Perfluorooctanoic acid induced lung toxicity via TGF-β1/Smad pathway, crosstalk between airway hyperresponsiveness and fibrosis: withdrawal impact

Perfluorooctanoic acid (PFOA) is an environmental persistent agent to which humans are exposed daily through food and water. This study investigated the lung toxic effects induced by ingested PFOA (30 mg/kg/day) for 8 weeks in adult male rats and the impact following 8 weeks of its withdrawal. PFOA increased MDA and reduced TAC inducing oxidative stress. It induced airway hyperresponsiveness (AHR) via increased bronchoalveolar lavage fluid (BALF) IL-4, IL-5, IL-13, IL-9, eosinophil count, TNF-α, and IL-1ß; reduced IL-12; increased serum IgE; and increased urocortin expression in lung tissues. Moreover, it induced pulmonary fibrosis via increased serum KL-6, and SFTP-D, altered pulmonary structure, and increased deposition of collagen fibers in lung tissues. Furthermore, it increased TGF-β1, Smad2, and Smad3 and reduced Smad7 gene expression in lung tissues. These gene alterations were positively correlated with AHR and fibrosis-related factors. The recovered lung upon PFOA withdrawal showed complete resolution of oxidative stress and slight amelioration of other studying parameters. Exposure to PFOA induced lung toxicity by disrupting the TGF-β1/Smad signaling pathway, which acts as a crosstalk between AHR and fibrosis. Additionally, PFOA altered pulmonary architecture, triggered inflammation, and caused oxidative stress. The lung exhibited partial alleviation upon recovery.

Graphical Abstract