TOM70-Mitochondrial Pathway Reduction Mediates DEHP-Induced Neuroinflammation in Mice

Di(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer in polyvinyl chloride (PVC) products. The translocase of the outer mitochondrial membrane 70 (TOM70) mediates the import of various proteins into the mitochondria. This study aims to investigate the influence of DEHP on the nervous system and elucidate the potential protective role of TOM70 in microglia. Mice were administered DEHP at doses of 0, 50, 200, or 500 mg/kg for 28 days. DEHP reduced cortical cell counts, lowered cell density, and caused cell swelling, nuclear pyknosis, and mitochondrial damage in brain cells, with effects exacerbated in the D200 group and most severe in the D500 group. Further investigation revealed that DEHP inhibited TOM70 expression and suppressed the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. These findings suggest that TOM70 may be a potential target against DEHP-induced microglial neuroinflammation via mitochondrial damage. This study provides new insights into therapeutic strategies for tackling neurodegenerative diseases.