Oleandrin
Encyclopedia
Oleandrin is a toxic cardiac glycoside
found in oleander
(Nerium oleander L.). Along with neandrin it is primarily responsible for the toxicity of the sap of oleander. Oleandrin has been used for many years in China and Russia for its properties as a cardiac glycoside, for both suicidal and therapeutic purposes as in treatment of cardiac insufficiency.
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 a acetyloxy group on C16.
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.
are able to synthesize great quantities of oleandrin and other metabolites of the oleander plants, fit for pharmaceutical purposes.
, 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, electronic signaling is made possible in nerve cells. Oleandrin binds to specific amino acids in the protein, causing it to lose its function. After depolarization of the cell in which Na+ flows into the cell, the Na+ cannot be transported back into the extracellular membrane, causing a the sodium gradient to disappear. This gradient is the driving force for other transport proteins, such as the sodium-calcium exchanger
, which plays an important role in cardiomyocytes.
To make muscle contraction possible, a calcium influx from the extracellular fluid into the cell is crucial. After the muscle contraction, the calcium is normally pumped out of the cell and exchanged for sodium. When the sodium gradient is depleted, calcium cannot be pumped back and, as a consequence, accumulates in the cardiomyocyte.
As a result of the high calcium concentration, actin and myosin filaments will bind stronger, unable to relax properly to make a new contraction possible. This may result in cardiac arrhythmias, in the worst case decreasing cardiac output and causing a shortage in oxygen supply in vital tissues.
Apart from being a potent toxic compound, it can also be used in therapeutic ways. Both oleandrin and oleandrigenin, as well as their relatives, are able to inhibit proliferation of tumor cells and stimulate their apoptosis
as a result of the high concentration of intracellular calcium. In addition, it inhibits excretion of fibroblast growth factor 2 through membrane interaction and through inhibition of the Na,K-ATPase pump.
age. 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.
poisoning, and being in a region with N. oleander
suggest poisoning with the plant.
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 medicolegal issues.
Previously forced vomiting or performing gastric lavage
was part of the treatment of poisoning, but is no longer recommended.
There is a lack of evidence that weighs efficacy versus harm.
Activated charcoal is still used, since it binds toxins in the gastrointestinal tract to reduce absorption. It is uncertain whether repeated administration of activated charcoal is effective, in theory interrupting enterohepatic cycling
. This treatment is used for digoxin poisoning, another cardiac glycoside.
Supportive care like monitoring vitals and electrolyte and fluid balance is important. Patients may present hypovolemic due to vomiting and diarrhea, but severely elevated potassium can also occur.
Electrolyte balance is vital, since patients with low cardiac glycoside levels can still die after adequate digoxin Fab antibody treatment if they have disturbed electrolyte levels.
Treatment of bradyarrhythmias is by many done with intravenous isoprenaline and/or atropine.
In moderate cases, prolonging of the PR interval and progression to AV dissociation, cardiac pacing is used.
The effectiveness of all these interventions is unknown and are associated with side-effects. Therefore, consultation with a cardiologist is recommended when managing significant N. Oleander induced arrhythmias. The use of anti-digoxin Fab IV has proven successful in cases of oleandrin poisoning
These antibodies have shown to bind in vitro with oleandrin and thus reduce the active concentration in the blood
A dose of 400 mg is used in digoxin poisoning, but a dose of 800 mg is recommended for oleandrin poisoning due to the lower binding affinity of the antibody to oleandrin. Patients receiving an adequate dose of anti-digoxin Fab show a good response, resolving serious arrhythmias in two hours in fifty percent of the cases. Treated patients showed a rapid increase in heart rate and a significant decline in serum potassium levels. The reason anti-digoxin Fab is sparingly used in developing countries is its high cost, even though it is such an effective treatment.
, non-small cell lung cancer, leukemia
, pancreas
, melanoma
and prostate
. It may work as a cytotoxic agent, generating reactive oxygen species
or inducing apoptosis
, but has also shown to be synergistic with current chemotherapy. This may be due to its potential to inhibit P-glycoprotein
. This transporter is responsible for phenotypes of cancer resistant to chemotherapeutic agents.
Although this sounds promising, in general, concentrations needed for therapeutic effect are not achievable in patient plasma. Apart from being a chemosensitizer
, oleandrin has shown to be a potent radiosensitizer
. Oleandrin increases caspase 3
activity in radiodamaged tumor cells and, therefore, increases radiation-induced apoptosis. It is unclear as to whether normal cells suffer the same degree of radiosensitization; however, if they do, oleandrin might not be suitable for combined treatment with radiation therapy.
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 2,3±0,5h, but half-life after IV administration is 0,4±0,1h).
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 cardiac tissue, which explains its potential for cardiac toxicity. In mouse studies, it also appeared that oleandrin rapidly accumulates in brain tissue, as it can pass through the blood-brain barrier
. The data suggest that other components within oleander extract may enhance transport of oleandrin across the blood-brain barrier.
