Taxine

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Chemical structure of taxine A
Chemical structure of taxine B

Taxine is a toxic alkaloid compound present in the Yew tree, Taxus baccata.[1] It is composed of more than seven alkaloids, the main constituents being taxine A and taxine B;[2] the other components are their derivatives, such as 2-deacetyltaxine A, isotaxine B and 1-deoxytaxine B.[3]

This substance is characterized by high melting and boiling point. Taxine is soluble in chloroform and alcohol, and insoluble in water or oil. [4]

Properties of Taxine A
Molecular Formula C35H47NO10
Molecular weight 641.758 g/mol
Molar volume 499.9 ± 5.0 cm3
Density 1.3 ± 0.1 g/cm33
Boiling Point 747.1 ± 60.0 °C at 1 atm
Enthalpy of Vaporization 114.3 ± 3.0 kJ/mol
Index of Refraction 1.587
Rotatable Bond Count 10
Properties of Taxine B
Molecular Formula C33H45NO8
Molecular weight 583.7123 g/mol
Molar volume 466.4 ± 5.0 cm3
Density 1.3 ± 0.1 g/cm3
Boiling Point 676.9 ± 55.0 °C at 1 atm
Enthalpy of Vaporization 104.4 ± 3.0 kJ/mol
Index of Refraction 1.588
Rotatable Bond Count 8

Provenance[edit]

Taxus baccata's tree and its aril

Taxine can be found in Taxus species: Taxus cuspidata, T. baccata (English yew), Taxus x media, Taxus canadensis, Taxus floridana and Taxus brevifolia (Pacific or western yew). All of these species contain taxine in every part of the plant except in the aril, the fleshy covering of the seeds (berries), each species contains a different amount of taxine concentration, which leads to varying toxicities within the genus. This is the case of the Taxus brevifolia or Pacific yew and the Taxus baccata (English yew); T. baccata contains high taxine concentration, which leads to a high toxicity, whereas T. brevifolia has a low toxicity. There are seasonal changes in the concentrations of taxine in yew plants, with the highest concentrations during the winter, and the lowest in the summer.[5] Taxus species are one of the few trees that when they die, the poison is not destroyed, in other words, the effect of the Taxine continues functioning independently of the life of the yew in which it is contained.[6]

These species have distinctive leaves, which are needle like, small, spirally arranged but twisted so they are two-ranked, linear-lanceolate, they are also characterized by their ability to regenerate from stumps and roots.[7] They are found all over Europe and live in conditions similar to the oceanic specia and better in mixed forests (coniferous), on limestone substrates, and occupy rock cliffs and slopes, they are sensitive to low temperatures, the reason why they cannot be found in Northern Scandinavia. [8]

Toxicity in humans[edit]

Taxus baccata's seeds
Taxus baccata's leaves

Taxine poisoning can occur when parts of the yew tree are eaten. Taxine is found in all parts of the tree, except in the aril, that is, the fleshy red covering of the seeds. However, the seeds themselves are the most toxic part of the yew tree due to the quantity of taxine they contain.

Taxine remains in the plant all year, with maximal concentrations appearing during the winter. Dried yew plant material retains its toxicity for several months, so fallen leaves are also toxic, the lethal dose of leaves is relatively small: just 50g-100g of leaves can be enough to kill a human because taxine is a very powerful cardiotoxin.[9]

Although poisoning usually occurs when any part of the yew tree is eaten, in at least one case the victim inhaled sawdust from the yew tree. Having been inhaled through the mouth, this material entered the digestive tract and caused the symptoms of poisoning.[10]

Clinical signs[edit]

Taxine is rapidly absorbed by the body, so in some cases, the person poisoned may die before any other symptoms are manifested.

In other cases, patients present symptoms and death occurs several hours or days after ingestion. Common effects are:

3,5-Dimethoxyphenol molecule, used in the taxine poisoning diagnosis

Diagnosis[edit]

The diagnosis of yew poisoning is very important if the patient is not already aware of having ingested parts of the yew tree, the method of diagnosis is the determination of 3,5-dimethoxyphenol, a product of the hydrolysis of the glycosidic bond in taxine, in the blood, the gastric contents, the urine and the tissues of the patient. This analysis can be done by gas or liquid chromatography and also by mass spectroscopy.

Treatment[edit]

There are no specific antidotes for taxine, so patients can only receive treatment for their symptoms.

The first step of treatment is a rapid stomach dump by a gastric lavage, followed by the administration of cathartics and activated carbon. Inducing vomiting is another option to purge the stomach, but if large amounts of taxine have been absorbed this has the risk of triggering nervous and cardiac system complications, after the gastric lavage it may be necessary to examine the gastric contents for yew leaves and submit samples for taxine determination.

It is also important to control the blood pressure and the heart rate to treat the heart problems. Atropine has been used successfully in humans to treat barycardias and arrithymias caused by taxine. It is more effective if administrated early, but it is also necessary to be cautious with the administration because it can produce an increase in myocardial oxygen demand and potentiate myocardial hypoxia and dysfunction. An artificial cardiac pacemaker can also be installed to control the heartbeat.

Other treatments are useful to treat the other symptoms of poisoning: positive pressure ventilation if respiratory distress is present; fluid therapy to support blood pressure and maintain hydration and renal function; gastrointestinal protectants; and it may also be necessary to control aggressive behaviour and convulsions with tranquilizers.[13]

Prevention[edit]

The toxic effects of T. baccata have been known since ancient times. In most cases, poisoning is accidental, especially in cases involving children or animals. However, there are cases in which the poison is used as a suicide method.[14]

Because taxine poisoning is often only diagnosed after the death of the patient due to its rapid effect, preventing exposure is very important. Even dried parts of the plant are toxic because they still contain taxine molecules. Pet owners must ensure that yew branches or leaves are not used as toys for dogs or as perches for domestic birds.

Toxicity in animals[edit]

The effects of Taxine in humans are very similar to the effects on animals, it has the same mechanisms of action, and most of the times the ingestion of yew material is diagnosed with the death of the animal. Moreover, clinical signs, diagnosis, treatment and prevention are mostly the same as in humans, this was seen due to the many experiments realized on rats, pigs… [15]

However, there are some animals that are immune to the effects of taxine such macaws and white-tail deer.

Mechanism of action[edit]

The toxicity of the yew plant is due to some substances that are found in it, the principal ones are: toxic alkaloids (taxine B, paclitaxel, isotaxine B, taxine A), glycosides (taxicatine) and taxane derivates (taxol A, taxol B).[16]

There have been a lot of studies about the toxicity of the taxine alkaloids[17][18] and they have shown that their mechanism of action is interfering with the sodium and calcium channels of the myocardial cells, increasing the cytoplasmic calcium concentrations, their mechanism is similar to drugs such as verapamil, although taxines are more cardioselective.[19] They also reduce the rate of the depolarization of the action potential in a dose-dependent manner, this produces bradycardia, hypotension, depressed myocardial contractility, conduction delay, arrhythmias… [20]

Some taxine alkaloids have been isolated to study its effects and characteristics, this has allowed to know some of the particular effects of each substance of the plant, for example: it showed that taxine A doesn’t influence in blood pressure, that taxol causes itself cardiac disturbances in some patients, and that taxine B is the most toxic substance.[21]

There has been a recent discovery in a molecule derived from the yew: paclitaxel, it has been proved that it functions as an anticancer drug, because of it there have been some investigations to show if taxine B could be also used as a pharmacodrug, but it hasn’t been proved yet.[22]

See also[edit]

References[edit]

  1. ^ "Taxine". Toxnet. NLM. 2009-01-05. 
  2. ^ Cazes, Jack (2005). Encyclopedia of Chromatography, Vol.2. Taylor & Francis Group. p. 1660. 
  3. ^ Wilson, C. R.; Sauer, J.; Hooser, S. B. (2001). "Taxines: A Review of the Mechanism and Toxicity of Yew (Taxus spp.) Alkaloids". Toxicon. 39 (2–3): 175–85. doi:10.1016/s0041-0101(00)00146-x. PMID 10978734. 
  4. ^ http://www.guidechem.com/reference/dic-409796.html
  5. ^ http://aspcapro.org/sites/pro/files/zk_vetm0905_646_650.pdf
  6. ^ http://www.thepoisongarden.co.uk/atoz/taxus_baccata.htm
  7. ^ http://aspcapro.org/sites/pro/files/zk_vetm0905_646_650.pdf
  8. ^ http://www.iucnredlist.org/details/42546/0
  9. ^ "Intoxicación por tejo". 
  10. ^ José Luis Hernández Hernández; Fernando Quijano Terán; Jesús González Macías (2010). "Intoxicación por tejo". Medicina Clínica. 
  11. ^ "Toxnet: Taxine". 
  12. ^ "MedlinePlus: Yew poisoning". 
  13. ^ R.B. Cope (September 2005). "The dangers of yew ingestion" (PDF). Veterinary Medicine. 
  14. ^ "Suicidal poisoning by ingestion of Taxus Baccata leaves. Case report and literature review" (PDF). Romanian Journal of Legal Medicine. XXI (2(2013)). 
  15. ^ http://aspcapro.org/sites/pro/files/zk_vetm0905_646_650.pdf
  16. ^ Ramachandran, Dr. Sundaram (2014). Heart and Toxins. p. 160. ISBN 9780124165953. 
  17. ^ "Taxine- Mechanism of action". PubChem. 
  18. ^ Tekol Y. "Negative chronotropic and atrioventricular blocking effects of taxine on isolated frog heart and its acute toxicity in mice". PubMed. 
  19. ^ Tekol Y; Göğüsten B. "Comparative determination of the cardioselectivity of taxine and verapamil in the isolated aorta, atrium and jejunum preparations of rabbits". PubMed. 
  20. ^ G. Barceloux, Donald (2008). Medical Toxicology of Natural Substances: Foods, Fungi, Medicinal Herbs, Plants, and Venomous Animals. p. 900. ISBN 9780471727613. 
  21. ^ Suffness, Matthew (1995). Taxol: Science and Applications. p. 311. 
  22. ^ Barbara Andersen, Karina (2009). "Future perspectives of the role of Taxines derived from the Yew (Taxus baccata) in research and therapy". Journal of Pre-Clinical and Clinical Research. 3 (1). 

Further reading[edit]

[1] Asheesh K. Tiwary, Birgit Puschner, Hailu Kinde, Elizabeth R. Tor (2005). "Diagnosis of Taxus (Yew) poisoning in a horse". Journal of Veterinary Diagnostic Investigation.

[2]Andrea Persico, Giuseppe Bacis, Francesca Uberti, Claudia Panzeri, Chiara Di Lorenzo, Enzo Moro, and Patrizia Restani (2011). "Identification of Taxine Derivatives in Biological Fluids from a Patient after Attempted Suicide by Ingestion of Yew (Taxus baccata) Leaves". Journal of Analytical Toxicology. Vol. 35