Am J Physiol Renal Physiol. 2023 Jul 13. doi: 10.1152/ajprenal.00083.2023. Online ahead of print.
ABSTRACT
The objective of this study was to determine if treatment with N-acetylcysteine (NAC) could reduce access-related limb dysfunction in mice. Male and female C57BL6J mice were fed an adenine supplemented diet to induce chronic kidney disease prior to surgical creation of an arteriovenous fistula (AVF) in the iliac vascular bundle. AVF creation significantly increased peak aortic and infrarenal vena cava blood flow velocities, but NAC treatment had no significant impact indicating that fistula maturation was not impacted by NAC treatment. Hindlimb muscle and paw perfusion recovery and muscle capillary density in the AVF limb were unaffected by NAC treatment. However, NAC treatment significantly increased the mass of the tibialis anterior (P=0.0120) and soleus (P=0.0452) muscles post-AVF. There was a significant main effect of NAC treatment on hindlimb grip strength at post-operative day (POD) 12 (P=0.0003), driven by significantly higher grip strength in both male (P=0.0273) and female (P=0.0031) mice treated with NAC. There was also a significant main effect of NAC treatment on walking speed at POD12 (P=0.0447), and post-hoc testing revealed improvement in NAC male mice (P=0.0091). The area of post-synaptic acetylcholine receptors (P=0.0263) and motor endplates (P=0.0240) were also increased by NAC treatment. Interestingly, hindlimb skeletal muscle mitochondrial oxidative phosphorylation was trending higher in NAC female mice but was not statistically significant (P=0.0973). Muscle glutathione levels and redox status were not significantly impacted by NAC treatment in either sex. In summary, NAC treatment attenuated some aspects of neuromotor pathology in mice with chronic kidney disease following AVF creation.
PMID:37439200 | DOI:10.1152/ajprenal.00083.2023
