Lee Hyeon-Jeong, Jin Jonghwa, Seo Yoondam, Kang Inseon, Son Junghyun, Yi Eugene C, Min Hophil
Doping Control Center, Korea Institute of Science and Technology, Seongbuk-gu, Seoul 02792, Republic of Korea.
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Jongno-gu, Seoul 03080, Republic of Korea.
Toxics. 2023 Sep 20;11(9):794. doi: 10.3390/toxics11090794.
Di-(2-Ethylhexyl) phthalate (DEHP) is a prevalent environmental endocrine disruptor that affects homeostasis, reproduction, and developmental processes. The effects of DEHP have been shown to differ based on sex and sexual maturity. This study examines the metabolic profiles of mature adult rats from both sexes, aged 10 weeks, and adolescent female rats, aged 6 weeks, following a single 5 mg/kg of body weight DEHP oral administration. An untargeted metabolomic analysis was conducted on urine samples collected at multiple times to discern potential sex- and maturity-specific DEHP toxicities. Various multivariate statistical analyses were employed to identify the relevant metabolites. The findings revealed disruptions to the steroid hormone and primary bile acid biosynthesis. Notably, DEHP exposure increased hyocholic, muricholic, and ketodeoxycholic acids in male rats. Moreover, DEHP exposure was linked to heart, liver, and kidney damage, as indicated by increased plasma GOT1 levels when compared to the levels before DEHP exposure. This study provides detailed insights into the unique mechanisms triggered by DEHP exposure concerning sex and sexual maturity, emphasizing significant distinctions in lipid metabolic profiles across the different groups. This study results deepens our understanding of the health risks linked to DEHP, informing future risk assessments and policy decisions.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种普遍存在的环境内分泌干扰物，会影响体内平衡、生殖和发育过程。已表明DEHP的影响因性别和性成熟度而异。本研究考察了10周龄的成年雌雄大鼠以及6周龄的青春期雌性大鼠在单次口服5mg/kg体重DEHP后的代谢谱。对多次采集的尿液样本进行非靶向代谢组学分析，以识别潜在的性别和成熟度特异性DEHP毒性。采用各种多元统计分析来鉴定相关代谢物。研究结果揭示了类固醇激素和初级胆汁酸生物合成受到干扰。值得注意的是，DEHP暴露使雄性大鼠的猪去氧胆酸、鼠胆酸和酮脱氧胆酸增加。此外，与DEHP暴露前的水平相比，血浆谷草转氨酶1（GOT1）水平升高表明DEHP暴露与心脏、肝脏和肾脏损伤有关。本研究详细深入地了解了DEHP暴露引发的与性别和性成熟相关的独特机制，强调了不同组之间脂质代谢谱的显著差异。本研究结果加深了我们对与DEHP相关的健康风险的理解，为未来的风险评估和政策决策提供了依据。
