Dimethyl Phthalate Induces Blood Immunotoxicity Through Oxidative Damage And Caspase-Dependent Apoptosis

Abstract Dimethyl phthalate (DMP), a low molecular weight phthalate ester, is present in ectoparasiticides, plastics, and insect repellants, has been linked to neurotoxic, reproductive, and endocrine disruptive responses. However, its blood immunotoxic effects and mechanism remain poorly understood. In this study, rats were exposed to graded concentrations of DMP through intragastric administration to assess the blood immunotoxic effects using a combination assay of biomarker, cytometry, and transcriptomics. DMP treatment altered the redox status of rats, causing that oxidative damage. Significantly decreased blood cell counts and disordered antibody and cytokine secretion were observed, suggesting the suppressed immune defense and destructed inflammatory regulation. Flow cytometry showed for lymphocytes, especially CD3+CD4+ T cells, apoptosis/necrosis occurred positively related to DMP exposure level. Transcriptomics revealed responses that were in line with oxidative damage effects. Overexpression of the Bcl-2 family genes and activation of the Fas/FasL pathway trigger downstream caspase cascade, causing reactive oxygen species signaling mediated apoptosis/necrosis. This is the first report on immunotoxic effects of low molecular weight phthalate esters.