Symptoms present in poisoned animals include bloody diarrhea and colic
, the latter especially in horses
. Because the leave itself is quite bitter, only starving animals will be likely to eat the plant. The lethal dosage for animals is estimated to be about 0.5 mg/kg.
Cardiac glycoside
Cardiac glycosides are drugs used in the treatment of congestive heart failure and cardiac arrhythmia. These glycosides are found as secondary metabolites in several plants, but also in some animals, such as the milkweed butterflies. -Function:...
found in oleander
Oleander
Nerium oleander is an evergreen shrub or small tree in the dogbane family Apocynaceae, toxic in all its parts. It is the only species currently classified in the genus Nerium. It is most commonly known as oleander, from its superficial resemblance to the unrelated olive Olea, but has many other...
(Nerium oleander L.). Along with neandrin it is primarily responsible for the toxicity of the sap of oleander. Oleandrin has been used for many years in China and Russia for its properties as a cardiac glycoside, for both suicidal and therapeutic purposes as in treatment of cardiac insufficiency.
Structure and reactivity
The structure of oleandrin contains a central steroidSteroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
nucleus with an unsaturated lactone
Lactone
In chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule...
ring structure on C17 and a dideoxy arabinose group on C3. In addition, the steroid ring has a substitute of a acetyloxy group on C16.
Oleandrin resembles very much other glycosides like ouabain
Ouabain
Ouabain which is also named g-strophanthin, is a poisonous cardiac glycoside.-Sources:Ouabain is found in the ripe seeds of African plants Strophanthus gratus and the bark of Acokanthera ouabaio.-Function:...
and digoxin
Digoxin
Digoxin INN , also known as digitalis, is a purified cardiac glycoside and extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin...
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 AgrobacteriaAgrobacterium
Agrobacterium is a genus of Gram-negative bacteria established by H. J. Conn that uses horizontal gene transfer to cause tumors in plants. Agrobacterium tumefaciens is the most commonly studied species in this genus...
are able to synthesize great quantities of oleandrin and other metabolites of the oleander plants, fit for pharmaceutical purposes.
Available forms
Oleandrin is, apart from its pure form, also closely related to structural similar glycosides, 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.
- Neandrin
- Neritaloside
- Odorside
Mechanism of action
Because of its properties as a cardiac glycosideCardiac glycoside
Cardiac glycosides are drugs used in the treatment of congestive heart failure and cardiac arrhythmia. These glycosides are found as secondary metabolites in several plants, but also in some animals, such as the milkweed butterflies. -Function:...
, 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, electronic signaling is made possible in nerve cells. Oleandrin binds to specific amino acids in the protein, causing it to lose its function. After depolarization of the cell in which Na+ flows into the cell, the Na+ cannot be transported back into the extracellular membrane, causing a the sodium gradient to disappear. This gradient is the driving force for other transport proteins, such as the sodium-calcium exchanger
Sodium-calcium exchanger
The sodium-calcium exchanger is an antiporter membrane protein that removes calcium from cells. It uses the energy that is stored in the electrochemical gradient of sodium by allowing Na+ to flow down its gradient across the plasma membrane in exchange for the countertransport of calcium ions...
, which plays an important role in cardiomyocytes.
To make muscle contraction possible, a calcium influx from the extracellular fluid into the cell is crucial. After the muscle contraction, the calcium is normally pumped out of the cell and exchanged for sodium. When the sodium gradient is depleted, calcium cannot be pumped back and, as a consequence, accumulates in the cardiomyocyte.
As a result of the high calcium concentration, actin and myosin filaments will bind stronger, unable to relax properly to make a new contraction possible. This may result in cardiac arrhythmias, in the worst case decreasing cardiac output and causing a shortage in oxygen supply in vital tissues.
Apart from being a potent toxic compound, it can also be used in therapeutic ways. Both oleandrin and oleandrigenin, as well as their relatives, are able to inhibit proliferation of tumor cells and stimulate their apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
as a result of the high concentration of intracellular calcium. In addition, it inhibits excretion of fibroblast growth factor 2 through membrane interaction and through inhibition of the Na,K-ATPase pump.
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 blockAtrioventricular block
An atrioventricular block involves the impairment of the conduction between the atria and ventricles of the heart.The causes of pathological AV block are varied and include ischaemia, infarction, fibrosis or drugs. Certain AV blocks can also be found as normal variants, such as in athletes or...
age. Also, xanthopsia
Xanthopsia
Xanthopsia refers to the predominance of yellow in vision due to a yellowing of the optic media of the eye. The most common cause is digoxin toxicity and the development of cataracts which can cause a yellow filtering effect....
(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
Dermatitis
-Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called...
when administered topically.
