Your browser doesn't support javascript.
loading
Novel cystine ester mimics for the treatment of cystinuria-induced urolithiasis in a knockout mouse model.
Sahota, Amrik; Parihar, Jaspreet S; Capaccione, Kathleen M; Yang, Min; Noll, Kelsey; Gordon, Derek; Reimer, David; Yang, Ill; Buckley, Brian T; Polunas, Marianne; Reuhl, Kenneth R; Lewis, Matthew R; Ward, Michael D; Goldfarb, David S; Tischfield, Jay A.
Afiliación
  • Sahota A; Department of Genetics, Rutgers University, Piscataway, NJ. Electronic address: sahota@biology.rutgers.edu.
  • Parihar JS; Division of Urology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ.
  • Capaccione KM; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ.
  • Yang M; Department of Genetics, Rutgers University, Piscataway, NJ.
  • Noll K; Department of Genetics, Rutgers University, Piscataway, NJ.
  • Gordon D; Department of Genetics, Rutgers University, Piscataway, NJ.
  • Reimer D; Laboratory Animal Services, Rutgers University, Piscataway, NJ.
  • Yang I; Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ.
  • Buckley BT; Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ.
  • Polunas M; Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ.
  • Reuhl KR; Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ.
  • Lewis MR; Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
  • Ward MD; Department of Chemistry, New York University, New York, NY.
  • Goldfarb DS; Nephrology Division, New York University Langone Medical Center, New York, NY.
  • Tischfield JA; Department of Genetics, Rutgers University, Piscataway, NJ.
Urology ; 84(5): 1249.e9-15, 2014 Nov.
Article en En | MEDLINE | ID: mdl-25443947
OBJECTIVE: To assess the effectiveness of l-cystine dimethyl ester (CDME), an inhibitor of cystine crystal growth, for the treatment of cystine urolithiasis in an Slc3a1 knockout mouse model of cystinuria. MATERIALS AND METHODS: CDME (200 µg per mouse) or water was delivered by gavage daily for 4 weeks. Higher doses by gavage or in the water supply were administered to assess organ toxicity. Urinary amino acids and cystine stones were analyzed to assess drug efficacy using several analytical methods. RESULTS: Treatment with CDME led to a significant decrease in stone size compared with that of the water group (P = .0002), but the number of stones was greater (P = .005). The change in stone size distribution between the 2 groups was evident by micro computed tomography. Overall, cystine excretion in urine was the same between the 2 groups (P = .23), indicating that CDME did not interfere with cystine metabolism. Scanning electron microscopy analysis of cystine stones from the CDME group demonstrated a change in crystal habit, with numerous small crystals. l-cysteine methyl ester was detected by ultra-performance liquid chromatography-mass spectrometer in stones from the CDME group only, indicating that a CDME metabolite was incorporated into the crystal structure. No pathologic changes were observed at the doses tested. CONCLUSION: These data demonstrate that CDME promotes formation of small stones but does not prevent stone formation, consistent with the hypothesis that CDME inhibits cystine crystal growth. Combined with the lack of observed adverse effects, our findings support the use of CDME as a viable treatment for cystine urolithiasis.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cistina / Cistinuria / Urolitiasis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Urology Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cistina / Cistinuria / Urolitiasis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Urology Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos