The dose-dependent cardiovascular effects of intravenous grayanotoxin-III in rats

Abstract

Objective: The mad honey poisonings are commonly seen in our country. The source of the toxin in mad honey is plants of Rhododendron species. Grayanotoxin-III type toxin is commonly found in these plants. Clinical effects of this toxin are bradycardia, atrioventricular block, asystole, hypotension and symptoms such as salivation. In this study; different doses of grayanotoxin-III were intravenously administered to rats (i.v) and the effect of grayanotoxin on cardiovascular system was evaluated. Methods: This study was performed on 42 Wistar albino rats and the animals were divided into six groups. Control, Group 1 (5 mu g/kg), Group 2 (10 mu g/kg), Group 3 (20 mu g/kg), Group 4 (50 mu g/kg) and Group 5 (100 mu g/kg) groups were formed. Baseline values for electrocardiography (ECG), arterial blood pressure and respiratory rate were obtained and recorded for 60 minutes after administration of i.v. grayanotoxin-III. Results: Group1 (5 mu g/kg) was not significantly changed in all time periods. In 10 and 20 mu g/kg groups, respiratory rates, peak heart rates decreased significantly and drop in arterial blood pressures was observed after 2nd and 5th minutes. While 25 minutes after administration of i.v. grayanotoxin-III all parameters returned to baseline values again. In 50 and 100 mu g/kg grayanotoxin-III groups all parameters fell sharply from 2 minutes on, and rats died within 5-10 minutes. Conclusion: In conclusion, it was found that the lethal dose of grayanotoxin-III for rats is 50 mu g/kg. In addition the death was developed due to cardiac arrest. In case of the lower level of 5 mu g/kg grayanotoxin-III, any toxic effect was not seen. The effects of toxin apparently lasted nearly 25 minutes.