Diagnosis
Diagnosis of oleandrin poisoning is mainly based on a detailed history. Whether or not a plant is ingested, description of the plant, or the plant itself, how much of it was ingested, time between ingestion and symptoms are all relevant questions. These can be asked only when the patient is not unconscious, which may happen due to cardiac symptoms, or when a third person is present. Supportive treatment should always be given to those with severe cardiac arrhythmias. History of poisoning (of a plant), ECG abnormalities that fit digoxinDigoxin
Digoxin INN , also known as digitalis, is a purified cardiac glycoside and extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin...
poisoning, and being in a region with N. oleander
Oleander
Nerium oleander is an evergreen shrub or small tree in the dogbane family Apocynaceae, toxic in all its parts. It is the only species currently classified in the genus Nerium. It is most commonly known as oleander, from its superficial resemblance to the unrelated olive Olea, but has many other...
suggest poisoning with the plant.
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 medicolegal issues.
Treatment
Onset of symptoms may vary with the way of intake. Teas made of leaves or root of N. oleander give rise to a more acute onset, while eating raw leaves causes a slower onset of symptoms. Management of oleandrin poisoning is done in the following steps:- ResuscitateCardiopulmonary resuscitationCardiopulmonary resuscitation is an emergency procedure which is performed in an effort to manually preserve intact brain function until further measures are taken to restore spontaneous blood circulation and breathing in a person in cardiac arrest. It is indicated in those who are unresponsive...
the patient as necessary - Take pulse, blood pressure, and oxygen saturationOxygen saturationOxygen saturation or dissolved oxygen is a relative measure of the amount of oxygen that is dissolved or carried in a given medium. It can be measured with a dissolved oxygen probe such as an oxygen sensor or an optode in liquid media, usually water.It has particular significance in medicine and...
. Place on a cardiac monitor and take a 12-lead ECG. Insert IV cannula and give fluids IV - Treat marked hypotensionHypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
(systolic <70 mmHg) or bradycardiaBradycardiaBradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
(<40 bpm) with bolus dose of atropineAtropineAtropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...
(2–3 mg). Otherwise give small bolus of atropine (0.3-0.6 mg) or and infusion (0.6 mg/h) to keep heart rate around 70-80 bpm - Consider the administration of a single dose of activated charcoal to bind any oleandrin left in the gastrointestinal tract.
- Measure serum electrolyteElectrolyteIn chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
s and magnesium. Treat hypokalemiaHypokalemiaHypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
and hypomagnesemiaHypomagnesemiaHypomagnesemia is an electrolyte disturbance in which there is an abnormally low level of magnesium in the blood. Usually a serum level less than 0.7 mmol/L is used as reference. The prefix hypo- means low . The middle 'magnes' refers to magnesium...
until both concentrations are back in high-normal range - AV node and/or severe sinus node block, ventricular tachycardiaVentricular tachycardiaVentricular tachycardia is a tachycardia, or fast heart rhythm, that originates in one of the ventricles of the heart...
, and serum potassium >5.5 are indications for anti-digoxin FabDigoxin Immune FabDigoxin Immune Fab is the generic name for an antidote for overdose of digitalis. It is made from immunoglobulin fragments from sheep who have already been immunized with a digoxin derivative, digoxindicarboxymethoxylamine...
, if available. The best regimen is currently unclear. Consider giving 400 mg over 20 minutes followed by 400–800 mg over 4–8 hours by infusion. - In the absence of anti-digoxin Fab:
- Give insulin/dextrose for potassium >5,5. Do not give calcium.
- Consider treating severe bradycardia due to AV block with temporary pacing
- Treat ventricular fibrillationVentricular fibrillationVentricular fibrillation is a condition in which there is uncoordinated contraction of the cardiac muscle of the ventricles in the heart, making them quiver rather than contract properly. Ventricular fibrillation is a medical emergency and most commonly identified arrythmia in cardiac arrest...
with low-energy direct current cardioversion.
Previously forced vomiting or performing gastric lavage
Gastric lavage
Gastric lavage, also commonly called stomach pumping or Gastric irrigation, is the process of cleaning out the contents of the stomach. It has been used for over 200 years as a means of eliminating poisons from the stomach. Such devices are normally used on a person who has ingested a poison or...
was part of the treatment of poisoning, but is no longer recommended.
There is a lack of evidence that weighs efficacy versus harm.
Activated charcoal is still used, since it binds toxins in the gastrointestinal tract to reduce absorption. It is uncertain whether repeated administration of activated charcoal is effective, in theory interrupting enterohepatic cycling
Enterohepatic circulation
Enterohepatic circulation refers to the circulation of biliary acids from the liver, where they are produced and secreted in the bile, to the small intestine, where it aids in digestion of fats and other substances, back to the liver....
. This treatment is used for digoxin poisoning, another cardiac glycoside.
