Chi Zhenxing, Lin Hongwei, Wang Xiaodan, Meng Xuanlin, Zhou Jieqiong, Xiang Li, Cao Guodong, Wu Pengfei, Cai Zongwei, Zhao Xingchen
School of Marine Science and Technology, Harbin Institute of Technology, Weihai, Weihai 264209, China.
School of Marine Science and Technology, Harbin Institute of Technology, Weihai, Weihai 264209, China.
Sci Total Environ. 2022 Sep 10;838(Pt 2):156047. doi: 10.1016/j.scitotenv.2022.156047. Epub 2022 May 20.
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 CD3CD4 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.
邻苯二甲酸二甲酯（DMP）是一种低分子量的邻苯二甲酸酯，存在于驱虫剂、塑料和驱蚊剂中，并与神经毒性、生殖毒性和内分泌干扰反应有关。然而，其血液免疫毒性作用及其机制仍知之甚少。在本研究中，通过灌胃给予大鼠梯度浓度的DMP，以在生物标志物、细胞计数和转录组学的联合检测中评估血液免疫毒性作用。DMP处理改变了大鼠的氧化还原状态，从而导致氧化损伤。在处理的大鼠中观察到血细胞计数显著下降以及抗体和细胞因子分泌紊乱，表明免疫防御受到抑制且炎症调节遭到破坏。流式细胞术显示，在淋巴细胞中，尤其是CD3CD4 T细胞，凋亡/坏死的发生与DMP暴露水平呈正相关。转录组学揭示了一种与氧化应激相关的机制。Bcl-2家族基因的过表达以及Fas/FasL途径的激活触发了下游半胱天冬酶级联反应，并导致活性氧信号介导的凋亡/坏死。据我们所知，这是首次报道低分子量邻苯二甲酸酯暴露可能引发血液免疫毒性。该结果及其潜在机制可为理解邻苯二甲酸酯毒性和使用监管提供重要依据。
