4-Hydroxynonenal, a Potential Biomarker for Lung Inflammatory Diseases

Asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS) are the major lung inflammatory complications affecting the global population. Exposure to allergens, infections, smoking, and environmental pollutants could cause persistent oxidative stress and dysregulated immune responses, leading to lung inflammatory complications. Increased oxidative stress can lead to lipid peroxidation and the formation of toxic lipid aldehydes. One of the major lipid aldehydes formed during lipid peroxidation is 4-hydroxy-2-nonenal (4-HNE). 4-HNE is well known to covalently modify proteins, nucleic acids, and lipids, thus modifying cellular signaling pathways and inflammatory cascades. Increased levels of 4-HNE have been identified in lung tissues, bronchoalveolar lavage (BAL) fluid, and the serum of patients with inflammatory lung conditions. Further, 4-HNE contributes to airway remodeling, mitochondrial dysfunction, and modulation of inflammatory responses in the lung epithelial cells. Recent studies also indicate the potential role of 4-HNE as an important mediator and a potential biomarker of various human disease progression, including the diagnosis and monitoring of lung inflammatory diseases. In this narrative review, we discuss current evidence on the pathological role of 4-HNE, its potential as a biomarker, and its importance for early detection and for potential therapeutic strategies in lung inflammatory complications.