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 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Nonprofit
- David and Elaine Potter Foundation
- Nonprofit
- Ian Potter Foundation
- University or hospital
- Cancer Institute NSW
- University or hospital
- University of Sydney
- Nonprofit
- PKD Australia
- Government
- Medical Research Council
- Government
- National Health and Medical Research Council
- University or hospital
- University of Sydney, Research Training Program Stipend
- Government
- National Health and Medical Research Council of Australia
- Grants
- National Health and Medical Research Council (1138533); National Health and Medical Research Council (1164128)
Based on 9 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2021-04-22 · PLoS One · vol. 16 · issue 4 · p. e0248400
- Publisher
- Public Library of Science
- Cited
- 16 citations · more than 89% of similar papers · 2.3× the field average
- References
- 76 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Genetic and Kidney Cyst Diseases · Biomedical Research and Pathophysiology · Birth, Development, and Health
- Keywords
- 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 authors
From AU
- Jennifer Q. J. ZhangThe University of Sydney; Westmead Hospital; Sydney Local Health District; Westmead Institute for Medical Research; Western Sydney Local Health District
- Sayanthooran SaravanabavanThe University of Sydney; Westmead Hospital; Sydney Local Health District; Westmead Institute for Medical Research; Western Sydney Local Health District
- Kai ChengThe University of Sydney; Westmead Hospital; Sydney Local Health District; Westmead Institute for Medical Research; Western Sydney Local Health District
- Aarya RaghubanshiThe University of Sydney; Westmead Hospital; Sydney Local Health District; Westmead Institute for Medical Research; Western Sydney Local Health District
- Ashley N. ChandraThe University of Sydney; Westmead Hospital; Sydney Local Health District; Westmead Institute for Medical Research; Western Sydney Local Health District
- Alexandra MuntThe University of Sydney; Westmead Hospital; Sydney Local Health District; Westmead Institute for Medical Research; Western Sydney Local Health District
Abstract
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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