College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin, 150030, China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
Environ Pollut. 2020 Dec;267:115564. doi: 10.1016/j.envpol.2020.115564. Epub 2020 Sep 1.
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.
邻苯二甲酸二丁酯（DBP）是环境中一种重要的塑料污染物，已知会导致器官毒性。虽然目前的研究表明 DBP 诱导的器官毒性与氧化应激有关，但 DBP 对肺部的毒性作用尚未完全阐明。因此，我们使用 DBP 诱导的大鼠过敏性气道炎症模型，研究了 DBP 诱导肺毒性的潜在机制。结果表明，慢性暴露于 DBP 可诱导组织病理学损伤、炎症、氧化应激、细胞凋亡，并增加胸腺基质淋巴细胞生成素（TSLP）及其下游蛋白 Janus 激酶 1（JAK1）和信号转导和转录激活因子 6（STAT6）的蛋白水平。此外，DBP 暴露抑制核因子-红细胞 2 相关因子 2（Nrf2）及其靶基因 NAD（P）H 醌氧化还原酶 1（NQO1）和血红素加氧酶 1（HO-1）的水平。此外，通过体外实验，我们发现 DBP 可诱导氧化应激，降低细胞活力，并抑制小鼠肺泡型 II 上皮细胞系中的 Nrf2/HO-1/NQO1 通路。总的来说，这些数据表明 DBP 通过抑制 Nrf2/TSLP/JAK1 通路诱导大鼠过敏性气道炎症。
