SavedAdd your journal

Journals / Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi / 2026 / Volume: 11 Issue: 1

Rat PKU Model Display Gender-Based Neuroinflammatory Changes: Proinflamatuary Cytokines and Lipid Peroxidation

Sıçan PKU Modeli Cinsiyete Dayalı Nöroinflamatuar Değişiklikler Gösterir: Proinflamatuar Sitokinler ve Lipid Peroksidasyonu

Çiğdem Çiçek(YÜKSEK İHTİSAS ÜNİVERSİTESİ)0000-0001-5481-4438
Müslüm Gök(MUGLA SITKI KOCMAN UNIVERSITY)0000-0003-2875-291X
Ebru Bodur(HACETTEPE UNIVERSITY)0000-0001-5829-5487
Pages
—
Publication Date
2024-04-30
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Our results showed that in phenylketonuria there was an increase in lipid peroxidation compared to controls, which was significantly different only in males (p<0.001).

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Phenylketonuria (PKU) results from congenital defects of amino acid metabolism.
📊
Key Findings & Data:Chemically-induced rat phenylketonuria model of both genders was generated to examine the role of inflammatory response, lipid peroxidation and oxidative stress in the prefrontal cortex.
💡
Conclusion & Impact:Our results showed that in phenylketonuria there was an increase in lipid peroxidation compared to controls, which was significantly different only in males (p<0.001).
🔬Design:Modeling & Simulation
📍Scope:Comprehensive Sample
⚙️Variables:Gender Based · Phenylketonuria · Neuro-inflammation

Abstract

Phenylketonuria (PKU) results from congenital defects of amino acid metabolism. Accumulated phenylalanine crosses the blood-brain barrier and causes permanent brain damage, but the neuro-pathophysiology underlying phenylketonuria is not fully understood. Chemically-induced rat phenylketonuria model of both genders was generated to examine the role of inflammatory response, lipid peroxidation and oxidative stress in the prefrontal cortex. Our results showed that in phenylketonuria there was an increase in lipid peroxidation compared to controls, which was significantly different only in males (p<0.001). In male rat PKU groups, statistically significant differences were also observed in serum tryptophan (p<0.001) and interleukin-1β levels (p=0.014) as compared to male controls. In this study, gender-based changes in neuroinflammation and lipid peroxidation were reported for the first time in a PKU model.

Özet

Fenilketonüri (PKU), amino asit metabolizmasının konjenital kusurlarından kaynaklanır. Birikmiş fenilalanin kan-beyin bariyerini geçer ve kalıcı beyin hasarına neden olur, ancak fenilketonürinin altında yatan nöro-patofizyoloji tam olarak anlaşılamamıştır. Prefrontal kortekste inflamatuar yanıtın, lipit peroksidasyonunun ve oksidatif stresin rolünü incelemek için her iki cinsiyete ait kimyasal olarak indüklenmiş sıçan Fenilketonüri modeli oluşturuldu. Sonuçlarımız Fenilketonüride kontrollere kıyasla lipit peroksidasyonunda artış olduğunu gösterdi; bu artış sadece erkeklerde anlamlı derecede farklıydı (p<0.001). Erkek sıçan PKU gruplarında serum triptofan (p<0.001) ve interlökin-1β düzeylerinde (p=0.014) erkek kontrollere göre anlamlı farklılıklar gözlendi. Bu çalışma ile cinsiyete ilk kez bir PKU modelinde cinsiyete bağlı nöroinflamasyon ve lipid peroksidasyonunda değişiklikler rapor edilmiştir.

