TY - JOUR
T1 - Dimethyl phthalate induces blood immunotoxicity through oxidative damage and caspase-dependent apoptosis
AU - Chi, Zhenxing
AU - Lin, Hongwei
AU - Wang, Xiaodan
AU - Meng, Xuanlin
AU - Zhou, Jieqiong
AU - Xiang, Li
AU - Cao, Guodong
AU - Wu, Pengfei
AU - Cai, Zongwei
AU - Zhao, Xingchen
N1 - This work was supported by the National Natural Science Foundation of China (No. 21707026 ), Guangzhou Key Laboratory of Environmental Exposure and Health (No. GZKLEEH201613 ), and the Natural Science Foundation of Shandong Province (No. ZR2014BQ033 ).
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/9/10
Y1 - 2022/9/10
N2 - Dimethyl phthalate (DMP), a low-molecular-weight phthalate ester, exists in ectoparasiticides, plastics, and insect repellants, and has been linked to neurotoxic, reproductive, and endocrine disruptive responses. However, its blood immunotoxic effects and mechanism are still poorly understood. In this study, rats were exposed to gradient concentrations of DMP through intragastric administration to assess the blood immunotoxic effects in the combined assay of biomarker, cytometry, and transcriptomics. DMP treatment altered the redox status of rats, thus causing oxidative damage. Significantly decreased blood cell counts and disordered antibody and cytokine secretion were observed in treated rats, suggesting the suppressed immune defense and destructed inflammatory regulation. Flow cytometry showed that in lymphocytes, especially CD3+CD4+ T cells, the occurrence of apoptosis/necrosis was positively related to DMP exposure level. Transcriptomics revealed an oxidative stress-related mechanism. The overexpression of the Bcl-2 family genes and the activation of the Fas/FasL pathway triggered downstream caspase cascade and caused reactive oxygen species signaling-mediated apoptosis/necrosis. To the best of our knowledge, it was the first report that the exposure to low-molecular-weight phthalate esters potentially triggered blood immunotoxicity. The result and underlying mechanisms can provide an essential basis for understanding phthalate ester toxicity and usage regulation.
AB - Dimethyl phthalate (DMP), a low-molecular-weight phthalate ester, exists in ectoparasiticides, plastics, and insect repellants, and has been linked to neurotoxic, reproductive, and endocrine disruptive responses. However, its blood immunotoxic effects and mechanism are still poorly understood. In this study, rats were exposed to gradient concentrations of DMP through intragastric administration to assess the blood immunotoxic effects in the combined assay of biomarker, cytometry, and transcriptomics. DMP treatment altered the redox status of rats, thus causing oxidative damage. Significantly decreased blood cell counts and disordered antibody and cytokine secretion were observed in treated rats, suggesting the suppressed immune defense and destructed inflammatory regulation. Flow cytometry showed that in lymphocytes, especially CD3+CD4+ T cells, the occurrence of apoptosis/necrosis was positively related to DMP exposure level. Transcriptomics revealed an oxidative stress-related mechanism. The overexpression of the Bcl-2 family genes and the activation of the Fas/FasL pathway triggered downstream caspase cascade and caused reactive oxygen species signaling-mediated apoptosis/necrosis. To the best of our knowledge, it was the first report that the exposure to low-molecular-weight phthalate esters potentially triggered blood immunotoxicity. The result and underlying mechanisms can provide an essential basis for understanding phthalate ester toxicity and usage regulation.
KW - Dimethyl phthalate
KW - Immunotoxicity
KW - Phthalate ester
KW - Transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85130892202&partnerID=8YFLogxK
U2 - 10.1016/j.scitotenv.2022.156047
DO - 10.1016/j.scitotenv.2022.156047
M3 - Journal article
C2 - 35598668
AN - SCOPUS:85130892202
SN - 0048-9697
VL - 838
JO - Science of the Total Environment
JF - Science of the Total Environment
M1 - 156047
ER -