Redox Imbalance in Cystic Fibrosis: The Multifaceted Role of Oxidative Stress

Cystic fibrosis (CF), a severe genetic disorder stemming from mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, is characterized by a complex interplay of chronic inflammation and heightened oxidative stress, resulting in substantial patient morbidity. The diverse array of CFTR mutations, categorized into seven distinct classes based on their functional impact on the CFTR protein, presents a significant obstacle to effective therapeutic intervention. While CFTR modulator therapies offer clinical benefits, their applicability is restricted to specific mutation classes, leaving a considerable portion of the CF patient population with unmet therapeutic needs. This review provides a critical analysis of the intricate role of oxidative stress in CF, meticulously examining its origins, mechanistic pathways and downstream pathological consequences, with particular emphasis on lipid peroxidation (LPO). It elucidates the nuanced connection between LPO and inflammatory processes driven by cellular stressors such as endoplasmic reticulum dysfunction, mitochondrial impairment and persistent bacterial infections. Furthermore, it evaluates the current landscape of therapeutic proposals targeting oxidative stress, including antioxidant interventions, and explores the potential of microRNAs (miRNAs) as novel targets. This review aims to synthesize existing research to provide a comprehensive understanding of oxidative stress involvement in CF pathogenesis while critically appraising the advantages and limitations of current antioxidant therapeutic strategies.