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


RESULTS
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.


CONCLUSIONS
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.
West
C A
CA
Blond McIndoe Research Laboratories, University of Manchester, Manchester, UK.
Hart
A M
AM
Terenghi
G
G
Wiberg
M
M
D000111:Acetylcysteine / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000473:pathology*; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries* / Q000473:pathology*; D014947:Wounds and Injuries / Q000473:pathology
D000111:Acetylcysteine