Lipid Peroxidation Structure Selectivity: A Clue to Coal Workers' Pneumoconiosis

Coal workers' pneumoconiosis (CWP), resulting from the inhalation of coal dust mixtures, is one of the leading occupational diseases globally. Despite its seriousness, there is still no effective curative method available for CWP. Therefore, a systemic understanding of CWP's pathogenesis is urgently needed. Peroxidation is an oxidation chain reaction in which lipids (glycerophospholipids and other membrane lipids) are degraded into excretory forms, such as fatty aldehydes. This process involves a series of enzymes that catalyze the reactions leading to lipid degradation. Our previous work identified specific regulatory mechanisms in lipid peroxidation processes triggered by diseases or various interventions. To gain a comprehensive understanding of lipid peroxidation, we developed a systematic profiling strategy that allows for the detailed observation of these oxidative processes. Additionally, we adapted this profiling strategy to investigate risk factors associated with coal workers' pneumoconiosis (CWP). By applying our methods to the study of CWP, we aimed to uncover the metabolic and molecular changes induced by coal dust inhalation, providing insights that could contribute to better prevention and treatment strategies for this occupational disease. To comprehensively investigate the lung alterations associated with CWP, both a cohort of coal miners and a CWP rat model were studied. Through the analysis of lipid peroxidation alterations associated with CWP occurrence, several CYP subtype-specific metabolic processes were identified. These findings suggest that coal-derived polycyclic aromatic hydrocarbons (PAHs) are major risk factors for CWP due to the specific activation of the Aryl Hydrocarbon Receptor (AhR) pathway. Further evidence at the gene level and morphological changes supports the role of coal-derived PAHs as key factors in the development of CWP. Hence, it is crucial to consider the toxicity induced by PAHs in the prevention and treatment of CWP.