Taxine alkaloids

{{Chembox | Reference =  | Name = Taxine A | IUPACName = 2α,13α-Diacetoxy-7β,10β-dihydroxy-9-oxo-2(3→20)-abeotaxa-4(20),11-dien-5α-yl (2''R'',3''S'')-3-(dimethylamino)-2-hydroxy-3-phenylpropanoate | OtherNames = (1''R'',2''S'',3''E'',5''S'',7''S'',8''S'',10''R'',13''S'')-2,13-Diacetoxy-7,10-dihydroxy-8,12,15,15-tetramethyl-9-oxotricyclo[9.3.1.14,8]hexadeca-3,11-dien-5-yl (2''R'',3''S'')-3-(dimethylamino)-2-hydroxy-3-phenylpropanoate | data page pagename =  | ImageFile = Taxine A.svg | ImageClass = skin-invert-image | ImageSize = 220px | ImageAlt = Skeletal formula of Taxine A | ImageName = | ImageCaption = Taxine A | ImageNameR2 =  | SystematicName = | Section1 = {{Chembox Identifiers | 3DMet = | Abbreviations = | Beilstein = | CASNo = 1361-49-5 | CASNo_Ref = {{cascite|correct|CAS}} | CASNo_Comment = | UNII_Ref = {{fdacite|correct|FDA}} | UNII = ORV5NB1NST | ChEBI = 9417 | ChemSpiderID = 4445136 | EINECS = | EC_number = | EC_number_Comment = | Gmelin = | InChI = 1S/C35H47NO10/c1-18-24(44-19(2)37)15-23-26(45-20(3)38)14-22-17-35(6,32(42)30(40)28(18)34(23,4)5)27(39)16-25(22)46-33(43)31(41)29(36(7)8)21-12-10-9-11-13-21/h9-14,23-27,29-31,39-41H,15-17H2,1-8H3/b22-14+/t23-,24-,25-,26-,27-,29-,30+,31+,35-/m0/s1 | InChIKey = KOTXAHKUCAQPQA-MCBQMXOVSA-N | KEGG = C10619 | MeSHName = | PubChem = 5281829 | RTECS = | SMILES = CC1=C2C(C(=O)C3(CC(=CC(C(C2(C)C)CC1OC(=O)C)OC(=O)C)C(CC3O)OC(=O)C(C(C4=CC=CC=C4)N(C)C)O)C)O | UNNumber = }} | Section2 = {{Chembox Properties | AtmosphericOHRateConstant = | Appearance = | BoilingPt = | BoilingPtC = | BoilingPt_ref = | BoilingPt_notes = | Density = | Formula = C35H47NO10 | HenryConstant = | LogP = | MolarMass = 641.751 g·mol−1 | MeltingPt = 204-206 °C<ref name="Graf 376–381">{{Cite journal|last1=Graf|first1=Engelbert|last2=Kirfel|first2=Armin|last3=Wolff|first3=Gerd-Joachim|last4=Breitmaier|first4=Eberhard|date=1982-02-10|title=Die Aufklärung von Taxin A ausTaxus baccata L.|journal=Liebigs Annalen der Chemie|language=en|volume=1982|issue=2|pages=376–381|doi=10.1002/jlac.198219820222|issn=0170-2041}}</ref> | MeltingPtC = | MeltingPt_ref = | MeltingPt_notes = | pKa = | pKb = | Solubility = | SolubleOther = | Solvent = | VaporPressure = }} | Section3 = | Section4 = | Section5 = | Section6 = }}

