Analysis of the dose-response of N-acetylcysteine in the prevention of sensory neuronal loss after peripheral nerve injury

• Published in: Acta neurochirurgica. Supplement Vol. 100; p. 29
• Main Authors: West, C A, Hart, A M, Terenghi, G, Wiberg, M
• Format: Journal Article
• Language: English
• Published: Austria 2007
• Subjects: Acetylcysteine - administration & dosage; Acetylcysteine - pharmacology; Animals; Cell Count; Dose-Response Relationship, Drug; Ganglia, Spinal - drug effects; Ganglia, Spinal - pathology; Neurons, Afferent - drug effects; Neurons, Afferent - pathology; Rats; Sciatic Nerve - drug effects; Sciatic Nerve - injuries; Sciatic Nerve - pathology; Wounds and Injuries - pathology
• ISSN: 0065-1419
• DOI: 10.1007/978-3-211-72958-8_6

N-Acetylcysteine (NAC) is a safe pharmaceutical agent known to protect cells from oxidative damage. Following peripheral nerve transection, NAC has been found to eliminate sensory neuronal loss. This study examines the dose-response relationship of NAC in preventing neuronal death.
The rat sciatic nerve transection model was used, and stereological quantification of sensory neuron survival carried out at two weeks post-axotomy. NAC was administered systemically as an intraperitoneal injection to five groups of rats at a range of doses (1-300 mg/kg/day). Significant neuronal loss was observed in the 1 mg/kg/day dosage group (18.5% loss, p = 0.067 vs. sham treatment). A degree of neuroprotection occurred with 10 mg/kg/day (9.1% loss, p < 0.005 vs. control), whilst there was no significant loss with either 150 or 300 mg/kg/day.
The prevention of sensory neuronal loss with NAC is dose dependent and effective over a wide therapeutic range. This analysis confirms the efficacy of systemic administration and provides a dose framework with which NAC has clinical potential to improve outcome after peripheral nerve trauma.