Supportive care like monitoring vitals and electrolyte and fluid balance is important. Patients may present hypovolemic due to vomiting and diarrhea, but severely elevated potassium can also occur.
Electrolyte balance is vital, since patients with low cardiac glycoside levels can still die after adequate digoxin Fab antibody treatment if they have disturbed electrolyte levels.
Treatment of bradyarrhythmias is by many done with intravenous isoprenaline and/or atropine.
In moderate cases, prolonging of the PR interval and progression to AV dissociation, cardiac pacing is used.
The effectiveness of all these interventions is unknown and are associated with side-effects. Therefore, consultation with a cardiologist is recommended when managing significant N. Oleander induced arrhythmias. The use of anti-digoxin Fab IV has proven successful in cases of oleandrin poisoning
These antibodies have shown to bind in vitro with oleandrin and thus reduce the active concentration in the blood
A dose of 400 mg is used in digoxin poisoning, but a dose of 800 mg is recommended for oleandrin poisoning due to the lower binding affinity of the antibody to oleandrin. Patients receiving an adequate dose of anti-digoxin Fab show a good response, resolving serious arrhythmias in two hours in fifty percent of the cases. Treated patients showed a rapid increase in heart rate and a significant decline in serum potassium levels. The reason anti-digoxin Fab is sparingly used in developing countries is its high cost, even though it is such an effective treatment.
Anti-Cancer Therapy
Oleandrin is a promising agent for anti-cancer treatment. Studies show potential in vitro effect for cancers of the colonColon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
, non-small cell lung cancer, leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
, pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
, melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
and prostate
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
. It may work as a cytotoxic agent, generating reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
or inducing apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, but has also shown to be synergistic with current chemotherapy. This may be due to its potential to inhibit P-glycoprotein
P-glycoprotein
P-glycoprotein 1 also known as multidrug resistance protein 1 or ATP-binding cassette sub-family B member 1 or cluster of differentiation 243 is a glycoprotein that in humans is encoded by the ABCB1 gene...
. This transporter is responsible for phenotypes of cancer resistant to chemotherapeutic agents.
Although this sounds promising, in general, concentrations needed for therapeutic effect are not achievable in patient plasma. Apart from being a chemosensitizer
Chemosensitizer
A chemosensitizer is a drug that makes tumor cells more sensitive to the effects of chemotherapy.- External links :* entry in the public domain NCI Dictionary of Cancer Terms...
, oleandrin has shown to be a potent radiosensitizer
Radiosensitizer
A radiosensitizer is a drug that makes tumor cells more sensitive to radiation therapy.One of the major limitations of radiotherapy is that the cells of solid tumors become deficient in oxygen. Solid tumors can outgrow their blood supply, causing a low-oxygen state known as hypoxia...
. Oleandrin increases caspase 3
Caspase 3
Caspase 3 is a caspase protein that interacts with caspase 8 and caspase 9. It is encoded by the CASP3 gene. CASP3 orthologs have been identified in numerous mammals for which complete genome data are available...
activity in radiodamaged tumor cells and, therefore, increases radiation-induced apoptosis. It is unclear as to whether normal cells suffer the same degree of radiosensitization; however, if they do, oleandrin might not be suitable for combined treatment with radiation therapy.
Metabolism
In mice, oleandrin is metabolized into oleandrigenin. Although oleandrigenin it 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 2,3±0,5h, but half-life after IV administration is 0,4±0,1h).
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 cardiac tissue, which explains its potential for cardiac toxicity. In mouse studies, it also appeared that oleandrin rapidly accumulates in brain tissue, as it can pass through the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
. The data suggest that other components within oleander extract may enhance transport of oleandrin across the blood-brain barrier.
Toxicity
Oleandrin has been reported to be lethal, but exact dosages are not fully documented. The fatal blood concentration of oleandrin has been estimated for humans to be approximately 20 ng/ml in decreased blood by extrapolation of intoxication symptoms. 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.Effects on animals
Oleandrin poisoning by eating oleander leaves can be lethal at low dosages. Cases of sheep lethality have been reported to only one leaf of Oleander.Symptoms present in poisoned animals include bloody diarrhea and colic
Colic
Colic is a form of pain which starts and stops abruptly. Types include:*Baby colic, a condition, usually in infants, characterized by incessant crying*Renal colic, a pain in the flank, characteristic of kidney stones...
, the latter especially in horses
Horse colic
Colic in horses is defined as abdominal pain, but it is a clinical sign rather than a diagnosis. The term colic can encompass all forms of gastrointestinal conditions which cause pain as well as other causes of abdominal pain not involving the gastrointestinal tract. The most common forms of colic...
. Because the leave itself is quite bitter, only starving animals will be likely to eat the plant. The lethal dosage for animals is estimated to be about 0.5 mg/kg.