{{ Chembox | Name = Taxine B | Reference =  | ImageFile = Taxine B.svg | ImageName = | ImageSize = 220px | ImageAlt = Skeletal formula of Taxine B | ImageCaption = Taxine B | OtherNames = | IUPACName = 10β-Acetoxy-1,2α,9α-trihydroxy-13-oxotaxa-4(20),11-dien-5α-yl (3''R'')-3-(dimethylamino)-3-phenylpropanoate | PIN = | SystematicName = | Section1 = {{Chembox Identifiers | 3DMet = | Abbreviations = | Beilstein = | CASNo = 1361-50-8 | CASNo_Comment = | CASNo2 = 1361-51-9 | ChEBI = 134192 | ChemSpiderID = 8113891 | EINECS = | EC_number = | EC_number_Comment = | Gmelin = | InChI = InChI=1S/C33H45NO8/c1-18-23(36)17-33(40)29(38)27-19(2)24(42-25(37)16-22(34(7)8)21-12-10-9-11-13-21)14-15-32(27,6)30(39)28(41-20(3)35)26(18)31(33,4)5/h9-13,22,24,27-30,38-40H,2,14-17H2,1,3-8H3 | InChIKey = XMZFIBDTPOUHMW-UHFFFAOYSA-N | KEGG = C19989 | MeSHName = | PubChem = 121443 | RTECS = | SMILES = CC1=C2C(C(C3(CCC(C(=C)C3C(C(C2(C)C)(CC1=O)O)O)OC(=O)CC(C4=CC=CC=C4)N(C)C)C)O)OC(=O)C | UNNumber = }} | Section2 = {{Chembox Properties | AtmosphericOHRateConstant = | Appearance = | BoilingPt = | BoilingPtC = | BoilingPt_ref = | BoilingPt_notes = | Density = | Formula = C33H45NO8 | HenryConstant = | LogP = | MolarMass = 583.722 g·mol−1 | MeltingPt = 115 °C | MeltingPtC = | MeltingPt_ref = | MeltingPt_notes = | pKa = | pKb = | Solubility = | SolubleOther = | Solvent = | VaporPressure = }} | Section3 = {{Chembox Structure | Coordination = | CrystalStruct = | MolShape = }} | Section4 = {{Chembox Thermochemistry | DeltaGf = | DeltaHc = | DeltaHf = | Entropy = | HeatCapacity = }} | Section5 = {{Chembox Explosive | ShockSens = | FrictionSens = | DetonationV = | REFactor = }} | Section6 = | Section7 = {{Chembox Hazards | AutoignitionPt = | ExploLimits = | FlashPt = | LD50 = | LC50 = | MainHazards = | NFPA-F = | NFPA-H = | NFPA-R = | NFPA-S = | PEL = | REL = | ExternalSDS = | GHSPictograms = | GHSSignalWord = | HPhrases = | PPhrases = }} | data page pagename =  }}

'''Taxine alkaloids''', which are often named under the collective title of taxines, are the toxic chemicals that can be isolated from the yew tree.<ref>{{Cite book|title=Veterinary toxicology: basic and clinical principles|date=2012|publisher=Academic|others=Gupta, Ramesh C. (Ramesh Chandra), 1949-|isbn=978-0-12-385926-6|edition= 2nd|location=Oxford|oclc=778786624}}</ref><ref>{{Cite journal|last=Miller|first=Roger W.|date=July 1980|title=A Brief Survey of Taxus Alkaloids and Other Taxane Derivatives|journal=Journal of Natural Products|language=EN|volume=43|issue=4|pages=425–437|doi=10.1021/np50010a001|bibcode=1980JNAtP..43..425M |issn=0163-3864}}</ref> The amount of taxine alkaloids depends on the species of yew, with ''Taxus baccata'' and ''Taxus cuspidata'' containing the most.<ref name=":0" /> The major taxine alkaloids are taxine A and taxine B although there are at least 10 different alkaloids.<ref>{{Cite book|title=Veterinary medicine: a textbook of the diseases of cattle, horses, sheep, pigs and goats|last=Constable|first=Peter D|others=Hinchcliff, Kenneth W. (Kenneth William), 1956-, Done, Stanley H.,, Grünberg, Walter,, Preceded by: Radostits, O. M.|isbn=978-0-7020-7058-7|edition=11th|location=St. Louis, Mo.|oclc=962414947|date = 2016-10-25}}</ref> Until 1956, it was believed that all the taxine alkaloids were one single compound named taxine.<ref name=":0" />

The taxine alkaloids are cardiotoxins with taxine B being the most active.<ref name="ReferenceA">{{Cite journal|last1=Alloatti|first1=G.|last2=Penna|first2=C.|last3=Levi|first3=R. C.|last4=Gallo|first4=M. P.|last5=Appendino|first5=G.|last6=Fenoglio|first6=I.|date=1996|title=Effects of yew alkaloids and related compounds on guinea-pig isolated perfused heart and papillary muscle|journal=Life Sciences|volume=58|issue=10|pages=845–854|issn=0024-3205|pmid=8602118|doi=10.1016/0024-3205(96)00018-5}}</ref> Taxine alkaloids have no medical uses but Paclitaxel and other taxanes that can be isolated from yews have been used as chemotherapy drugs.<ref>{{Cite book|title=Navelbine® and Taxotère®: histories of sciences|last=Muriel|first=Le Roux|others=Gueritte, Françoise|isbn=978-0-08-101137-9|location=London|oclc=964620092|date = 2016-11-26}}</ref>

