carnitine on Phenylalanine-induced DNA damage, Metabolic Brain Disease. , 30 (2015) 925-933.
• A. Sitta, V. Manfredini, L. Biasi, R. Treméa, I. V. Schwartz, M. Wajner, and C. R. Vargas, Evidence that DNA damage is associated to phenylalanine blood levels in leukocytes from phenylketonuric patients, Mutation Research/Genetic Toxicology and Environmental Mutagenesis., 679 (2009) 13-16.
• C. Colomé, R. Artuch, M.-A. Vilaseca, C. Sierra, N. Brandi, N. Lambruschini, F. J. Cambra, and J. Campistol, Lipophilic antioxidants in patients with phenylketonuria, The American Journal of Clinical Nutrition., 77 (2003) 185-188.
• L. R. Sirtori, C. S. Dutra-Filho, D. Fitarelli, A. Sitta, A. Haeser, A. G. Barschak, M. Wajner, D. M. Coelho, S. Llesuy, A. Belló-Klein, R. Giugliani, M. Deon, and C. R. Vargas, Oxidative stress in patients with phenylketonuria, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease., 1740 (2005) 68-73.
• A. Sitta, A. G. Barschak, M. Deon, J. F. de Mari, A. T. Barden, C. S. Vanzin, G. B. Biancini, I. V. Schwartz, M. Wajner, and C. R. Vargas, L-carnitine blood levels and oxidative stress in treated phenylketonuric patients, Cellular and molecular neurobiology., 29 (2009) 211-218.
• A. Sitta, A. G. Barschak, M. Deon, A. T. Barden, G. B. Biancini, P. R. Vargas, C. F. de Souza, C. Netto, M. Wajner, and C. R. Vargas, Effect of short-and long-term exposition to high phenylalanine blood levels on oxidative damage in phenylketonuric patients, International Journal of Developmental Neuroscience., 27 (2009) 243-247.
• C. G. Fernandes, G. Leipnitz, B. Seminotti, A. U. Amaral, Â. Zanatta, C. R. Vargas, C. S. Dutra Filho, and M. Wajner, Experimental evidence that phenylalanine provokes oxidative stress in hippocampus and cerebral cortex of developing rats, Cellular and molecular neurobiology., 30 (2010) 317-326.
• X. Qiu, Q. Mao, Y. Tang, L. Wang, R. Chawla, H. A. Pliner, and C. Trapnell, Reversed graph embedding resolves complex single-cell trajectories, Nature methods., 14 (2017) 979-982.
• M. S. Cansever, T. Zubarioglu, C. Oruc, E. Kiykim, A. Gezdirici, S. Neselioglu, O. Erel, C. Yalcinkaya, and C. Aktuglu-Zeybek, Oxidative stress among L-2-hydroxyglutaric aciduria disease patients: evaluation of dynamic thiol/disulfide homeostasis, Metabolic brain disease., 34 (2019) 283-288.
• T. Zubarioglu, E. Kiykim, M. S. Cansever, S. Neselioglu, C. Aktuglu-Zeybek, and O. Erel, Evaluation of dynamic thiol/disulphide homeostasis as a novel indicator of oxidative stress in maple syrup urine disease patients under treatment, Metabolic brain disease., 32 (2017) 179-184.
• V. Cam, A. Olgac, M. Kilic, O. Erel, S. Neselioglu, and C. S. Kasapkara, Oxidative Stress in Intoxication Type Inborn Errors of Metabolism using Thiol-Disulfide Ratio, J Coll Physicians Surg Pak., 31 (2021) 663-7.
• P. J. Mc Guire, A. Parikh and G. A. Diaz, Profiling of oxidative stress in patients with inborn errors of metabolism, Molecular genetics and metabolism., 98 (2009) 173-180.