🔖

Cite This Article

Çiçek, Ç., Gök, M., Bodur, E. (2024). Rat PKU Model Display Gender-Based Neuroinflammatory Changes: Proinflamatuary Cytokines and Lipid Peroxidation. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, Volume: 11 Issue: 1. https://doi.org/10.47572/muskutd.1388547

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (40)

  1. Scriber C. Hyperphenylalaninemia: phenylalanine hydroxylase deficiency. The metabolic and molecular bases of inherited disease. 2001:1667-724.
  2. Blau N, Van Spronsen FJ, Levy HL. Phenylketonuria. The Lancet. 2010;376(9750):1417-27.
  3. Blau N. Genetics of phenylketonuria: then and now. Human mutation. 2016;37(6):508-15.
  4. Sierra C, Vilaseca MA, Moyano D, et al. Antioxidant status in hyperphenylalaninemia. Clin Chim Acta. 1998;276:1-9.
  5. Wajner M, Latini A, Wyse A, et al. The role of oxidative damage in the neuropathology of organic acidurias: insights from animal studies. J Inherit Metab Dis. 2004;27(4):427-48.
  6. Sirtori L, Dutra-Filho C, Fitarelli D, et al. Oxidative stress in patients with phenylketonuria. Biochim Biophys Acta. 2005;1740(1):68-73.
  7. Sitta A, Manfredini V, Biasi L, et al. Evidence that DNA damage is associated to phenylalanine blood levels in leukocytes from phenylketonuric patients. Mutat Res. 2009;679(1-2):13-6.
  8. Hagen MEK, Pederzolli CD, Sgaravatti AM, et al. Experimental hyperphenylalaninemia provokes oxidative stress in rat brain. Biochim Biophys Acta. 2002;1586:344-52.
  9. Fernandes CG, Leipnitz G, Seminotti B, et al. Experimental evidence that phenylalanine provokes oxidative stress in hippocampus and cerebral cortex of developing rats. Cell Mol Neurobiol. 2010;30(2):317-26.
  10. Vargas C, Wajner M, Sitta A. Oxidative stress in phenylketonuric patients. Mol Genet Metab. 2011;104:S97-S9.
  11. Allan SM, Rothwell NJ. Inflammation in central nervous system injury. Philos Trans R Soc Lond B Biol Sci. 2003;358(1438):1669-77.
  12. Abbas AK, Murphy KM, Sher A. Functional diversity of helper T lymphocytes. Nature. 1996;383(6603):787-93.
  13. Cai Z, Hussain MD, Yan L-J. Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer's disease. Int J Neurosci. 2014;124(5):307-21.
  14. Qiu X, Mao Q, Tang Y, et al. Reversed graph embedding resolves complex single-cell trajectories. Nat Methods. 2017;14(10):979-82.
  15. Sturza A, Popoiu CM, Ionică M, et al. Monoamine Oxidase-Related Vascular Oxidative Stress in Diseases Associated with Inflammatory Burden. Oxid Med Cell Longev. 2019;2019:8954201.
  16. Delumeau JC, Bentué-Ferrer D, Gandon JM, et al. Monoamine oxidase inhibitors, cognitive functions and neurodegenerative diseases. J Neural Transm Suppl. 1994;41:259-66.
  17. Grailhe R, Cardona A, Even N, et al. Regional changes in the cholinergic system in mice lacking monoamine oxidase A. Brain Res Bull. 2009;78(6):283-9.
  18. Sakurai T, Gamo NJ, Hikida T, et al. Converging models of schizophrenia – Network alterations of prefrontal cortex underlying cognitive impairments. Prog Neurobiol. 2015;134:178-201.
  19. Simon KR, dos Santos RM, Scaini G, et al. DNA damage induced by phenylalanine and its analogue p-chlorophenylalanine in blood and brain of rats subjected to a model of hyperphenylalaninemia. Biochem Cell Biol. 2013;91(5):319-24.
  20. Wang L, Erlandsen H, Haavik J, et al. Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin. Biochemistry. 2002;41(42):12569-74.
  21. Rech VC, Feksa LR, Dutra-Filho CS, et al. Inhibition of the mitochondrial respiratory chain by phenylalanine in rat cerebral cortex. Neurochem Res. 2002;27(5):353-7.