== Provenance == thumb|''Taxus baccata''<nowiki/>'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,{{cn|date=December 2024}} the fleshy covering of the seeds (berries). Concentrations vary between species, leading to varying toxicities within the genus. This is the case of ''Taxus brevifolia'' (Pacific yew) and ''Taxus baccata'' (English yew); ''T. baccata'' contains high taxine concentrations, 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.<ref name="aspcapro.org">{{Cite web |url=http://aspcapro.org/sites/pro/files/zk_vetm0905_646_650.pdf |title=Archived copy |access-date=2016-10-14 |archive-date=2018-10-08 |archive-url=https://web.archive.org/web/20181008131154/http://aspcapro.org/sites/pro/files/zk_vetm0905_646_650.pdf }}</ref> The poison remains dangerous in dead plant matter.<ref>{{Cite web|last=Robertson|first=John|date=2018|title=Taxus baccata, yew|url=http://www.thepoisongarden.co.uk/atoz/taxus_baccata.htm|archive-url=https://web.archive.org/web/20191116083824/http://www.thepoisongarden.co.uk/atoz/taxus_baccata.htm|archive-date=2019-11-16|website=THE POISON GARDEN}}</ref>

These species have distinctive leaves, which are needle-like, small, spirally arranged but twisted so they are two-ranked, and linear-lanceolate. They are also characterized by their ability to regenerate from stumps and roots.<ref name="aspcapro.org"/>

''Taxus'' species are found exclusively in temperate zones of the northern hemisphere.<ref>{{Cite journal|last1=Vanhaelen|first1=Maurice|last2=Duchateau|first2=Jean|last3=Vanhaelen-Fastré|first3=Renée|last4=Jaziri|first4=Mondher|date=January 2002|title=Taxanes in Taxus baccata Pollen: Cardiotoxicity and/or Allergenicity?|url=https://www.thieme-connect.de/DOI/DOI?10.1055/s-2002-19865|journal=Planta Medica|language=en|volume=68|issue=1|pages=36–40|doi=10.1055/s-2002-19865|pmid=11842324 |bibcode=2002PlMed..68...36V |s2cid=260283336 |issn=0032-0943|url-access=subscription}}</ref> In particular ''T. baccata'' is found all over Europe, as a dominant species or growing under partial canopies of deciduous trees. It grows well in steep rocky areas on calcareous substrates such as in the chalk downs of England, and in more continental climates it fares better in mixed forests. ''T. baccata'' is sensitive to frost, limiting its northern Scandinavian distribution.<ref>{{cite iucn|author=Farjon, A. |year=2013 |title=''Taxus baccata'' |errata=2017 |volume=2013 |article-number=e.T42546A117052436 |doi=10.2305/IUCN.UK.2013-1.RLTS.T42546A2986660.en |access-date = 15 January 2020 }}</ref>

== History == The toxic nature of yew trees has been known for millennia.<ref>{{Cite book|title=Alkaloids: Biochemistry, Ecology, and Medicinal Applications|last=F.)|first=Roberts, M. F. (Margaret|date=1998|publisher=Springer US|others=Wink, Michael.|isbn=978-1-4757-2905-4|location=Boston, MA|oclc=851770197}}</ref> Greek and Roman writers have recorded examples of poisonings, including Julius Caesar's account of Cativolcus, king of Eburones, who committed suicide using the "juice of the yew".<ref>{{Cite book|title=De bello Gallico VI|last=Julius.|first=Caesar|publisher=Bristol Classical Press, Dept. of Classics, University of Bristol|others=Kennedy, E. C. (Eberhard Christopher)|year=1982|isbn=978-0-86292-088-3|location=Bristol|chapter=31|oclc=12217646}}</ref> The first attempt to extract the poisonous substance in the yew tree was in 1828 by Piero Peretti, who isolated a bitter substance.<ref>{{Cite book|title=Alkaloids: Chemical and Biological Perspectives|volume = 11|last=Appendino|first=Giovanni|date=1996|publisher=Elsevier|isbn=978-0-08-042797-3|pages=237–268|doi=10.1016/s0735-8210(96)80006-9}}</ref> In 1856, H. Lucas, a pharmacist in Arnstadt, prepared a white alkaloid powder from the foliage of ''Taxus baccata L''. which he named taxine.<ref>{{Cite journal|last=Lucas|first=H.|date=1856|title=Ueber ein in den Blättern von ''Taxus baccata'' L. enthaltenes Alkaloid (das Taxin)|journal=Archiv der Pharmazie|language=en|volume=135|issue=2|pages=145–149|doi=10.1002/ardp.18561350203|s2cid=84660890|issn=0365-6233|url=https://zenodo.org/record/2291365}}</ref> The crystalline form of the substance was isolated in 1876 by W. Marmé, a French chemist. A. Hilger and F. Brande used elemental combustion analysis in 1890 to suggest the first molecular formula of {{chem2|C37H52NO10}}.<ref name=":0">{{Cite journal|last1=Wilson|first1=Christina R.|last2=Sauer|first2=John-Michael|last3=Hooser|first3=Stephen B.|date=2001|title=Taxines: a review of the mechanism and toxicity of yew (Taxus spp.) alkaloids|journal=Toxicon|volume=39|issue=2–3|pages=175–185|doi=10.1016/s0041-0101(00)00146-x|pmid=10978734|bibcode=2001Txcn...39..175W |issn=0041-0101}}</ref>

