Dibutyl phthalate induces allergic airway inflammation in rats via inhibition of the Nrf2/TSLP/JAK1 pathway

Dibutyl phthalate (DBP), an important plastic contaminant in the environment, is known to cause organ toxicity. Although current research has shown that DBP-induced organ toxicity is associated with oxidative stress, the toxic effect of DBP on the lungs have not been fully elucidated. Therefore, we investigated the potential mechanism by which DBP induces pulmonary toxicity using a model of DBP-induced allergic airway inflammation in rats. The results showed that chronic exposure to DBP induced histopathological damage, inflammation, oxidative stress, apoptosis, and increased the protein levels of thymic stromal lymphopoietin (TSLP) and its downstream protein Janus kinase 1 (JAK1) and signal transducer and activator of transcription 6 (STAT6). Moreover, DBP exposure inhibited nuclear factor-erythroid-2-related factor 2 (Nrf2) and levels of its target genes NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1). Additionally, using in vitro experiments, we found that DBP induced oxidative stress, reduced cell viability, and inhibited the Nrf2/HO-1/NQO1 pathway in mouse alveolar type II epithelial cell line. Overall, these data demonstrate that DBP induces allergic airway inflammation in rats via inhibition of the Nrf2/TSLP/JAK1 pathway. [Display omitted] •Dibutyl phthalate (DBP) exposure induces allergic airway inflammation in rats.•DBP inhibits the Nrf2 antioxidant response pathway in the lung.•DBP-induced lung toxicity in rats is reversed by Res which is an activator of Nrf2.•DBP-induced oxidative stress triggers allergic airway inflammation.•DBP induces allergic airway inflammation via inhibiting the Nrf2/TSLP/JAK1 pathway.