Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Institute of Clinical Physiology, National Research Council, Pisa, Italy.
Environ Res. 2021 Jan;192:110316. doi: 10.1016/j.envres.2020.110316. Epub 2020 Oct 13.
Phthalates are non-persistent pollutants related to impaired metabolism and high cardiovascular risk. Their toxic metabolites are eliminated through urine and feces. Prevention policies are considered by the governments, although no therapeutic strategy to facilitate their elimination from the human body has been proposed so far. Aim of the present study was to verify, for the first time in humans, whether diuretics might be able to enhance phthalates' toxic metabolites urinary output.
We conducted a two-armed, parallel-design, randomized clinical trial. Thirty patients with type 2 diabetes and hypertension received a four week-treatment with Dapagliflozin 10 mg or Hydrochlorothiazide 12.5 mg. 24-hours urine were collected to measure urinary excretion of three major 2-ethylhexyl-phthalate (DEHP) metabolites, i.e. mono 2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) and mono 2-ethyl-5-hydroxyhexyl phthalate (MEHHP).
24-h urinary excretion of DEHP and MEHP was increased (+44%, p = 0.036; +49%, p = 0.0016) while MEOHP e MEHHP showed only a positive trend (+25%, p = 0.016; +36%, p = 0.062). Irrespective of the specific treatment, induced variations of daily urinary eliminations of MEHP metabolites were related with the 24-h urinary sodium (r = 0.42, p = 0.0226) and potassium (r = 0.54, p = 0.0026) excretion. Also, DEHP and MEOHP were related to sodium (r = 0·43, p = 0.0205; r = 0·44, p = 0.0168 respectively) but not to potassium.
Urinary phthalates excretion seems to occur mainly through sodium- and potassium-related mechanisms, apparently independent from the different diuretic effect. Both thiazide diuretics and SLGT2 inhibitors are effective into the removal of phthalates metabolites from the human body, reducing the human tissues' exposure to their toxicity.
邻苯二甲酸酯是与代谢受损和心血管疾病风险升高有关的非持久性污染物。其有毒代谢物通过尿液和粪便排出。各国政府都在考虑采取预防政策，尽管迄今为止尚未提出促进其从人体中排出的治疗策略。本研究的目的是首次在人体中验证利尿剂是否能够增加邻苯二甲酸酯有毒代谢物的尿液排泄量。
我们进行了一项双臂、平行设计、随机临床试验。30 名 2 型糖尿病和高血压患者接受了为期四周的达格列净 10mg 或氢氯噻嗪 12.5mg 治疗。收集 24 小时尿液以测量三种主要 2-乙基己基邻苯二甲酸酯（DEHP）代谢物的尿排泄量，即单 2-乙基己基邻苯二甲酸酯（MEHP）、单-2-乙基-5-氧代己基邻苯二甲酸酯（MEOHP）和单-2-乙基-5-羟基己基邻苯二甲酸酯（MEHHP）。
DEHP 和 MEHP 的 24 小时尿排泄量增加（+44%，p=0.036；+49%，p=0.0016），而 MEOHP 和 MEHHP 仅呈正趋势（+25%，p=0.016；+36%，p=0.062）。无论具体治疗如何，MEHP 代谢物的每日尿液排泄量的变化均与 24 小时尿钠（r=0.42，p=0.0226）和钾（r=0.54，p=0.0026）排泄有关。此外，DEHP 和 MEOHP 与钠（r=0.43，p=0.0205；r=0.44，p=0.0168）相关，但与钾无关。
尿邻苯二甲酸酯排泄似乎主要通过钠和钾相关机制发生，显然与不同的利尿剂作用无关。噻嗪类利尿剂和 SGLT2 抑制剂均能有效去除人体中的邻苯二甲酸酯代谢物，减少人体组织接触其毒性。
