Zinc has been proven to be
anticonvulsant in several studies which indicate that
diphenylthiocarbazone (
dithizone) and
diethyldithiocarbamate (DEDTC),
zinc chelating agents, enhance seizure activities. There is also evidence that
nitric oxide (NO) generators increase
zinc concentration in the brain. On the other hand, the increased level of NO in the nervous system and the consequently increased seizure threshold in cholestatic mice have been well studied. Thus, it could be hypothesized that one of the reasons for the increased seizure threshold in
cholestasis is partly the enhanced endogenous
zinc concentration, at least in part, due to the overproduction of NO. In this study, we examined the hypothesis that
zinc chelating agents might decrease seizure activity to its pre-cholestatic level in bile duct-ligated (BDL) mice. Mice were intra-peritoneally injected with
dithizone and
diethyldithiocarbamate (DEDTC) before the induction of seizure by
pentylenetetrazole (PTZ) and then the seizure activity was recorded. Dose response (
dithizone: 5, 30, 100 and 200mg/kg; DEDTC: 25, 50 and 100mg/kg) and time course (only for
dithizone: 15, 30, 60 and 120 min) studies were performed first. Then, the effects of
cholestasis, with and without
dithizone injection, on seizure activity were assessed. Proconvulsant effect of
dithizone and DEDTC was proved to be dose dependent although time interval between
dithizone and PTZ
injections did not play any significant role in the seizure activity.
Cholestasis decreased seizure activity and increased lag phase before seizure and both effects were decreased by
dithizone injection. It is elicited that
zinc may mediate the
cholestasis-induced decrement in seizure activity.