Alessandro Mengozzi1, Fabrizia Carli2, Letizia Guiducci2, Federico Parolini1, Edoardo Biancalana1, Amalia Gastaldelli3, Anna Solini4. 1. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. 2. Institute of Clinical Physiology, National Research Council, Pisa, Italy. 3. Institute of Clinical Physiology, National Research Council, Pisa, Italy. Electronic address: amalia@ifc.cnr.it. 4. Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. Electronic address: anna.solini@med.unipi.it.
Abstract
OBJECTIVE: 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. DESIGN AND METHODS: 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). RESULTS: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. CONCLUSIONS: 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.
RCT Entities:
OBJECTIVE: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. DESIGN AND METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
Authors: Jerrold J Heindel; Sarah Howard; Keren Agay-Shay; Juan P Arrebola; Karine Audouze; Patrick J Babin; Robert Barouki; Amita Bansal; Etienne Blanc; Matthew C Cave; Saurabh Chatterjee; Nicolas Chevalier; Mahua Choudhury; David Collier; Lisa Connolly; Xavier Coumoul; Gabriella Garruti; Michael Gilbertson; Lori A Hoepner; Alison C Holloway; George Howell; Christopher D Kassotis; Mathew K Kay; Min Ji Kim; Dominique Lagadic-Gossmann; Sophie Langouet; Antoine Legrand; Zhuorui Li; Helene Le Mentec; Lars Lind; P Monica Lind; Robert H Lustig; Corinne Martin-Chouly; Vesna Munic Kos; Normand Podechard; Troy A Roepke; Robert M Sargis; Anne Starling; Craig R Tomlinson; Charbel Touma; Jan Vondracek; Frederick Vom Saal; Bruce Blumberg Journal: Biochem Pharmacol Date: 2022-04-05 Impact factor: 6.100