An investigation of Nrf-2/Keap1 pathway in nasal polyp tissue

Purpose: Nasal Polyps are benign mucosal lesions with multifactorial causes of unknown origin that grow into the nasal cavity accompanied by mucosal inflammation. The present study aimed to investigate whether Nrf2, Keap1, GSK-3ß, Peroxynitrite, and Malondialdehyde could be used as biochemical markers in order to see the relationship between oxidative stress and nasal polyp and the etiology of nasal polyps, and to contribute to the literature for a better understanding of the inflammatory pathophysiology of the polyp and ultimately the development of new pharmacotherapeutic approaches. Materıal And Methods: A total of 94 patients aged between of 12 and 65 years, who received surgical operation for polyps (n=49, case group) and who underwent septoplasty (n=45, controls), between February and September 2022 at 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 group and the control group, respectively, were homogenized at the biochemistry laboratory and investigated with the ELISA method with an aim to compare the Nrf-2, Keap1, GSK-3ß, malondialdehyde, and peroxynitrite levels. Results: Consistent with the study hypothesis, the Nrf2 level was lower and Keap1 was higher in the case group, albeit not statistically significant. Although increased levels of GSK-3β were reported by studies on chronic rhinosinusitis, it was statistically lower in patients polyps, inconsistent with the relevant literature. This might be associated with the complexity of the GSK-3β network or the adequacy of Keap1 alone for Nrf2 inhibition. Peroxynitrite and malondialdehyde levels, as indicators of oxidative stress, were high, consistent with the relevant literature. Conclusıon: The study data indicated certain evidence that Nrf2, Keap1, GSK-3ß, MDA, and peroxynitrite might have played a role in the etiology of nasal polyps. In conclusion, the study results suggested that Keap1 and GSK-3ß, the Nrf2 and Nrf2 modulators, which have a central role in the regulation of oxidative stress, played a role in the pathophysiology of nasal polyps in combination with peroxynitrite and malondialdehyde. Further studies with a larger and well-matched population would provide a better understanding of the pathophysiology of nasal polyps, providing guidance for potential treatments. Keywords: Gsk-3ß, Keap 1, Malondialdehyde, Nasal Polyp, NRF2 Peroxynitrite, Oxidative Stress,