| DOI: 10.29090/psa.2026.02.25.8814 | Pharm Sci Asia 2026; 53(2), 112-121 |
Ivermectin ameliorates cyst progression in polycystic kidney disease rats and renal cell-derived cysts via suppression of chloride secretionKanlayanee Tonum1, Nipitpon Srimai2, Sunhapas Soodvilai2*
1 Department of Physiology, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand
2
Research Center of Transporter Protein for Medical Innovation, Department of Physiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
Polycystic kidney disease (PKD) is a genetic disorder characterized by the growth of numerous fluid-filled cysts in the kidneys. Ivermectin is an antiparasitic drug that has been reported to function as an agonist of the farnesoid X receptor (FXR). Activation of FXR has previously been shown to attenuate cyst progression. In the present study, we evaluated the pharmacological effects of ivermectin on renal cyst progression in vivo in a rat model of PKD and in vitro in renal cell-derived cysts. Daily subcutaneous administration of ivermectin (0.5 mg/kg body weight) for 12 weeks significantly reduced the kidney weight–to–body weight ratio and improved renal function in PKD rats compared with vehicle-treated controls. In addition, treatment with 2 µM ivermectin significantly inhibited Madin–Darby canine kidney (MDCK) cell-derived cyst formation by 31 ± 5.3% compared to vehicle-treatment. These effects were associated with suppressed cell proliferation and reduced phosphorylation of extracellular signal-regulated kinases (ERK)1/2. In addition, ivermectin significantly attenuated in vitro cyst growth by 13 ± 3.0% compared with control. This inhibitory effect on cyst growth was associated with reduced cystic fibrosis transmembrane conductance regulator (CFTR)– and TMEM16A-mediated chloride secretion by 36 ± 3.1% and 12 ± 2.8%, respectively, compared with control. Collectively, these findings demonstrate that ivermectin inhibits renal cyst progression both in vivo and in vitro, supporting its potential as a pharmacological modulator of cyst growth in PKD.
Keyword:
Ivermectin; Repurposing drug; Chloride secretion; Kidney; Farnesoid X receptor
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