LP533401 restores bone health in 5/6 nephrectomized rats by a decrease of gut-derived serotonin and regulation of serum phosphate through the inhibition of phosphate co-transporters expression in the kidneys

LP533401 is an orally bioavailable small molecule that inhibits tryptophan hydroxylase-1, an enzyme responsible for the synthesis of gut-derived serotonin (GDS). Recently, we showed that increased GDS in rats with chronic kidney disease (CKD) affected bone strength and metabolism. We tested the hypothesis that treatment with LP533401 could reverse CKD-induced bone loss in uremia. Sixteen weeks after 5/6 nephrectomy, rats were randomized into untreated (CKD), treated with vehicle (VEH) and LP533401 at a dose of 30 or 100  mg/kg daily for 8 weeks.

Source: Bone - May 21, 2018 Category: Orthopaedics Authors: Dariusz Pawlak, Beata Znorko, Bartlomiej Kalaska, Tomasz Domaniewski, Rados ław Zawadzki, Paweł Lipowicz, Michał Doroszko, Urszula Łebkowska, Piotr Grabowski, Krystyna Pawlak Tags: Full Length Article Source Type: research