  22. Cicek C, Eren-Koçak E, Telkoparan-Akillilar P, et al. cAMP/PKA-CREB-BDNF signaling pathway in hippocampus of rats subjected to chemically-induced phenylketonuria. Metab Brain Dis. 2022;37(2):545-57.
  23. Lowry O, Rosebrough N, Farr AL, et al. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-75.
  24. Flohé L, Günzler WA. Assays of glutathione peroxidase. Methods Enzymol. 1984;105:114-21.
  25. Staal GJ, Visser J, and Veeger C. The reaction mechanism of glutathione reductase from human erythrocytes. Biochim Biophys Acta. 1969;185:39.
  26. Razali NM, Wah YB. Power comparisons of shapiro-wilk, kolmogorov-smirnov, lilliefors and anderson-darling tests. J stat model analy. 2011;2(1):21-33.
  27. Guerra IMS, Ferreira HB, Neves B, et al. Lipids and phenylketonuria: Current evidences pointed the need for lipidomics studies. Arch Biochem Biophys. 2020;688:108431.
  28. Azabdaftari A, van der Giet M, Schuchardt M, et al. The cardiovascular phenotype of adult patients with phenylketonuria. Orphanet J Rare Dis. 2019;14(1):213.
  29. Deon M, Sitta A, Faverzani JL, et al. Urinary biomarkers of oxidative stress and plasmatic inflammatory profile in phenylketonuric treated patients. Int J Dev Neurosci. 2015;47:259-65.
  30. Sturza A, Popoiu CM, Ionică M, et al. Monoamine oxidase-related vascular oxidative stress in diseases associated with inflammatory burden. Oxid Med Cell Longev. 2019;2019:8954201.
  31. Rațiu C, Uțu D, Petruș A, et al. Monoamine oxidase inhibition improves vascular function and reduces oxidative stress in rats with lipopolysaccharide-induced inflammation. Gen Physiol Biophys. 2018;37(6):687-94.
  32. Naoi M, Maruyama W, Shamoto-Nagai M. Type A and B monoamine oxidases distinctly modulate signal transduction pathway and gene expression to regulate brain function and survival of neurons. J Neural Transm (Vienna). 2018;125(11):1635-50.
  33. Ghozlan A, Varoquaux O, Abadie V. Is monoamine oxydase-B a modifying gene and phenylethylamine a harmful compound in phenylketonuria? Mol Genet Metab. 2004;83(4):337-40.
  34. Boulet L, Besson G, Faure P, et al. [Tryptophan metabolism: utility of plasmatic assay in phenylketonuria, a study in 6 adult patients]. Ann Biol Clin (Paris). 2018;76(2):150-6.
  35. Martinez‐Cruz F, Pozo D, Osuna C, et al. Oxidative stress induced by phenylketonuria in the rat: Prevention by melatonin, vitamin E, and vitamin C. J Neurosci Res. 2002;69(4):550-8.
  36. Bortoluzzi VT, Brust L, Preissler T, et al. Creatine plus pyruvate supplementation prevents oxidative stress and phosphotransfer network disturbances in the brain of rats subjected to chemically-induced phenylketonuria. Metab Brain Dis. 2019;34(6):1649-60.
  37. Mozrzymas R, Duś-Żuchowska M, Kałużny Ł, et al. Phenylketonuria is not a risk factor for changes of inflammation status as assessed by interleukin 6 and interleukin 8 concentrations. Acta Sci Pol Technol Aliment. 2016;15(2):221-5.
  38. Diamond A. The development and neural bases of memory functions as indexed by the AB and delayed response tasks in human infants and infant monkeys. Ann N Y Acad Sci. 1990;608(1):267-317.
  39. Diamond A, Ciaramitaro V, Donner E, et al. An animal model of early-treated PKU. J Neurosci. 1994;14(5):3072.
  40. Diamond A, Prevor MB, Callender G, et al. Prefrontal cortex cognitive deficits in children treated early and continuously for PKU. Monogr Soc Res Child Dev. 1997;62(4):i-v.