Long-term dietary nitrate supplementation does not reduce renal cyst growth in experimental autosomal dominant polycystic kidney disease
Zhang JQJ, Saravanabavan S, Cheng KM, Raghubanshi A, Chandra AN, Munt A, Rayner B, Zhang Y, Chau K, Wong ATY, Rangan GK
PloS one · 4 citas
Cómo se estudió
- Diseño
- Estudio en animales (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- David and Elaine Potter Foundation
- Organización sin fines de lucro
- Ian Potter Foundation
- Universidad u hospital
- Cancer Institute NSW
- Universidad u hospital
- University of Sydney
- Organización sin fines de lucro
- PKD Australia
- Gobierno
- Medical Research Council
- Gobierno
- National Health and Medical Research Council
- Universidad u hospital
- University of Sydney, Research Training Program Stipend
- Gobierno
- National Health and Medical Research Council of Australia
- Subvenciones
- National Health and Medical Research Council (1138533); National Health and Medical Research Council (1164128)
Según 9 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2021-04-22 · PLoS One · vol. 16 · número 4 · pág. e0248400
- Editorial
- Public Library of Science
- Citado
- 16 citas · más que el 89% de estudios similares · 2.3× el promedio de su campo
- Referencias
- 76 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY
- Áreas de investigación
- Genetic and Kidney Cyst Diseases · Biomedical Research and Pathophysiology · Birth, Development, and Health
- Palabras clave
- Autosomal dominant polycystic kidney disease, Polycystic kidney disease, Cyst, Nitrate, Endocrinology, Kidney disease, Kidney, Internal medicine, Medicine, Disease, Biology, Physiology, Pathology, Ecology
- MeSH
- kidney, cell line, animals, mice, inbred c57bl, dogs, humans, mice, cysts, polycystic kidney, autosomal dominant, nitrates, dietary supplements, female, male, madin darby canine kidney cells
11 autores
- Jennifer Q. J. Zhang🇦🇺The University of Sydney; Westmead Hospital; Sydney Local Health District; Westmead Institute for Medical Research; Western Sydney Local Health District
- Sayanthooran Saravanabavan🇦🇺The University of Sydney; Westmead Hospital; Sydney Local Health District; Westmead Institute for Medical Research; Western Sydney Local Health District
- Kai Cheng🇦🇺The University of Sydney; Westmead Hospital; Sydney Local Health District; Westmead Institute for Medical Research; Western Sydney Local Health District
- Aarya Raghubanshi🇦🇺The University of Sydney; Westmead Hospital; Sydney Local Health District; Westmead Institute for Medical Research; Western Sydney Local Health District
- Ashley N. Chandra🇦🇺The University of Sydney; Westmead Hospital; Sydney Local Health District; Westmead Institute for Medical Research; Western Sydney Local Health District
- Alexandra Munt🇦🇺The University of Sydney; Westmead Hospital; Sydney Local Health District; Westmead Institute for Medical Research; Western Sydney Local Health District
- Benjamin S. Rayner🇦🇺The University of Sydney; The Heart Research Institute
- Yunjia Zhang🇦🇺The University of Sydney; The Heart Research Institute
- Katrina Chau🇦🇺Camden and Campbelltown Hospitals; Blacktown & Mount Druitt Hospital; Western Sydney University
- Annette T. Y. Wong🇦🇺The University of Sydney; Westmead Hospital; Sydney Local Health District; Westmead Institute for Medical Research; Western Sydney Local Health District
- Gopala K. Rangan🇦🇺 · autor de correspondenciaThe University of Sydney; Westmead Hospital; Sydney Local Health District; Westmead Institute for Medical Research; Western Sydney Local Health District
Resumen
El texto original del estudio, en el idioma en que se publicó.
Augmentation of endogenous nitric oxide (NO) synthesis, either by the classical L-arginine-NO synthase pathway, or the recently discovered entero-salivary nitrate-nitrite-NO system, may slow the progression of autosomal dominant polycystic kidney disease (ADPKD). To test this hypothesis, the expression of NO in human ADPKD cell lines (WT 9-7, WT 9-12), and the effect of L-arginine on an in vitro model of three-dimensional cyst growth using MDCK cells, was examined. In addition, groups of homozygous Pkd1RC/RC mice (a hypomorphic genetic ortholog of ADPKD) received either low, moderate or high dose sodium nitrate (0.1, 1 or 10 mmol/kg/day), or sodium chloride (vehicle; 10 mmol/kg/day), supplemented drinking water from postnatal month 1 to 9 (n = 12 per group). In vitro, intracellular NO, as assessed by DAF-2/DA fluorescence, was reduced by >70% in human ADPKD cell lines, and L-arginine and the NO donor, sodium nitroprusside, both attenuated in vitro cyst growth by up to 18%. In contrast, in Pkd1RC/RC mice, sodium nitrate supplementation increased serum nitrate/nitrite levels by ~25-fold in the high dose group (P<0.001), but kidney enlargement and percentage cyst area was not altered, regardless of dose. In conclusion, L-arginine has mild direct efficacy on reducing renal cyst growth in vitro, whereas long-term sodium nitrate supplementation was ineffective in vivo. These data suggest that the bioconversion of dietary nitrate to NO by the entero-salivary pathway may not be sufficient to influence the progression of renal cyst growth in ADPKD.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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