Korean J Intern Med.  2018 May;33(3):568-576. 10.3904/kjim.2016.131.

Effects of colchicine on renal fibrosis and apoptosis in obstructed kidneys

Affiliations
  • 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. jshan@snu.ac.kr
  • 2Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
  • 3Department of Internal Medicine, Hallym University Hangang Sacred Heart Hospital, Seoul, Korea.
  • 4Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea.

Abstract

BACKGROUND/AIMS
Colchicine is an established drug for microtubule stabilization that may reduce tissue injury. No data were available that its effects may depend on the dosage of colchicine. We investigated the anti-fibrotic and apoptotic effects of various dose of colchicine in a unilateral ureteral obstruction (UUO) model.
METHODS
Thirty-six Sprague-Dawley rats were randomly assigned into six groups. Two sham groups were divided into a vehicle-treated or colchicine-treated group (100 μg/kg/day). Four UUO groups were treated with either vehicle or three different doses of colchicine for 7 days (30, 60, and 100 μg/kg/day, intraperitoneally). All of the animals were sacrificed on day 7.
RESULTS
Colchicine treatment diminished acetylated α-tubulin and tumor growth factor-β immunoreactivities in the cortical area of the 7-day obstructed kidneys, which was in dose dependent manner. Colchicine attenuated tubulointerstitial damage and apoptosis in both cortical and medullary area, and beneficial effects of colchicine therapy were dramatically shown at the higher dosage of colchicine. The expression levels of cleaved caspase-3, ED-1, and fibronectin were decreased in UUO animals.
CONCLUSIONS
We found that the proper dosage of colchicine may have anti-fibrotic and anti-apoptotic effects in obstructed kidneys. For clinical applications, an optimal dose of colchicine should be evaluated to maximize the prevention of renal disease progression.

Keyword

Colchicine; Kidney; Microtubules; Ureteral obstruction

MeSH Terms

Animals
Apoptosis*
Caspase 3
Colchicine*
Disease Progression
Fibronectins
Fibrosis*
Kidney*
Microtubules
Rats, Sprague-Dawley
Ureteral Obstruction
Caspase 3
Colchicine
Fibronectins
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