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N-acetylcysteine (NAC), an anti-oxidant, does not improve bone mechanical properties in a rat model of progressive chronic kidney disease-mineral bone disorder

Individuals with chronic kidney disease have elevated levels of oxidative stress and are at a significantly higher risk of skeletal fracture. Advanced glycation end products (AGEs), which accumulate in bone and compromise mechanical properties, are known to be driven in part by oxidative stress. The...

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Autores principales: Allen, Matthew R., Wallace, Joseph, McNerney, Erin, Nyman, Jeffry, Avin, Keith, Chen, Neal, Moe, Sharon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089527/
https://www.ncbi.nlm.nih.gov/pubmed/32203558
http://dx.doi.org/10.1371/journal.pone.0230379
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author Allen, Matthew R.
Wallace, Joseph
McNerney, Erin
Nyman, Jeffry
Avin, Keith
Chen, Neal
Moe, Sharon
author_facet Allen, Matthew R.
Wallace, Joseph
McNerney, Erin
Nyman, Jeffry
Avin, Keith
Chen, Neal
Moe, Sharon
author_sort Allen, Matthew R.
collection PubMed
description Individuals with chronic kidney disease have elevated levels of oxidative stress and are at a significantly higher risk of skeletal fracture. Advanced glycation end products (AGEs), which accumulate in bone and compromise mechanical properties, are known to be driven in part by oxidative stress. The goal of this study was to study effects of N-acetylcysteine (NAC) on reducing oxidative stress and improving various bone parameters, most specifically mechanical properties, in an animal model of progressive CKD. Male Cy/+ (CKD) rats and unaffected littermates were untreated (controls) or treated with NAC (80 mg/kg, IP) from 30 to 35 weeks of age. Endpoint measures included serum biochemistries, assessments of systemic oxidative stress, bone morphology, and mechanical properties, and AGE levels in the bone. CKD rats had the expected phenotype that included low kidney function, elevated parathyroid hormone, higher cortical porosity, and compromised mechanical properties. NAC treatment had mixed effects on oxidative stress markers, significantly reducing TBARS (a measure of lipid peroxidation) while not affecting 8-OHdG (a marker of DNA oxidation) levels. AGE levels in the bone were elevated in CKD animals and were reduced with NAC although this did not translate to a benefit in bone mechanical properties. In conclusion, NAC failed to significantly improve bone architecture/geometry/mechanical properties in our rat model of progressive CKD.
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spelling pubmed-70895272020-04-01 N-acetylcysteine (NAC), an anti-oxidant, does not improve bone mechanical properties in a rat model of progressive chronic kidney disease-mineral bone disorder Allen, Matthew R. Wallace, Joseph McNerney, Erin Nyman, Jeffry Avin, Keith Chen, Neal Moe, Sharon PLoS One Research Article Individuals with chronic kidney disease have elevated levels of oxidative stress and are at a significantly higher risk of skeletal fracture. Advanced glycation end products (AGEs), which accumulate in bone and compromise mechanical properties, are known to be driven in part by oxidative stress. The goal of this study was to study effects of N-acetylcysteine (NAC) on reducing oxidative stress and improving various bone parameters, most specifically mechanical properties, in an animal model of progressive CKD. Male Cy/+ (CKD) rats and unaffected littermates were untreated (controls) or treated with NAC (80 mg/kg, IP) from 30 to 35 weeks of age. Endpoint measures included serum biochemistries, assessments of systemic oxidative stress, bone morphology, and mechanical properties, and AGE levels in the bone. CKD rats had the expected phenotype that included low kidney function, elevated parathyroid hormone, higher cortical porosity, and compromised mechanical properties. NAC treatment had mixed effects on oxidative stress markers, significantly reducing TBARS (a measure of lipid peroxidation) while not affecting 8-OHdG (a marker of DNA oxidation) levels. AGE levels in the bone were elevated in CKD animals and were reduced with NAC although this did not translate to a benefit in bone mechanical properties. In conclusion, NAC failed to significantly improve bone architecture/geometry/mechanical properties in our rat model of progressive CKD. Public Library of Science 2020-03-23 /pmc/articles/PMC7089527/ /pubmed/32203558 http://dx.doi.org/10.1371/journal.pone.0230379 Text en © 2020 Allen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Allen, Matthew R.
Wallace, Joseph
McNerney, Erin
Nyman, Jeffry
Avin, Keith
Chen, Neal
Moe, Sharon
N-acetylcysteine (NAC), an anti-oxidant, does not improve bone mechanical properties in a rat model of progressive chronic kidney disease-mineral bone disorder
title N-acetylcysteine (NAC), an anti-oxidant, does not improve bone mechanical properties in a rat model of progressive chronic kidney disease-mineral bone disorder
title_full N-acetylcysteine (NAC), an anti-oxidant, does not improve bone mechanical properties in a rat model of progressive chronic kidney disease-mineral bone disorder
title_fullStr N-acetylcysteine (NAC), an anti-oxidant, does not improve bone mechanical properties in a rat model of progressive chronic kidney disease-mineral bone disorder
title_full_unstemmed N-acetylcysteine (NAC), an anti-oxidant, does not improve bone mechanical properties in a rat model of progressive chronic kidney disease-mineral bone disorder
title_short N-acetylcysteine (NAC), an anti-oxidant, does not improve bone mechanical properties in a rat model of progressive chronic kidney disease-mineral bone disorder
title_sort n-acetylcysteine (nac), an anti-oxidant, does not improve bone mechanical properties in a rat model of progressive chronic kidney disease-mineral bone disorder
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089527/
https://www.ncbi.nlm.nih.gov/pubmed/32203558
http://dx.doi.org/10.1371/journal.pone.0230379
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