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 MR, Wallace J, McNerney E, Nyman J, Avin K, Chen N, Moe S
PLoS One. 2020 15 (3): e0230379

PMID: 32203558 · PMCID: PMC7089527 · DOI:10.1371/journal.pone.0230379

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.

MeSH Terms (19)

Acetylcysteine Animals Antioxidants Caseins Chronic Kidney Disease-Mineral and Bone Disorder Disease Models, Animal Disease Progression Glycation End Products, Advanced Humans Kidney Lipid Peroxidation Male Mutation Nuclear Proteins Oxidative Stress Parathyroid Hormone Rats Tibia X-Ray Microtomography

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