Investigation of Oxidative Stress and Antioxidant Pathways in Nasal Polyp Tissue: Peroxynitrite and Malondialdehyde Compared to NF-E2-related factor 2, Kelch-like ECH-associated protein one and Glycogen Synthase Kinase-3ß An Investigation of NRF2/KEAP1 Pathway in Nasal Polyp Tissue
Article Sidebar
Main Article Content
Abstract
Objective: Nasal polyps are benign mucosal lesions with multifactorial causes that grow into the nasal cavity and are associated with inflammation. This study aims to investigate whether Nrf2, Keap1, GSK-3ß, Peroxynitrite, and malondialdehyde may be used as biochemical markers to determine the relationship between oxidative stress and nasal polyps. The goal is to explore the etiology of nasal polyps and contribute to the literature for a better understanding of the inflammatory pathophysiology of nasal polyps, ultimately leading to the development of new therapeutic approaches.
Materials and Methods: A total of 94 patients aged between 12 and 65 years who underwent a surgical operation for polyps (n = 49, case group) and septoplasty (n=45, controls) between February and September 2022 at the Department of Otorhinolaryngology, Faculty of Medicine, Gaziantep University were included in the study. Tissues taken from the polyp and the inferior turbinate in the case and control groups, respectively, were homogenized at the biochemistry laboratory and investigated using the ELISA method to compare the Nrf-2, Keap1, GSK-3ß, malondialdehyde, and peroxynitrite levels.
Results: Consistent with the study hypothesis, Nrf2 levels were lower, and Keap1 levels were higher in the case group, although the difference was not statistically significant. Although studies have reported increased levels of GSK-3β in chronic rhinosinusitis, they were statistically lower in polyps. This may be associated with the complexity of the GSK-3β network or the adequacy of Keap1 alone for Nrf2 inhibition. Peroxynitrite and malondialdehyde (MDA) levels are indicators of oxidative stress.
Conclusion: Nrf2, Keap1, GSK-3ß, MDA, and Peroxynitritetrite may be involved in the aetiology of nasal polyps based on the study's results. Keap1 and GSK-3ß, Nrf2 and Nrf2 module, actors which regulate oxidative stress, played a role in the pathophysiology of nasal polyps in combination with Peroxynitritetrite and malondialdehyde, according to the study findings. Potential treatments for nasal polyps are better understood through more extensive and well-matched studies.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Accepted 2024-02-01
Published 2024-02-05
References
Hulse K, Stevens W, Tan B, Schleimer R. Pathogenesis of nasal polyposis. Clinical & Experimental Allergy. 2015;45(2):328-46. DOI: https://doi.org/10.1111/cea.12472
Liu T, Zhao F, Xie C, Liu A-M, Li T-L, Chen X, et al. Role of thymic stromal lymphopoietin in the pathogenesis of nasal polyposis. The American journal of the medical sciences. 2011;341(1):40-7. DOI: https://doi.org/10.1097/MAJ.0b013e3181f20489
Bellezza I, Giambanco I, Minelli A, Donato R. Nrf2-Keap1 signaling in oxidative and reductive stress. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2018;1865(5):721-33. DOI: https://doi.org/10.1016/j.bbamcr.2018.02.010
Itoh K, Ishii T, Wakabayashi N, Yamamoto M. Regulatory mechanisms of cellular response to oxidative stress. Free Radical Research. 1999;31(4):319-24. DOI: https://doi.org/10.1080/10715769900300881
Rada P, Rojo AI, Evrard-Todeschi N, Innamorato NG, Cotte A, Jaworski T, et al. Structural and functional characterization of Nrf2 degradation by the glycogen synthase kinase 3/β-TrCP axis. Molecular and cellular biology. 2012;32(17):3486-99. DOI: https://doi.org/10.1128/MCB.00180-12
Kobayashi M, Yamamoto M. Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation. Antioxidants & redox signaling. 2005;7(3-4):385-94. DOI: https://doi.org/10.1089/ars.2005.7.385
Kaspar JW, Niture SK, Jaiswal AK. Nrf2: INrf2 (Keap1) signaling in oxidative stress. Free Radical Biology and Medicine. 2009;47(9):1304-9. DOI: https://doi.org/10.1016/j.freeradbiomed.2009.07.035
Shilpasree A, Kumar K, Itagappa M, Ramesh G. Study of oxidative stress and antioxidant status in oral cancer patients. International Journal of Oral and Maxillofacial Pathology. 2013;4(2):2-6.
Sezer K, Keskin M. Role of the free oxygen radicals on the pathogenesis of the diseases. Sağlık Bilimleri Veteriner Dergisi, Fırat Üniversitesi. 2014;28(1):49-56.
