dithizone and Seizures

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.

Topics: Animals; Bile Ducts; Chelating Agents; Cholestasis; Disease Models, Animal; Dithizone; Ditiocarb; Dose-Response Relationship, Drug; Male; Mice; Pentylenetetrazole; Seizures; Severity of Illness Index; Statistics, Nonparametric; Time Factors

Male Fischer-344 rats were injected i.p. with diethyldithiocarbamate or dithizone 15 min after kainic acid (KA), s.c. Diethyldithiocarbamate and dithizone reduced both the number of wet dog shakes and the latency to onset of seizures induced by KA. Moreover, they increased the severity of seizures. These compounds may be useful tools for investigating the role of zinc in central nervous system excitatory transmission and/or convulsive phenomena.

Topics: Animals; Azo Compounds; Chelating Agents; Dithizone; Ditiocarb; Kainic Acid; Male; Rats; Rats, Inbred F344; Reaction Time; Seizures; Zinc