Alkyl organophosphate flame retardants (OPFRs) induce lung inflammation and aggravate OVA-simulated asthmatic response via the NF-кB signaling pathway. (May 2022)

• Record Type: Journal Article
• Authors: Meng, Yuan; Xu, Xiaojuan; Xie, Guangming; Zhang, Yunwei; Chen, Shiyan; Qiu, Yanling; Zhu, Zhiliang; Zhang, Hua; Yin, Daqiang
• Is Part Of: Environment international. Volume 163(2022)
• Publication Date: 2022-05
• Subjects: Alkyl OPFRs -- Pulmonary toxicity -- Oxidative stress -- Inflammation -- Asthma; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2022.107209
• Languages: English
• ISSNs: 0160-4120

Abstract

Graphical abstract: Highlights: TnBP and TBOEP caused pulmonary damages by inflammation and oxidative stress. Fkbp5 / Nos3 /MAPK/NF-κB signal pathway was upregulated when exposing to TnBP and TBOEP. TnBP aggravated OVA induced asthmatic inflammatory response with overexpression of IgE. TnBP facilitated OVA-induced asthma by upregulating PI3K/Akt/NF-кB signaling pathway. Abstract: Alkyl organophosphate flame retardants (OPFRs), tri-n-butyl phosphate (TnBP) and tris(2-butoxyethyl) phosphate (TBOEP), are ubiquitously detected in indoor and outdoor environments and their inhalation may result in lung damage. This study examined pulmonary toxicity after exposure to TnBP or TBOEP and investigated aggravation of inflammation and immunoreaction by TnBP in an ovalbumin (OVA)-induced mice model. Transcriptomics were used to further reveal the underlying mechanism. Exposure to TnBP or TBOEP resulted in pathological damage, including edema and thickened alveolar septum. In comparison with the control, enhanced levels of superoxide dismutase (SOD) ( p < 0.01 in TnBP (High) group and p < 0.05 in TBOEP (High) group), glutathione peroxidase (GSH-px) ( p < 0.05), malondialdehyde (MDA) ( p < 0.01), and cytokines under a dose-dependent relationship were noted, and the expression of the Fkbp5 / Nos3 /MAPK/NF-кB signaling pathway ( p < 0.01) was upregulated in the TnBP and TBOEP groups. Moreover, the combined exposure of TnBP and OVA exacerbated the allergic inflammatory response, including airway hyperresponsiveness, leukocytosis, cellular exudation and infiltration, secretion of inflammatory mediators, and higher expression of IgE ( p < 0.01). Transcriptomics results demonstrated that the PI3K/Akt/NF-кB signal pathway was involved in TnBP-aggravated asthmatic mice. Exposure to TnBP or TBOEP resulted in oxidative damage and leukocyte-induced lung injury. TnBP can further facilitate OVA-induced asthma through an inflammatory response. This study is the first to reveal the pulmonary toxicity and potential mechanism induced by OPFRs through an in-vivo model.