For the next 60 years, it was generally accepted that taxine was made of a single compound and it was well known enough for Agatha Christie to use it as a poison in A Pocket Full of Rye (1953). However, in 1956, Graf and Boeddeker discovered that taxine was actually a complex mixture of alkaloids rather than a single alkaloid.<ref>{{Cite journal|last=Graf|first=E|date=1956-04-07|title=Zur chemie des taxins|journal=Angewandte Chemie|language=de|volume=68|issue=7|pages=249–250|doi=10.1002/ange.19560680709|issn=0044-8249}}</ref> Using electrophoresis, they were able to isolate the two major components, taxine A and taxine B. taxine A was the fastest moving band and accounted for 1.3% of the alkaloid mixture, while taxine B was the slowest moving band and accounted for 30% of the mixture.<ref>{{Cite book|title=Veterinary Toxicology|last1=Wilson|first1=Christina R.|last2=Hooser|first2=Stephen B.|date=2007|publisher=Elsevier|isbn=978-0-12-370467-2|pages=929–935|doi=10.1016/b978-012370467-2/50171-1}}</ref> The full structure of taxine A was reported in 1982,<ref name="Graf 376–381"/> taxine B in 1991.<ref>{{Cite journal|last1=Ettouati|first1=L.|last2=Ahond|first2=A.|last3=Poupat|first3=C.|last4=Potier|first4=P.|date=September 1991|title=Révision Structurale de la Taxine B, Alcaloïde Majoritaire des Feuilles de l'If d'Europe, ''Taxus baccata''|journal=Journal of Natural Products|language=EN|volume=54|issue=5|pages=1455–1458|doi=10.1021/np50077a044|bibcode=1991JNAtP..54.1455E |issn=0163-3864}}</ref>

== Toxicity in humans == thumb|''Taxus baccata''<nowiki/>'s seeds thumb|3,5-Dimethoxyphenol molecule, used in the Taxine poisoning diagnosis alt=The molecular structure of Taxine B|thumb|The structure of Taxine B, the cardiotoxic chemical in the yew plant{{See also|Taxus baccata#Toxicity}} Almost all parts of ''Taxus baccata'', perhaps the best-known ''Taxus'' species, contain taxines.<ref name=":1">{{Cite book|last1=Garland|first1=Tam|title=Toxic plants and other natural toxicants|last2=Barr|first2=A. Catherine|date=1998|publisher=CAB International|others=International Symposium on Poisonous Plants (5th : 1997 : Texas)|isbn=0-85199-263-3|location=Wallingford, England|oclc=39013798}}</ref>

