Niacin Supplementation Alleviates TCIPP-Induced Lung Injury via Inhibition of the NF-κB Signaling Pathway

Tris(1-chloro-2-propyl) phosphate (TCIPP) is an emerging environmental pollutant associated with adverse respiratory effects, yet whether niacin has a protective effect on lung function remains unclear. Data from 1031 participants in the 2011-2012 National Health and Nutrition Examination Survey (NHANES) were analyzed using multiple linear regression to assess associations between urinary bis(1,3-dichloro-2-propyl) phosphate (BCIPP), dietary niacin intake, and pulmonary function. Animal models were established to investigate TCIPP-induced lung injury and the protective effects of niacin. Lung injury was assessed by histopathology, lung function, inflammation, and oxidative stress-related indicators. Comparative Toxicogenomics Database (CTD), molecular docking, and Western blot were performed to explore underlying mechanisms. Higher urinary BCIPP concentration was associated with reduced lung function, whereas higher dietary niacin intake was associated with improved lung function. Notably, BCIPP levels showed positive associations between dietary niacin intake and FEV₁ [β (95% CI) = 0.11 (0.06, 0.16), <i>p_adj</i> < 0.001] and FVC [β (95% CI) = 0.09 (0.05, 0.13), <i>p_adj</i> < 0.001] in males with lower BCIPP exposure. In male mice, TCIPP exposure caused dose-dependent lung injury, inflammation, and oxidative stress, while niacin supplementation alleviated lung damage, improved lung function, and restored antioxidant defenses by inhibiting NF-κB phosphorylation. Niacin supplementation alleviated TCIPP-induced lung injury in males by inhibiting oxidative stress and NF-κB activation, suggesting niacin as a potential nutritional strategy to improve lung function.