Di(2-ethylhexyl) phthalate (DEHP) is widely used and has been implicated in hepatotoxicity, although the mechanism is unclear. Here, we investigated the effect of DEHP on hepatic cholesterol metabolism in SD rats exposed to 0 and 300 mg/kg/day DEHP for 12 weeks. An RNA-Seq analysis was performed to describe the hepatic responses to long-term DEHP exposure in combination with serological and oxidative stress parameter measurements. DEHP increased the serum levels of total cholesterol (TC), high-density lipoprotein (HDL), and alanine transaminase (ALT). Moreover, DEHP increased the content of malondialdehyde (MDA) and decreased antioxidant enzyme activities in the liver. Transcriptomic results revealed that DEHP dramatically changed the cholesterol metabolism pathway and oxidation-reduction process and depressed gene expression involved in cholesterol efflux and monooxygenase activity. Total antioxidant capacity (T-AOC) positively correlated with Abcg5 and Abcg8. Overall, this study showed the mechanisms underlying hepatotoxicity caused by DEHP, providing new insights into understanding DEHP poisoning.

邻苯二甲酸二（2-乙基己基）酯 (DEHP) 被广泛使用并与肝毒性有关，但其机制尚不清楚。在这里，我们研究了 DEHP 对暴露于 0 和 300 mg/kg/天 DEHP 12 周的 SD 大鼠肝脏胆固醇代谢的影响。进行 RNA-Seq 分析以描述肝脏对长期 DEHP 暴露的反应，并结合血清学和氧化应激参数测量。DEHP 增加了总胆固醇 (TC)、高密度脂蛋白 (HDL) 和丙氨酸转氨酶 (ALT) 的血清水平。此外，DEHP 增加了丙二醛 (MDA) 的含量并降低了肝脏中的抗氧化酶活性。转录组学结果表明，DEHP 显着改变了胆固醇代谢途径和氧化还原过程，并降低了与胆固醇流出和单加氧酶活性相关的基因表达。总抗氧化能力（T-AOC）与Abcg5和Abcg8。总体而言，这项研究揭示了 DEHP 引起肝毒性的潜在机制，为理解 DEHP 中毒提供了新的见解。