Redox Imbalance in Nasal Epithelial Cells of Primary Ciliary Dyskinesia Patients

Ana Reula; Silvia Castillo-Corullón; Miguel Armengot; Guadalupe Herrera; Amparo Escribano; Francisco Dasí

doi:10.3390/antiox13020190

Redox Imbalance in Nasal Epithelial Cells of Primary Ciliary Dyskinesia Patients

Antioxidants (Basel). 2024 Feb 2;13(2):190. doi: 10.3390/antiox13020190.

Authors

Ana Reula^{1

2

3

4}, Silvia Castillo-Corullón^{1

5}, Miguel Armengot^{4

6}, Guadalupe Herrera⁷, Amparo Escribano^{1

5}, Francisco Dasí^{1

2}

Affiliations

¹ Valencia University Clinical Hospital Research Foundation, Instituto de Investigación Sanitaria INCLIVA, Avda. Menéndez y Pelayo, 4, 46010 Valencia, Spain.
² Rare Respiratory Diseases Research Group, Department of Physiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez, 17, 46010 Valencia, Spain.
³ Biomedical Sciences Department, CEU-Cardenal Herrera University, 12006 Castellón, Spain.
⁴ Molecular, Cellular, and Genomic Biomedicine Group, IIS La Fe, 46026 Valencia, Spain.
⁵ Paediatrics Unit, Department of Pediatrics, Obstetrics and Gynecology, Hospital Clínico Universitario Valencia, University of Valencia, 46022 Valencia, Spain.
⁶ ENT Unit, Department of Surgery, School of Medicine, Hospital La Fe, University of Valencia, Avda. Blasco Ibáñez, 17, 46010 Valencia, Spain.
⁷ Flow Cytometry Unit, Fundación Investigación Hospital Clínico Valencia, Instituto de Investigación Sanitaria INCLIVA, University of Valencia, Avda. Menéndez y Pelayo, 4, 46010 Valencia, Spain.

Abstract

Background: Primary Ciliary Dyskinesia (PCD) represents a rare condition marked by an abnormal mobility pattern of cilia and flagella, resulting in impaired mucociliary clearance. This deficiency leads to recurrent infections and persistent inflammation of the airways. While previous studies have indicated heightened oxidative stress levels in the exhaled breath condensate of pediatric PCD patients, the assessment of oxidative stress within the affected respiratory tissue remains unexplored. Aims: To assess the oxidative status of human nasal epithelial cells (NECs) in PCD patients. Methods: Thirty-five PCD patients and thirty-five healthy control subjects were prospectively included in the study. Levels of reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione (GSH), intracellular Ca²⁺, plasma membrane potential, and oxidative damage in lipids and proteins were measured. In addition, apoptosis and mitochondrial function were analyzed by flow cytometry in NECs. Results: NECs from PCD patients showed reduced levels of apoptosis (p = 0.004), superoxide anion (O₂^-, p = 0.018), peroxynitrite (ONOO^-, p = 0.007), nitric oxide (NO, p = 0.007), mitochondrial hydrogen peroxide (mtH₂O₂, p < 0.0001), and mitochondrial superoxide anion (mtO₂^-, p = 0.0004) and increased mitochondrial mass (p = 0.009) compared to those from healthy individuals. No significant differences were observed in oxidized proteins (p = 0.137) and the oxidized/reduced lipid ratio (p = 0.7973). The oxidative profile of NEC cells in PCD patients, according to their ciliary motility, recurrent otitis, recurrent pneumonia, atelectasis, bronchiectasis, and situs inversus, showed no statistically significant differences in the parameters studied. Conversely, patients with chronic rhinosinusitis exhibited lower levels of ONOO^- than PCD patients without this condition, with no significant differences related to other symptoms. Conclusions: Our findings strongly suggest the presence of a redox imbalance, specifically leaning toward a reductive state, in PCD patients.

Keywords: hydrogen peroxide; nitric oxide; oxidative stress; primary ciliary dyskinesia; rare respiratory diseases.

Abstract

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