M. Tariq et al., Diethyldithiocarbamate (DEDC) impairs neuronal recovery following sciatic nerve injury in rats, REST NEUROL, 17(2-3), 2000, pp. 135-141
Purpose: Diethyldithiocarbamate (DEDC) is a substituted dithiocarbamate tha
t is metabolically interconvertible with disulfiram (Antabuse). In recent y
ears DEDC has received considerable attention because of its clinical appli
cations and potential role in mediating both the toxic and therapeutic acti
ons of disulfiram which is frequently used for alcohol aversion therapy. DE
DC is known for its multiplicity of action that exerts both pro- and antiox
idant effects. In rodents DEDC has been shown to produce neuroprotective as
well as neurotoxic effects. The purpose of this study was to examine the e
ffect of DEDC on neurological recovery following sciatic nerve crush injury
(SNCI) in rats.
Methods: Adult female Wistar rats were subjected to SNCI with a haemostat u
nder deep anaesthesia. The animals were orally treated with DEDC at the dos
es of 250 mg/kg, 500 mg/kg and 750 mg/kg body weight 1 hr before SNCI and t
hen once daily for 60 days. The animals were observed for sciatic functiona
l index (walking deficit), electrophysiological and histological changes. V
itamin E level was measured to determine antioxidant status of sciatic nerv
e.
Results: Crush injury to the sciatic nerve resulted in a significant impair
ment of functional response which gradually recovered over a period of 22 d
ays. Treatment of animals with DEDC caused a significant delay in functiona
l recovery which was accompanied by poor histological and electrophysiologi
cal outcome. Prooxidant effect of DEDC is quite evident from a significant
decrease in vitamin E levels in both injured and uninjured sciatic nerves.
Conclusions: Our results demonstrate that exposure to DEDC adversely affect
s recovery from peripheral nerve injury. The delay may to some extent be at
tributed to DEDC induced oxidative stress.