Taxines are cardiotoxic calcium and sodium channel antagonists.<ref>{{Cite journal|last1=Alloatti|first1=G.|last2=Penna|first2=C.|last3=Levi|first3=R.C.|last4=Gallo|first4=M.P.|last5=Appendino|first5=G.|last6=Fenoglio|first6=I.|date=1996|title=Effects of yew alkaloids and related compounds on guinea-pig isolated perfused heart and papillary muscle|journal=Life Sciences|volume=58|issue=10|pages=845–854|doi=10.1016/0024-3205(96)00018-5|issn=0024-3205|pmid=8602118}}</ref> If any leaves or seeds of the plant are ingested, urgent medical attention is recommended as well as observation for at least 6 hours after the point of ingestion.<ref>{{Cite web|title=TOXBASE - National Poisons Information Service|url=http://www.npis.org/toxbase.html|access-date=2019-09-05|archive-date=2020-11-20|archive-url=https://web.archive.org/web/20201120023000/https://www.npis.org/Toxbase.html}}</ref><ref>{{cite web|title=Taxus baccata - L.|url=https://pfaf.org/user/plant.aspx?LatinName=Taxus+baccata|access-date=2019-07-17|website=Plants for a Future}}</ref> There are currently no known antidotes for yew poisoning, but drugs such as atropine have been used to treat the symptoms.<ref>{{Cite book|last1=Wilson|first1=Christina R.|title=Veterinary Toxicology|last2=Hooser|first2=Stephen B.|date=2018|publisher=Elsevier|isbn=978-0-12-811410-0|pages=947–954|doi=10.1016/b978-0-12-811410-0.00066-0}}</ref> Taxine B, the most common alkaloid in ''Taxus'' species, is also the most cardiotoxic taxine, followed by taxine A.<ref name="ReferenceA" /><ref name="ReferenceB">{{Cite journal|last1=Smythies|first1=J.R.|last2=Benington|first2=F.|last3=Morin|first3=R.D.|last4=Al-Zahid|first4=G.|last5=Schoepfle|first5=G.|date=1975|title=The action of the alkaloids from yew (Taxus baccata) on the action potential in the Xenopus medullated axon|journal=Experientia|volume=31|issue=3|pages=337–338|doi=10.1007/bf01922572|pmid=1116544|s2cid=8927297}}</ref><ref name=":0" />

Taxine alkaloids are absorbed quickly from the intestine and in high enough quantities can cause death due to general cardiac failure, cardiac arrest or respiratory failure.<ref>{{Cite book|last1=Fuller|first1=Thomas C.|url=https://archive.org/details/bub_gb_0-op0XwlDmQC|title=Poisonous plants of California|last2=McClintock|first2=Elizabeth M.|date=1986|publisher=University of California Press|isbn=0-520-05568-3|location=Berkeley|oclc=13009854}}</ref> Taxines are also absorbed efficiently via the skin and Taxus species should thus be handled with care and preferably with gloves.<ref>Mitchell, A. F. (1972). ''Conifers in the British Isles''. Forestry Commission Booklet 33.</ref> Taxus Baccata leaves contain approximately 5 mg of Taxines per 1g of leaves.<ref name="ReferenceB" /> The estimated lethal dose (LDmin) of taxine alkaloids is approximately 3.0 mg/kg body weight for humans.<ref>{{Cite book|last1=Watt|first1=J.M.|title=Taxaceae. In The Medicinal and Poisonous Plants of Southern and Eastern Africa|last2=Breyer-Brandwijk|first2=M.G.|date=1962|publisher=Livingston|location=Edinburgh, UK|pages=1019–1022}}</ref><ref name="Kobusiak">{{cite journal|last1=Kobusiak-Prokopowicz|first1=Małgorzata|date=2016|title=A suicide attempt by intoxication with Taxus baccata leaves and ultra-fast liquid chromatography-electrospray ionization-tandem mass spectrometry, analysis of patient serum and different plant samples: case report|journal=BMC Pharmacol Toxicol|volume=17|issue=1|article-number=41|doi=10.1186/s40360-016-0078-5|pmc=5006531|pmid=27577698 |doi-access=free }}</ref> Different studies show different toxicities; a major reason is the difficulty of measuring taxine alkaloids.<ref name="Veterinary Toxicology">{{Cite book|last1=Clarke|first1=E.G.C.|title=Veterinary Toxicology|last2=Clarke|first2=M.L.|date=1988|publisher=Baillière, Tindall & Cassell|isbn=978-0-7020-1249-5|editor-last=Humphreys|editor-first=David John|edition=3rd|location=London|pages=276–277|chapter=Poisonous plants, Taxaceae}}</ref>

Minimum lethal doses (oral LDmin) for many different animals have been tested:<ref name="Veterinary Toxicology" />

* Chicken 82.5 mg/kg * Cow 10.0 mg/kg * Dog 11.5 mg/kg * Goat 60.0 mg/kg * Horse 1.0–2.0 mg/kg * Pig 3.5 mg/kg * Sheep 12.5 mg/kg

Several studies<ref>[https://www.nlm.nih.gov/toxnet/index.html TAXINE – National Library of Medicine HSDB Database, section "Animal Toxicity Studies"]</ref> have found taxine {{LD50}} values under 20 mg/kg in mice and rats.

