Rhododendron

Source [1][2]

Rhododendrons are popular garden shrubs with bright flowers that bloom in spring.  Rhododendrons are found in Europe, North America, Japan, Napal, and Turkey. Both rhododendron ponticum, the common rhododendron, and rhododendron macrophyllum, the pacific rhododendron, contain grayanotoxins. Grayanotoxins are a neurotoxin that is found in all parts of the plant- stem, leaves, flower, pollen, and nectar. The main route of human exposure is from secondary products of this plant that get consumed such as honey and tea.

Chemical Composition[2]

There are three types of toxic grayanotoxins that exist: GTX-I, GTX-II, and GTX-III. GTX-I and GTX-III are the most potent. These structures do not undergo biotransformation within the system, but binds unchanged to the sodium channel unaltered.

Toxicokinetics [3]

Grayanotoxin poisoning typically occurs through the gastrointestinal tract with clinical signs only lasting ~1-2 days. They bind to sodium channels in the nerve, heart, and skeletal muscle causing those cells to constantly be depolarized.

Mechanism of Action [4]

Grayanotoxins bind to sodium channels when they are active and induces conformational changes in the channels leading to a prolonged depolarization.

Target organs [4]

Prolonged depolarization leads to overstimulation of the central nervous system (CNS), cardiovascular, and respiratory impairment. These organs are highly innervated so they are a greater risk of being affected by grayanotoxins.

Signs and symptoms of toxicity [4]

• Nausea, vomiting, dizziness, clouded vision, impaired consciousness, low blood pressure, hypotension are symptoms of grayanotoxin poisoning.
• Fainting and shock can occur in severe cases, even death has occurred although it is rare.

Genetic susceptibility or heritable traits [4]

There is no genetic susceptibility or heritable trait involved with grayanotoxin poisonings but people with pre-existing cardiovascular or respiratory issues are most at risk for serious life threatening side effects.

Historical or unique exposures [4]

The most common type of exposure in humans comes from eating grayanotoxin containing ‘mad honey’, a honey made from rhododendron pollen. Mad honey is deliberately produced in Nepal and Turkey as a recreational drug and for its perceived medicinal benefits and is legal to consume in the United States.

 

A historical use of mad honey was in 69 BC, King Mithridates used mad honey against an unknowing attacking army and when the rival soldiers became sick, Mithtidates army attacked.

Treatments [4]

There are no treatments for grayanotoxin poisoning, symptoms are typically treated with supportive therapy [5].

Diagnostics[5]

There are no biomarkers that indicate grayanotoxicity but diagnostics can be run using Liquid chromatography-mass spectrometry (LC-MS/MS) using blood, intestinal contents, urine, and feces to measure the toxins presence.

References:

1. Watkins JB. Chapter 26: Toxic Effects of Plants and Animals. Cassarett and Doull’s Toxicology: The Basic Science of Poisons, 8e.
2. Hodgson E. Toxins and Venoms: Progress in Molecular Biology and Translational Science. 2012; 112: 373-415.
3. Georghiou GP. The ABC and XYZ of Bee Culture. A.I. Root Company. 1980.
4. FDA. Bad Bug Book: Handbook of Foodborne Pathogenic Microorganisms and Natural Toxins, 2e. Available from: https://www.fda.gov/media/83271/download
5. Aygun A, Sahin A, Karaca Y, Turkmen S, et al. Grayanotoxin levels in blood, urine and honey and their association with clinical status in patients with mad honey intoxication. Turkish Journal of Emergency Medicine. 2018 Mar; 18(1): 29–33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009811/