Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
Department of Biomedical Engineering, Indiana University-Purdue University, Indianapolis, IN, United States of America.
PLoS One. 2020 Mar 23;15(3):e0230379. doi: 10.1371/journal.pone.0230379. eCollection 2020.
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.
患有慢性肾病的个体氧化应激水平升高，骨骼骨折的风险显著增加。已知在骨骼中积累并损害机械性能的晚期糖基化终产物 (AGE) 在一定程度上是由氧化应激驱动的。本研究的目的是研究 N-乙酰半胱氨酸 (NAC) 在降低氧化应激和改善进行性 CKD 动物模型中各种骨参数方面的作用，特别是机械性能。雄性 Cy/+（CKD）大鼠和未受影响的同窝仔鼠未接受治疗（对照组）或从 30 到 35 周龄接受 NAC（80mg/kg，IP）治疗。终点测量包括血清生化指标、系统氧化应激评估、骨形态和机械性能以及骨中的 AGE 水平。CKD 大鼠具有预期的表型，包括肾功能低下、甲状旁腺激素升高、皮质骨多孔性增加和机械性能受损。NAC 治疗对氧化应激标志物有混合影响，显著降低 TBARS（衡量脂质过氧化的指标），而不影响 8-OHdG（衡量 DNA 氧化的指标）水平。骨中的 AGE 水平在 CKD 动物中升高，并随 NAC 降低，尽管这并未转化为骨机械性能的改善。总之，NAC 未能显著改善我们进行性 CKD 大鼠模型中的骨结构/几何形状/机械性能。