Pawliczak R, Lewandowska-Polak A, Kowalski ML. Pathogenesis of nasal polyps: an update. Current allergy and asthma reports. 2005;5(6):463-71. DOI: https://doi.org/10.1007/s11882-005-0027-7
Johansson L, Åkerlund A, Melén I, Holmberg K, Bende M. Prevalence of nasal polyps in adults: the Skovde population-based study. Annals of Otology, Rhinology & Laryngology. 2003;112(7):625-9. DOI: https://doi.org/10.1177/000348940311200709
Larsen K, Tos M. The estimated incidence of symptomatic nasal polyps. Acta oto-laryngologica. 2002;122(2):179-82. DOI: https://doi.org/10.1080/00016480252814199
Popa-Wagner A, Mitran S, Sivanesan S, Chang E, Buga A-M. ROS and brain diseases: the good, the bad, and the ugly. Oxidative medicine and cellular longevity. 2013;2013. DOI: https://doi.org/10.1155/2013/963520
Topal O, Kulaksızoglu S, Erbek SS. Oxidative stress and nasal polyposis: does it affect the severity of the disease? American Journal of Rhinology & Allergy. 2014;28(1):e1-e4. DOI: https://doi.org/10.2500/ajra.2014.28.3963
Akyigit A, Keles E, Etem EO, Ozercan I, Akyol H, Sakallioglu O, et al. Genetic polymorphism of antioxidant enzymes in eosinophilic and non-eosinophilic nasal polyposis. European Archives of Oto-Rhino-Laryngology. 2017;274(1):267-73. DOI: https://doi.org/10.1007/s00405-016-4259-z
Cekin E, Ipcioglu O, Erkul B, Kapucu B, Ozcan O, Cincik H, et al. The association of oxidative stress and nasal polyposis. Journal of International Medical Research. 2009;37(2):325-30. DOI: https://doi.org/10.1177/147323000903700206
Dagli M, Eryilmaz A, Besler T, Akmansu H, Acar A, Korkmaz H. Role of free radicals and antioxidants in nasal polyps. The Laryngoscope. 2004;114(7):1200-3. DOI: https://doi.org/10.1097/00005537-200407000-00013
Mateo AO, de Artiñano MAA. Nitric oxide reactivity and mechanisms involved in its biological effects. Pharmacological research. 2000;42(5):421-7. DOI: https://doi.org/10.1006/phrs.2000.0701
Kang B-H, Huang N-C, Wang H-W. Possible involvement of nitric oxidePeroxynitritetrite in nasal polyposis. American journal of rhinology. 2004;18(4):191-6. DOI: https://doi.org/10.1177/194589240401800401
Giannessi F, Ursino F, Fattori B, Giambelluca MA, Scavuzzo MC, Nacci A, et al. Expression of 3-nitrotyrosine, a markerPeroxynitritetrite, in nasal polyps of nonatopic patients. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research. 2010;16(4):CR172-9.
Chen W, Liu Z, Ye J. Relationship among the expression of GSK3β, PI3K/Akt, and IL-6 in chronic rhinosinusitis. Zhonghua er bi yan hou tou Jing wai ke za zhi= Chinese Journal of Otorhinolaryngology Head and Neck Surgery. 2013;48(2):128-34.
Tian T, Yuan Q, Ye J. Relationship and significance among IL-6, PI3K/Akt and GSK 3β in chronic rhinosinusitis. Lin Chuang er bi yan hou tou Jing wai ke za zhi= Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery. 2016;30(23):1859-64.
Cuadrado A. Structural and functional characterization of Nrf2 degradation by glycogen synthase kinase 3/β-TrCP. Free Radical Biology and Medicine. 2015;88:147-57. DOI: https://doi.org/10.1016/j.freeradbiomed.2015.04.029
Shaw P, Chattopadhyay A. Nrf2–ARE signalling in cellular protection: Mechanism of action and the regulatory mechanisms. Journal of Cellular Physiology. 2020;235(4):3119-30. DOI: https://doi.org/10.1002/jcp.29219
Kim SG, Kim SO. PKC downstream of PI3-kinase regulates peroxynitrite formation for Nrf2-mediated GSTA2 induction. Archives of pharmacal research. 2004;27(7):757-62. DOI: https://doi.org/10.1007/BF02980145
Shacka J, Garner M, Gonzalez J, Ye Y, D'alessandro T, Estevez A. Two distinct signalling pathways regulate peroxynitrite-induced apoptosis in PC12 cells. Cell Death & Differentiation. 2006;13(9):1506-14. DOI: https://doi.org/10.1038/sj.cdd.4401831