Effect of twice-daily oral administration of a chondroitin sulfate–containing supplement on urine chondroitin sulfate concentrations in dogs

Michael W. Wood 1Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53704.

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 DVM, PhD
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Gregory A. Barrett-Wilt 2Mass Spectrometry Facility, Biotechnology Center, University of Wisconsin-Madison, Madison, WI 53706.
1Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53704.
2Mass Spectrometry Facility, Biotechnology Center, University of Wisconsin-Madison, Madison, WI 53706.

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Abstract

OBJECTIVE

To quantify the magnitude and duration of changes in urine chondroitin sulfate concentration (uCS) as a result of oral administration of a chondroitin sulfate–containing supplement in dogs.

ANIMALS

8 healthy privately owned dogs.

PROCEDURES

A urine sample was collected from each dog via cystocentesis on day 1; free-catch midstream urine samples were collected once daily on days 2 through 5. Pretreatment uCS was established from those samples. Each dog then received a chondroitin sulfate–containing supplement (20 to 30 mg/kg, PO, q 12 h) for 8 days (on days 7 through 14). Urine samples were collected on days 8 through 12 and day 15. For each sample, uCS was quantified by liquid chromatography–tandem mass spectrometry. Variable urine concentration was accounted for by dividing the uCS by urine creatinine concentration (uCrea) to determine the uCS:uCrea ratio. Pretreatment uCS:uCrea ratios were compared with treatment uCS:uCrea ratios to calculate the fold change in uCS after supplement administration.

RESULTS

Among the study dogs, oral administration of the chondroitin sulfate–containing supplement resulted in a 1.9-fold increase in the median uCS:uCrea ratio. Data obtained on days 8 through 12 and day 15 indicated that the daily increase in uCS remained consistent and was not additive.

CONCLUSIONS AND CLINICAL RELEVANCE

Results indicated that oral administration of supplemental chondroitin sulfate to dogs modestly increased uCS within 24 hours; however, subsequent supplement administration did not have an additive effect. A potential therapeutic benefit of persistently increased uCS in preventing recurrent urinary tract infections in dogs warrants investigation.

Abstract

OBJECTIVE

To quantify the magnitude and duration of changes in urine chondroitin sulfate concentration (uCS) as a result of oral administration of a chondroitin sulfate–containing supplement in dogs.

ANIMALS

8 healthy privately owned dogs.

PROCEDURES

A urine sample was collected from each dog via cystocentesis on day 1; free-catch midstream urine samples were collected once daily on days 2 through 5. Pretreatment uCS was established from those samples. Each dog then received a chondroitin sulfate–containing supplement (20 to 30 mg/kg, PO, q 12 h) for 8 days (on days 7 through 14). Urine samples were collected on days 8 through 12 and day 15. For each sample, uCS was quantified by liquid chromatography–tandem mass spectrometry. Variable urine concentration was accounted for by dividing the uCS by urine creatinine concentration (uCrea) to determine the uCS:uCrea ratio. Pretreatment uCS:uCrea ratios were compared with treatment uCS:uCrea ratios to calculate the fold change in uCS after supplement administration.

RESULTS

Among the study dogs, oral administration of the chondroitin sulfate–containing supplement resulted in a 1.9-fold increase in the median uCS:uCrea ratio. Data obtained on days 8 through 12 and day 15 indicated that the daily increase in uCS remained consistent and was not additive.

CONCLUSIONS AND CLINICAL RELEVANCE

Results indicated that oral administration of supplemental chondroitin sulfate to dogs modestly increased uCS within 24 hours; however, subsequent supplement administration did not have an additive effect. A potential therapeutic benefit of persistently increased uCS in preventing recurrent urinary tract infections in dogs warrants investigation.

