Cargando…

Spleen Toxicity of Organophosphorus Flame Retardant TDCPP in Mice and the Related Mechanisms

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is an organophosphorus flame retardant that has been utilized in recent years as a primary replacement for polybrominated diphenyl ethers (PBDEs) in a wide variety of fire-sensitive applications. However, the impact of TDCPP on the immune system has not...

Descripción completa

Detalles Bibliográficos
Autores principales: Cao, Lanqin, Wei, Lai, Du, Qiaoyun, Su, Ying, Ye, Shuzi, Liu, Kaihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051780/
https://www.ncbi.nlm.nih.gov/pubmed/36976996
http://dx.doi.org/10.3390/toxics11030231
_version_ 1785014972084912128
author Cao, Lanqin
Wei, Lai
Du, Qiaoyun
Su, Ying
Ye, Shuzi
Liu, Kaihua
author_facet Cao, Lanqin
Wei, Lai
Du, Qiaoyun
Su, Ying
Ye, Shuzi
Liu, Kaihua
author_sort Cao, Lanqin
collection PubMed
description Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is an organophosphorus flame retardant that has been utilized in recent years as a primary replacement for polybrominated diphenyl ethers (PBDEs) in a wide variety of fire-sensitive applications. However, the impact of TDCPP on the immune system has not been fully determined. As the largest secondary immune organ in the body, the spleen is considered to be an important study endpoint for determining immune defects in the body. The aim of this study is to investigate the effect of TDCPP toxicity on the spleen and its possible molecular mechanisms. In this study, for 28 consecutive days, TDCPP was administered intragastrically (i.g), and we assessed the general condition of mice by evaluating their 24 h water and food intake. Pathological changes in spleen tissues were also evaluated at the end of the 28-day exposure. To measure the TDCPP-induced inflammatory response in the spleen and its consequences, the expression of the critical players in the NF-κB pathway and mitochondrial apoptosis were detected. Lastly, RNA-seq was performed to identify the crucial signaling pathways of TDCPP-induced splenic injury. The results showed that TDCPP intragastric exposure triggered an inflammatory response in the spleen, likely through activating the NF-κB/IFN-γ/TNF-α/IL-1β pathway. TDCPP also led to mitochondrial-related apoptosis in the spleen. Further RNA-seq analysis suggested that the TDCPP-mediated immunosuppressive effect is associated with the inhibition of chemokines and the expression of their receptor genes in the cytokine–cytokine receptor interaction pathway, including four genes of the CC subfamily, four genes of the CXC subfamily, and one gene of the C subfamily. Taken together, the present study identifies the sub-chronic splenic toxicity of TDCPP and provides insights on the potential mechanisms of TDCPP-induced splenic injury and immune suppression.
format Online
Article
Text
id pubmed-10051780
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-100517802023-03-30 Spleen Toxicity of Organophosphorus Flame Retardant TDCPP in Mice and the Related Mechanisms Cao, Lanqin Wei, Lai Du, Qiaoyun Su, Ying Ye, Shuzi Liu, Kaihua Toxics Article Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is an organophosphorus flame retardant that has been utilized in recent years as a primary replacement for polybrominated diphenyl ethers (PBDEs) in a wide variety of fire-sensitive applications. However, the impact of TDCPP on the immune system has not been fully determined. As the largest secondary immune organ in the body, the spleen is considered to be an important study endpoint for determining immune defects in the body. The aim of this study is to investigate the effect of TDCPP toxicity on the spleen and its possible molecular mechanisms. In this study, for 28 consecutive days, TDCPP was administered intragastrically (i.g), and we assessed the general condition of mice by evaluating their 24 h water and food intake. Pathological changes in spleen tissues were also evaluated at the end of the 28-day exposure. To measure the TDCPP-induced inflammatory response in the spleen and its consequences, the expression of the critical players in the NF-κB pathway and mitochondrial apoptosis were detected. Lastly, RNA-seq was performed to identify the crucial signaling pathways of TDCPP-induced splenic injury. The results showed that TDCPP intragastric exposure triggered an inflammatory response in the spleen, likely through activating the NF-κB/IFN-γ/TNF-α/IL-1β pathway. TDCPP also led to mitochondrial-related apoptosis in the spleen. Further RNA-seq analysis suggested that the TDCPP-mediated immunosuppressive effect is associated with the inhibition of chemokines and the expression of their receptor genes in the cytokine–cytokine receptor interaction pathway, including four genes of the CC subfamily, four genes of the CXC subfamily, and one gene of the C subfamily. Taken together, the present study identifies the sub-chronic splenic toxicity of TDCPP and provides insights on the potential mechanisms of TDCPP-induced splenic injury and immune suppression. MDPI 2023-02-27 /pmc/articles/PMC10051780/ /pubmed/36976996 http://dx.doi.org/10.3390/toxics11030231 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cao, Lanqin
Wei, Lai
Du, Qiaoyun
Su, Ying
Ye, Shuzi
Liu, Kaihua
Spleen Toxicity of Organophosphorus Flame Retardant TDCPP in Mice and the Related Mechanisms
title Spleen Toxicity of Organophosphorus Flame Retardant TDCPP in Mice and the Related Mechanisms
title_full Spleen Toxicity of Organophosphorus Flame Retardant TDCPP in Mice and the Related Mechanisms
title_fullStr Spleen Toxicity of Organophosphorus Flame Retardant TDCPP in Mice and the Related Mechanisms
title_full_unstemmed Spleen Toxicity of Organophosphorus Flame Retardant TDCPP in Mice and the Related Mechanisms
title_short Spleen Toxicity of Organophosphorus Flame Retardant TDCPP in Mice and the Related Mechanisms
title_sort spleen toxicity of organophosphorus flame retardant tdcpp in mice and the related mechanisms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051780/
https://www.ncbi.nlm.nih.gov/pubmed/36976996
http://dx.doi.org/10.3390/toxics11030231
work_keys_str_mv AT caolanqin spleentoxicityoforganophosphorusflameretardanttdcppinmiceandtherelatedmechanisms
AT weilai spleentoxicityoforganophosphorusflameretardanttdcppinmiceandtherelatedmechanisms
AT duqiaoyun spleentoxicityoforganophosphorusflameretardanttdcppinmiceandtherelatedmechanisms
AT suying spleentoxicityoforganophosphorusflameretardanttdcppinmiceandtherelatedmechanisms
AT yeshuzi spleentoxicityoforganophosphorusflameretardanttdcppinmiceandtherelatedmechanisms
AT liukaihua spleentoxicityoforganophosphorusflameretardanttdcppinmiceandtherelatedmechanisms