| Autor: |
Vinknes, Kathrine J., Olsen, Thomas, Zaré, Hasse Khiabani, Bastani, Nasser E., Stolt, Emma, Dahl, Anja F., Cox, Roger D., Refsum, Helga, Retterstøl, Kjetil, Åsberg, Anders, Elshorbagy, Amany |
| Předmět: |
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| Zdroj: |
Diabetes, Obesity & Metabolism; Nov2023, Vol. 25 Issue 11, p3161-3170, 10p |
| Abstrakt: |
Aim: To investigate whether mesna—sodium‐2‐mercaptoethane sulfonate) can reduce diet‐induced fat gain in mice, and to assess the safety of single ascending mesna doses in humans to find the dose associated with lowering of plasma tCys by at least 30%. Methods: C3H/HeH mice were shifted to a high‐fat diet ± mesna in drinking water; body composition was measured at weeks 0, 2 and 4. In an open, phase I, single ascending dose study, oral mesna (400, 800, 1200, 1600 mg) was administered to 17 men with overweight or obesity. Mesna and tCys concentrations were measured repeatedly for a duration of 48 hours postdosing in plasma, as well as in 24‐hour urine. Results: Compared with controls, mesna‐treated mice had lower tCys and lower estimated mean fat mass gain from baseline (week 2: 4.54 ± 0.40 vs. 6.52 ± 0.36 g; week 4: 6.95 ± 0.35 vs. 8.19 ± 0.34 g; Poverall =.002), but similar lean mass gain. In men with overweight, mesna doses of 400‐1600 mg showed dose linearity and were well tolerated. Mesna doses of 800 mg or higher decreased plasma tCys by 30% or more at nadir (4h post‐dosing). With increasing mesna dose, tCys AUC0‐12h decreased (Ptrend <.001), and urine tCys excretion increased (Ptrend =.004). Conclusions: Mesna reduces diet‐induced fat gain in mice. In men with overweight, single oral doses of mesna (800‐1600 mg) were well tolerated and lowered plasma tCys efficiently. The effect of sustained tCys‐lowering by repeated mesna administration on weight loss in humans deserves investigation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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