Diethyl phthalates (DEPs) are notorious for their high potential toxicity in endocrinological and reproduction systems in humans and animals. In this study, we investigated the toxic effects of
DEP on human
lipoproteins, macrophages, and zebrafish embryos. Treatment of human
high-density lipoprotein (HDL) with
DEP caused oxidation, aggregation, and degradation of
lipoproteins.
DEP treatment promoted foam cell formation via accelerated phagocytosis of
LDL by macrophages as well as exacerbated cellular senescence in human dermal fibroblasts. Injection of
DEP (final 5 μM and 10 μM) into zebrafish embryos caused severe
embryo death and slower developmental speed. Exposure of zebrafish embryos to water containing
DEP (final 11 and 22 ppm) caused early embryonic death along with the increased oxidized products and impairment of skeletal development. Adult zebrafish exposed to water containing
DEP (final 11 and 22 ppm) for 4 weeks showed severe loss of
body weight under both normal diet (ND) and high
cholesterol diet (HCD) conditions. ND and HCD groups showed 59% and 49% reduction of plasma total
cholesterol (TC), respectively. Serum levels of hepatic
inflammation enzymes along with
fatty liver changes were significantly elevated by
DEP exposure. In conclusion,
DEP showed strong pro-atherogenic and pro-senescence effects via severe
lipoprotein modification in human cells.
DEP caused impairment of embryonic development and severe loss of
body weight, hypolipidemia, and
fatty liver changes in zebrafish.