Site of action of grayanotoxins in mad honey in rats

Abstract

Grayanotoxins are known to occur in honey produced from the nectar of Rhododendrons of the family Ericaceae. Grayanotoxins extracted from honey sample obtained from a patient who experienced severe bradycardia and hypotension after ingesting two tablespoonfuls corresponded to Rhododendron ponticum tetrades. Anaesthetized albino rats were injected with honey extract intracerebroventricularly or intraperitoneally. The intracerebroventricular dose was equivalent to 50 mg honey and i.p. doses were equivalent to 50 mg, 1 mg kg-1 and 5 g kg-1 honey. Marked bradycardia and respiratory rate depression were observed in rats injected with extract equivalent to 1 and 5 g kg-1 honey i.p. and in rats injected with 50 mg i.c.v., but not in rats given 50 mg i.p. In bilaterally vagotomized animals, grayanotoxin-contaminated honey extract was not bradycardic. These results suggest that the sites of cardiac and respiratory actions are within the central nervous system, and that the bradycardic effect of grayanotoxin is mediated by vagal stimulation at the periphery.

The dose-dependent effect of grayanotoxin on the cardiovascular system

“…This finding is in agreement with the more severe cardiac findings in patients with a higher ingestion of honey in clinical series. Some experimental studies have reported that grayanotoxin also has a suppressive effect on respiratory functions (8,14). Although, in our study, respiratory frequency increased toward the end of the experiment in comparison to baseline values in animals administered high doses of GTX-III, this rise was not statistically significant.…”

“…Some cases proceed with mild symptoms, such as nausea, vomiting, dizziness, and low blood pressure, but cases of complete block and asystole have also been reported (10,12). GTX can affect the central nervous system, skeletomuscular system, respiratory system, heart, and peripheral nervous system (8,13). In an experimental study, Onat et al showed the effects of GTX on the respiratory system, central nervous system, and peripheral nervous system by inducing bradycardia and respiratory depression in rats.…”

“…All the observed responses of skeletal and heart muscles, nerves, and the central nervous system are related to the membrane effects (7). It has been suggested that sites of cardiac and respiratory activity of GTX are within the central nervous system and that bradycardiac effects of GTX are mediated by vagal stimulation at the periphery (8,9). There have been no studies showing the dose-dependent effect of GTX on the cardiovascular system.…”

Mad honey poisoning accompanied by hypotension and bradycardia

“…Ayrıca, GT II'de sinoatriyal noda spontan atımı baskılama özelliğine sahiptir. 10 GT' ler hücre membranlarındaki sodyum kanallarına bağlanarak etkilerini gösterir. Hücre membranlarındaki sodyum kanal geçirgenligini artı-rır, hücre membranında sodyum geçirgenliğinin artmasıyla repolarizasyon inhibe olur ve hücre membranı depolarizasyon süresi uzar.…”

Grayanotoxin (Mad Honey) - Ongoing Consumption After Poisoning

“…In the literature, high doses of Grayanotoxin have been reported in samples collected from patients that consumed two table spoons of mad honey and that were subsequently diagnosed with severe bradycardia and hypotension (4). This kind of honey, mostly produced in the Black Sea region of Turkey, is considered a healing honey and may not cause toxic effects in every consumer.…”