Contributor Notes

Address correspondence to Dr. Wood (mwood5@wisc.edu).
  • 1. Ruggieri MR, Hanno PM, Samadzadeh S, et al. Heparin inhibition of increased bacterial adherence following overdistension, ischemia and partial outlet obstruction of the rabbit urinary bladder. J Urol 1986;136:132135.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. Hurst RE, Rhodes SW, Adamson PB, et al. Functional and structural characteristics of the glycosaminoglycans of the bladder luminal surface. J Urol 1987;138:433437.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Janssen DA, van Wijk XM, Jansen KC, et al. The distribution and function of chondroitin sulfate and other sulfated glycosaminoglycans in the human bladder and their contribution to the protective bladder barrier. J Urol 2013;189:336342.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Parsons CL. Prevention of urinary-tract infection by the exogenous glycosaminoglycan sodium pentosanpolysulfate. J Urol 1982;127:167169.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Tay H, Parsons CL, Stein PC. Electrophysiologic monitoring of the effects of soluble virulence factors produced by Escherichia coli infection in urine. Urology 1996;48:389392.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Parsons CL. The role of the urinary epithelium in the pathogenesis of interstitial cystitis/prostatitis/urethritis. Urology 2007;69:916.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Keay SK, Zhang CO, Shoenfelt, et al. Sensitivity and specificity of antiproliferative factor, heparin-binding epidermal growth factor–like growth factor, and epidermal growth factor as urine markers for interstitial cystitis. Urology 2001;57:914.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Parsons CL. The role of a leaky epithelium and potassium in the generation of bladder symptoms in interstitial cystitis/overactive bladder, urethral syndrome, prostatitis and gynaecological chronic pelvic pain. BJU Int 2011;107:370375.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Cicione A, Cantiello F, Ucciero G, et al. Restoring the glycosaminoglycans layer in recurrent cystitis: experimental and clinical foundations. Int J Urol 2014;21:763768.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Hauser PJ, VanGordon SB, Seavey J, et al. Abnormalities in expression of structural, barrier and differentiation related proteins, and chondroitin sulfate in feline and human interstitial cystitis. J Urol 2015;194:571577.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Hurst RE, Roy JB, Min KW, et al. A deficit of chondroitin sulfate proteoglycans on the bladder uroepithelium in interstitial cystitis. Urology 1996;48:817821.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Siracusano S, Cucchi A, Ciciliato S, et al. Urinary levels of glycosaminoglycans in patients with idiopathic detrusor overactivity. Int Urogynecol J Pelvic Floor Dysfunc 2009;20:14771480.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13. Schwalenberg T, Berger FP, Horn LC, et al. Intravesical glycosaminoglycan replacement with chondroitin sulphate (Gepan instill) in patients with chronic radiotherapy- or chemotherapy-associated cystitis. Clin Drug Investig 2015;35:505512.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. Parsons CL, Stauffer C, Schmidt JD. Impairment of antibacterial effect of bladder surface mucin by protamine sulfate. J Infect Dis 1981;144:180.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. Parsons CL, Mulholland SG. Bladder surface mucin. Its antibacterial effect against various bacterial species. Am J Pathol 1978;93:423432.

    • Search Google Scholar
    • Export Citation
  • 16. Parsons CL, Mulholland SG, Anwar H. Antibacterial activity of bladder surface mucin duplicated by exogenous glycosaminoglycan (heparin). Infect Immun 1979;24:552557.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Lee DG, Cho JJ, Park HK, et al. Preventive effects of hyaluronic acid on Escherichia coli-induced urinary tract infection in rat. Urology 2010;75:949954.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Constantinides C, Manousakas T, Nikolopoulos P, et al. Prevention of recurrent bacterial cystitis by intravesical administration of hyaluronic acid: a pilot study. BJU Int 2004;93:12621266.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Lipovac M, Kurz C, Reithmayr F, et al. Prevention of recurrent bacterial urinary tract infections by intravesical instillation of hyaluronic acid. Int J Gynaecol Obstet 2007;96:192195.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20. Torella M, Schettino MT, Salvatore S, et al. Intravesical therapy in recurrent cystitis: a multi-center experience. J Infect Chemother 2013;19:920925.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. De Vita D, Antell H, Giordano S. Effectiveness of intravesical hyaluronic acid with or without chondroitin sulfate for recurrent bacterial cystitis in adult women: a meta-analysis. Int Urogynecol J 2013;24:545552.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Ciani O, Arendsen E, Romancik M, et al. Intravesical administration of combined hyaluronic acid (HA) and chondroitin sulfate (CS) for the treatment of female recurrent urinary tract infections: a European multicentre nested case-control study. BMJ Open 2016;6:e009669.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Damiano R, Quarto G, Bava I, et al. Prevention of recurrent urinary tract infections by intravesical administration of hyaluronic acid and chondroitin sulphate: a placebo-controlled randomised trial. Eur Urol 2011;59:645651.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24. Barthe L, Woodley J, Lavit M, et al. In vitro intestinal degradation and absorption of chondroitin sulfate, a glycosaminoglycan drug. Arzneimittelforschung 2004;54:286292.

