PMID- 35358787
OWN - NLM
STAT- MEDLINE
DCOM- 20220426
LR  - 20220616
IS  - 1873-6750 (Electronic)
IS  - 0160-4120 (Linking)
VI  - 163
DP  - 2022 May
TI  - Alkyl organophosphate flame retardants (OPFRs) induce lung inflammation and 
      aggravate OVA-simulated asthmatic response via the NF-small ka, CyrillicB signaling pathway.
PG  - 107209
LID - S0160-4120(22)00135-0 [pii]
LID - 10.1016/j.envint.2022.107209 [doi]
AB  - 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-small ka, CyrillicB 
      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-small ka, CyrillicB 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.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Meng, Yuan
AU  - Meng Y
AD  - Key Laboratory of Yangtze River Water Environment, College of Environmental 
      Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai 
      Institute of Pollution Control and Ecological Security, 1239 Siping Road, 
      Shanghai 200092, China.
FAU - Xu, Xiaojuan
AU  - Xu X
AD  - Department of Pathology and Pathophysiology, Tongji University School of 
      Medicine, Shanghai 200092, China.
FAU - Xie, Guangming
AU  - Xie G
AD  - Tongji University School of Medicine, Shanghai 200092, China.
FAU - Zhang, Yunwei
AU  - Zhang Y
AD  - Tongji University School of Medicine, Shanghai 200092, China.
FAU - Chen, Shiyan
AU  - Chen S
AD  - Key Laboratory of Yangtze River Water Environment, College of Environmental 
      Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai 
      Institute of Pollution Control and Ecological Security, 1239 Siping Road, 
      Shanghai 200092, China.
FAU - Qiu, Yanling
AU  - Qiu Y
AD  - Key Laboratory of Yangtze River Water Environment, College of Environmental 
      Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai 
      Institute of Pollution Control and Ecological Security, 1239 Siping Road, 
      Shanghai 200092, China. Electronic address: ylqiu@tongji.edu.cn.
FAU - Zhu, Zhiliang
AU  - Zhu Z
AD  - Key Laboratory of Yangtze River Water Environment, College of Environmental 
      Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai 
      Institute of Pollution Control and Ecological Security, 1239 Siping Road, 
      Shanghai 200092, China.
FAU - Zhang, Hua
AU  - Zhang H
AD  - Key Laboratory of Yangtze River Water Environment, College of Environmental 
      Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai 
      Institute of Pollution Control and Ecological Security, 1239 Siping Road, 
      Shanghai 200092, China.
FAU - Yin, Daqiang
AU  - Yin D
AD  - Key Laboratory of Yangtze River Water Environment, College of Environmental 
      Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai 
      Institute of Pollution Control and Ecological Security, 1239 Siping Road, 
      Shanghai 200092, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220328
PL  - Netherlands
TA  - Environ Int
JT  - Environment international
JID - 7807270
RN  - 0 (Flame Retardants)
RN  - 0 (NF-kappa B)
RN  - 0 (Organophosphates)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Animals
MH  - *Asthma/chemically induced
MH  - *Flame Retardants/toxicity
MH  - Mice
MH  - NF-kappa B
MH  - Organophosphates/toxicity
MH  - Ovalbumin
MH  - Phosphatidylinositol 3-Kinases
MH  - *Pneumonia
MH  - Signal Transduction
OTO - NOTNLM
OT  - Alkyl OPFRs
OT  - Asthma
OT  - Inflammation
OT  - Oxidative stress
OT  - Pulmonary toxicity
EDAT- 2022/04/01 06:00
MHDA- 2022/04/27 06:00
CRDT- 2022/03/31 20:12
PHST- 2021/10/31 00:00 [received]
PHST- 2022/03/23 00:00 [revised]
PHST- 2022/03/23 00:00 [accepted]
PHST- 2022/04/01 06:00 [pubmed]
PHST- 2022/04/27 06:00 [medline]
PHST- 2022/03/31 20:12 [entrez]
AID - S0160-4120(22)00135-0 [pii]
AID - 10.1016/j.envint.2022.107209 [doi]
PST - ppublish
SO  - Environ Int. 2022 May;163:107209. doi: 10.1016/j.envint.2022.107209. Epub 2022 
      Mar 28.