Halofuginone-coated urethral catheters prevent periurethral spongiofibrosis in a rat model of urethral injury

Louis S. Krane, Ilya Gorbachinsky, Joseph Sirintrapun, James J. Yoo, Anthony Atala, Steve J. Hodges

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background and Purpose: Urethral strictures are from periurethral spongiofibrosis that develops as a result of urethral trauma, disease, or iatrogenic injury. The spongy tissue that surrounds the strictured urethra has an altered ratio of collagen, with increased collagen type I relative to type III. We evaluated the ability of a urethral catheter that was coated with halofuginone (HF), a potent type I collagen inhibitor, to prevent spongiofibrosis formation in a rat model. Materials and Methods: HF was coated on silicone catheters and release kinetics were measured. Success of impregnation was evaluated with scanning electron microscopy, serial weights, and drug elution data. Urethral strictures were induced in rats using electrocautery. Half the animals had placement of an HF-coated catheter while the others had uncoated silicone controls. Animals were sacrificed at predetermined time points, and urethral tissue was either processed for staining with Masson trichrome and anti-alpha-1 collagen or digested to determine HF concentration. Serum drug levels were also determined in treated animals. Slides were graded by a pathologist who was blinded to treatment to determine collagen deposition. Results: HF was coated successfully on silicone catheters. Local urethral concentration of HF was tenfold higher than serum concentration in treated rats. Animals with HF-coated catheters had no new type I collagen deposition after urethral injury. Control animals had increased periurethral collagen type I deposition, typical of urethral stricture formation. Conclusions: HF can be coated successfully on silicone catheters. HF successfully inhibits periurethral type I collagen deposition after urethral injury. This may become an important therapy to prevent urethral stricture formation or recurrence after endoscopic therapy.

Original languageEnglish
Pages (from-to)107-112
Number of pages6
JournalJournal of Endourology
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

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Urinary Catheters
Urethral Stricture
Collagen Type I
Wounds and Injuries
Silicones
Catheters
Collagen
Urethral Diseases
halofuginone
Electrocoagulation
Urethra
Serum
Pharmaceutical Preparations
Electron Scanning Microscopy
Therapeutics
Staining and Labeling
Weights and Measures
Recurrence

ASJC Scopus subject areas

  • Urology

Cite this

Krane, L. S., Gorbachinsky, I., Sirintrapun, J., Yoo, J. J., Atala, A., & Hodges, S. J. (2011). Halofuginone-coated urethral catheters prevent periurethral spongiofibrosis in a rat model of urethral injury. Journal of Endourology, 25(1), 107-112. https://doi.org/10.1089/end.2010.0514

Halofuginone-coated urethral catheters prevent periurethral spongiofibrosis in a rat model of urethral injury. / Krane, Louis S.; Gorbachinsky, Ilya; Sirintrapun, Joseph; Yoo, James J.; Atala, Anthony; Hodges, Steve J.

In: Journal of Endourology, Vol. 25, No. 1, 01.01.2011, p. 107-112.

Research output: Contribution to journalArticle

Krane, LS, Gorbachinsky, I, Sirintrapun, J, Yoo, JJ, Atala, A & Hodges, SJ 2011, 'Halofuginone-coated urethral catheters prevent periurethral spongiofibrosis in a rat model of urethral injury', Journal of Endourology, vol. 25, no. 1, pp. 107-112. https://doi.org/10.1089/end.2010.0514
Krane, Louis S. ; Gorbachinsky, Ilya ; Sirintrapun, Joseph ; Yoo, James J. ; Atala, Anthony ; Hodges, Steve J. / Halofuginone-coated urethral catheters prevent periurethral spongiofibrosis in a rat model of urethral injury. In: Journal of Endourology. 2011 ; Vol. 25, No. 1. pp. 107-112.
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