Is grayanotoxin directly responsible for mad honey poisoning-associated seizures

Aim: The aim of this study was to investigate the effects of grayanotoxin on epileptiform activity in rats. Materials and methods: Forty-two male Sprague Dawley rats were equally divided into 1 of 7 groups. Thirty minutes after induction of epileptiform activity induced by penicillin injection, 0.5, 1, 2, 4, or 8 μg of grayanotoxin-III was intracerebroventricularly administered. Epileptiform activity spike frequency and amplitude were converted into numerical data using software following the experiment. Results: Our results show that grayanotoxin reduces epileptiform spike frequency and amplitude in a dose-dependent manner. Five minutes postinjection, grayanotoxin significantly reduced epileptiform activity, especially at higher doses. This acute effect subsequently declined, but a dose-dependent decrease was observed through the end of the experiment. This suggests that the first observed effect of grayanotoxin on spikes probably consists of blocking voltage-gated sodium channel inactivation. Conclusion: Grayanotoxin’s suppression of epileptiform activity in this experimental study indicates that grayanotoxin is not directly responsible for mad honey poisoning-associated seizures observed in a clinical context.