    • Search Google Scholar
    • Export Citation
  • 25. Conte A, Volpi N, Palmieri L, et al. Biochemical and pharmacokinetic aspects of oral treatment with chondroitin sulfate. Arzneimittelforschung 1995;45:918925.

    • Search Google Scholar
    • Export Citation
  • 26. Lamari FN, Theocharis AD, Asimakopoulou AP, et al. Metabolism and biochemical/physiological roles of chondroitin sulfates: analysis of endogenous and supplemental chondroitin sulfates in blood circulation. Biomed Chromatogr 2006;20:539550.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27. Conte A, Palmieri L, Segnini D, et al. Metabolic-fate of partially depolymerized chondroitin sulfate administered to the rat. Drugs Exp Clin Res 1991;17:2733.

    • Search Google Scholar
    • Export Citation
  • 28. Adebowale A, Du J, Liang Z, et al. The bioavailability and pharmacokinetics of glucosamine hydrochloride and low molecular weight chondroitin sulfate after single and multiple doses to Beagle dogs. Biopharm Drug Dispos 2002;23:217225.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Zhang H, Young SP, Auray-Blais C, et al. Analysis of glycosaminoglycans in cerebrospinal fluid from patients with mucopolysaccharidoses by isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry. Clin Chem 2011;57:10051012.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Zhang H, Young SP, Millington DS. Quantification of glycosaminoglycans in urine by isotope-dilution liquid chromatography-electrospray ionization tandem mass spectrometry. Curr Protoc Hum Genet 2013;76:17.12.1–17.12.14.

    • Search Google Scholar
    • Export Citation
  • 31. Grant DC, Forrester SD, Panciera DL, et al. Measurement of urinary glycosaminoglycans in dogs. Am J Vet Res 2006;67:5155.

  • 32. Plumb D. Glucosamine/chondroitin sulfate. In: Plumb's veterinary drug handbook. 6th ed. Ames, Iowa: Wiley-Blackwell, 2008;429–431.

    • Search Google Scholar
    • Export Citation
  • 33. De Vita D, Giordano S. Effectiveness of intravesical hyaluronic acid/chondroitin sulfate in recurrent bacterial cystitis: a randomized study. Int Urogynecol J 2012;23:17071713.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34. Torella M, Del Deo F, Grimaldi A, et al. Efficacy of an orally administered combination of hyaluronic acid, chondroitin sulfate, curcumin and quercetin for the prevention of recurrent urinary tract infections in postmenopausal women. Eur J Obstet Gynecol Reprod Biol 2016;207:125128.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35. Cervigni M, Natale F, Nasta L, et al. A combined intravesical therapy with hyaluronic acid and chondroitin for refractory painful bladder syndrome/interstitial cystitis. Int Urogynecol J Pelvic Floor Dysfunct 2008;19:943947.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36. Kyker KD, Coffman J, Hurst RE. Exogenous glycosaminoglycans coat damaged bladder surfaces in experimentally damaged mouse bladder. BMC Urol 2005;5:4.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37. Hauser PJ, Buethe DA, Califano J, et al. Restoring barrier function to acid damaged bladder by intravesical chondroitin sulfate. J Urol 2009;182:24772482.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38. Sadhukhan PC, Tchetgen MB, Rackley RR, et al. Sodium pentosan polysulfate reduces urothelial responses to inflammatory stimuli via an indirect mechanism. J Urol 2002;168:289292.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39. Boucher WS, Letourneau R, Huang M, et al. Intravesical sodium hyaluronate inhibits the rat urinary mast cell mediator increase triggered by acute immobilization stress. J Urol 2002;167:380384.

    • Crossref
    • Search Google Scholar
    • Export Citation

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