Effects of combined administration of rapamycin, tolvaptan and AEZ-131 on progression of polycystic disease in PCK rats. (Articolo in rivista)

Type
Label
  • Effects of combined administration of rapamycin, tolvaptan and AEZ-131 on progression of polycystic disease in PCK rats. (Articolo in rivista) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Alternative label
  • Sabbatini M, Russo L, Cappellaio F, Troncone G, Bellevicine C, De Falco V, Buonocore P, Riccio E, Bisesti V, Federico S, Pisani A. (2014)
    Effects of combined administration of rapamycin, tolvaptan and AEZ-131 on progression of polycystic disease in PCK rats.
    in American journal of physiology. Renal physiology.
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Sabbatini M, Russo L, Cappellaio F, Troncone G, Bellevicine C, De Falco V, Buonocore P, Riccio E, Bisesti V, Federico S, Pisani A. (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • University Federico II, Naples, Italy. (literal)
Titolo
  • Effects of combined administration of rapamycin, tolvaptan and AEZ-131 on progression of polycystic disease in PCK rats. (literal)
Abstract
  • Both experimental and clinical studies suggest that any potential treatment of polycystic kidney disease should start early and last for a long time to be effective, with unavoidable side reactions and considerable costs. The aim of the present study was to test how low-doses of Rapamycin (RAPA, 0.15 mg/Kg/4 days a week i.p.), Tolvaptan (TOLV, 0.005% in the diet) or AEZ131, a novel ERK inhibitor (AEZ, 30 mg/kg/thrice a week by gavage), alone and in association, affect the progression of polycystic renal disease in PCK rats. Rats were treated for 8 weeks, starting at 4-6 weeks of age. The efficacy of low-doses of such drugs in inhibiting their respective targets was confirmed by immunoblotting studies. Compared to control rats, RAPA determined a significant reduction in cyst volume density (CVD, -19% vs CON), numerically similar in TOLV treated rats (-18%, NS), whereas AEZ was not effective. RAPA+TOLV determined a significantly lower CVD (-49% vs CON), associated with a striking decrease in CREB phosphorylation, and similar data were detected in RAPA+AEZ rats (-42%), whereas the association TOLV+AEZ had virtually no effect. RAPA administration significantly lessened body weight gain, whereas TOLV determined mild increase in diuresis and a significant increase in cAMP urinary excretion. Histological data of tubular proliferation were in full agreement with the data of CVD. In conclusion, this study demonstrates that the association of low-doses of RAPA, TOLV and AEZ slows the progression of PKD with limited side effects, suggesting the use of combined therapies also in clinical trials. (literal)
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