Oleandrin is a cardiac glycoside found in the poisonous plant oleander (Nerium oleander L.). As a main phytochemical of oleander, oleandrin is associated with the toxicity of oleander sap, and has similar properties to digoxin. Oleandrin and other oleander chemicals are potentially toxic to the heart, liver, and kidneys. Although oleander has been used in traditional medicine and as a dietary supplement, there is no clinical evidence that oleander and its constituents, including oleandrin, are safe or effective for any therapeutic purpose. Oleandrin is not approved by regulatory agencies as a prescription drug.
Structure and reactivity The structure of oleandrin contains a central steroid nucleus with an unsaturated lactone ring structure on C17 and a dideoxy arabinose group on C3. In addition, the steroid ring has a substitute of an acetyloxy group on C16. The sugar forming the glycoside is L-oleandrose. Oleandrin resembles very much other glycosides like ouabain and digoxin but has less effect than digoxin. It is however, just like its derivate oleandrigenin, a more potent glycoside than ouabain.
Synthesis Oleandrin and its derivate oleandrigenin are formed in the N. oleander plant. The oleandrin itself can be won out of the leaves and other parts of the plant but can also be produced in the lab by using cell cultures. Here, the oleandrin synthesis (along with other metabolites) can be stimulated in untransformed plant cell cultures with supplementation of phytohormone. However, this is not enough to produce large quantities because of early cell death. Transgenic cultures of Agrobacteria are able to synthesize great quantities of oleandrin and other metabolites of the oleander plants, fit for pharmaceutical purposes.
Related substances Oleandrin is, apart from its pure form, also closely related to structural similar glycosides and alkaloids, which all have more or less the same characteristics as oleandrin:
Oleandrigenin is a deglycosylated metabolite of oleandrin. It has however a more mild effect. Conessine Neritaloside Odorside
Metabolism Although oleandrigenin is not formed in human plasma, it was found in the volunteers injected with oleandrin, suggesting that it is formed in other human tissues. Because of its lipophilic properties, oleandrin can be easily absorbed in the gastrointestinal tract after oral dosing. The clearance is slow. The plasma concentration obtains its maximum at twenty minutes after oral intake (half-life of about 2 hours, but half-life after IV administration is half an hour). It is excreted mostly in feces, but also in urine. Because the main route of excretion is through biliary excretion into the feces, it is mainly the liver that is exposed to oleandrin. As excretion in urine is only a smaller route, the kidneys are less exposed. There is also accumulation in the heart, which explains its potential for cardiac toxicity.
Mechanism of action Because of its properties as a cardiac glycoside, oleandrin interferes in some essential processes within the cell, the most important of these being the inhibition of the Na-K ATPase. This protein enables the cell to exchange the cations Na+ and K+ between the intercellular and extracellular spaces by which, for instance, electric signaling is made possible in nerve cells. Oleandrin binds to specific amino acids in the protein, causing it to lose its function. Apart from being a potent toxic compound, there are no results on oleandrin from human clinical research that support its use as a treatment for cancer or any disease.
Toxicity Due to its considerable toxicity, use of oleander or its constituents, such as oleandrin, is regarded as unsafe and potentially lethal. Use of oleander may cause contact dermatitis, headache, nausea, lethargy, and high blood levels of potassium, with symptoms appearing within a few hours of ingestion. In one fatality, the blood concentration of oleandrin and a related cardiac glycoside from the oleander plant was estimated at 20 ng/ml. In practice, there have been adult cases wherein 14–20 oleander leaves (of unknown oleandrin concentration) proved not to be fatal, but also a lethal case of a child that consumed only one leaf.
Symptoms Symptoms of oleandrin poisoning can cause both gastrointestinal and cardiac effects. The gastrointestinal effects can consist of nausea, abdominal pain, and vomiting, as well as higher salivation and diarrhea (which may contain blood). After these first symptoms, the heart may be affected by tachyarrhythmia, bradyarrhythmia, premature ventricular contractions, or atrioventricular blockage. Also, xanthopsia (yellow vision), a burning sensation of the mucous membranes of the eyes, and gastrointestinal tract and respiratory paralysis can occur. Reactions to poisonings from this plant can also affect the central nervous system. These symptoms can include drowsiness, tremors, or shaking of the muscles, seizures, collapse, and even coma that can lead to death. Oleander sap can cause skin irritations, severe eye inflammation and irritation, and allergy reactions characterized by dermatitis when administered topically.
Diagnosis Diagnosis of oleandrin poisoning is mainly based on description of the plant, how much of it was ingested, time since ingestion, and symptoms. Three methods are used for detecting oleandrin in the blood. Fluorescence polarization immunoassay is widely used. This test is slower and has a lower sensitivity than digoxin immunoassay (Digoxin III). A direct analytic technique like liquid chromatography-electrospray tandem mass spectrometry is used when there are medical or legal issues.
Treatment
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