=== Clinical signs ===

'''Cardiac and cardiovascular effects:'''

* Arrhythmia – Irregular heartbeats leading to lower cardiac output; itself a very severe symptom. Ventricular arrhythmias can lead to circulatory collapse (via cardiac arrest) very quickly if not treated. * Bradycardia – Fewer heart beats per time unit.

Both these effects lead to hypotension, which gives many symptoms including:

* Headache * Dizziness * Tremor and many other typical signs of low blood pressure.

'''Intestinal effects:'''

* Nausea and vomiting * Diarrhoea * Abdominal pain

'''Respiratory effects:'''

* Respiratory distress – Shortness of breath.

'''If the poisoning is severe and not treated:''' * Loss of consciousness – Lack of oxygen due to low blood pressure and respiratory distress forces the body to shut down all but the most vital functions. * Respiratory failure – Breathing stops. * Circulatory collapse – Blood pressure drops to the point that not even the most basic functions can be sustained. <ref>{{Cite web|url=https://www.nlm.nih.gov/toxnet/index.html|website=Toxnet |title=Taxine}}</ref><ref>{{Cite web|url=https://medlineplus.gov/ency/article/002877.htm|website=MedlinePlus |title=Yew poisoning}}</ref><ref>{{Cite web|url=https://www.promedmail.org/post/20110222.0578|access-date=25 January 2016|date=22 February 2011|title=PLANT POISONING, CERVID - USA: (ALASKA) ORNAMENTAL TREE, MOOSE|website=ProMED-mail}}</ref>

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

It is also important to control blood pressure and heart rate to treat the heart problems. Atropine has been used successfully in humans to treat bradycardias and arrhythmias caused by taxine. It is more effective if administered early, but it is also necessary to be cautious with 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, and gastrointestinal protectants. It may also be necessary to control aggressive behaviour and convulsions with tranquilizers.<ref>{{Cite journal|last=R.B. Cope|date=September 2005|title=The dangers of yew ingestion|url=http://aspcapro.org/sites/pro/files/zk_vetm0905_646_650.pdf|journal=Veterinary Medicine|access-date=2016-10-14|archive-date=2018-10-08|archive-url=https://web.archive.org/web/20181008131154/http://aspcapro.org/sites/pro/files/zk_vetm0905_646_650.pdf}}</ref>

=== Prevention === 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.<ref>{{Cite journal|title=Suicidal poisoning by ingestion of Taxus Baccata leaves. Case report and literature review|url=https://www.rjlm.ro/system/revista/26/115-118.pdf|journal=Romanian Journal of Legal Medicine|volume=XXI|issue=2(2013)}}</ref>

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 ==

The effects of Taxine in humans are very similar to the effects on other 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, and other animals.<ref name="aspcapro.org"/>

Poisoning is typically caused by ingestion of decorative yew shrubs or trimmings thereof. In animals the only sign is often sudden death. Diagnosis is based on knowledge of exposure and foliage found in the digestive tract. With smaller doses, animals display uneasiness, trembling, dyspnea, staggering, weakness, and diarrhea. Cardiac arrhythmias worsen over time, eventually causing death. "Necropsy findings are unremarkable and nonspecific", generally including pulmonary, hepatic, and splenic congestion. With lower doses, mild inflammation may be seen in the upper gastrointestinal tract.<ref name=":1" />

Some animals are immune to the effects of taxine, particularly deer.<ref name=":1" />

== Mechanism of action == The toxicity of the yew plant is due to a number of substances, the principal ones being toxic alkaloids (taxine B, paclitaxel, isotaxine B, taxine A), glycosides (taxicatine) and taxane derivates (taxol A, taxol B).<ref>{{Cite book|title=Heart and Toxins|last=Ramachandran|first=Dr. Sundaram|year=2014|isbn=978-0-12-416595-3|pages=160|publisher=Elsevier Science }}</ref>

There have been many studies about the toxicity of the taxine alkaloids,<ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/6433563|title=Taxine- Mechanism of action|website=PubChem}}</ref><ref>{{Cite journal|last=Tekol Y|title=Negative chronotropic and atrioventricular blocking effects of taxine on isolated frog heart and its acute toxicity in mice|journal=Planta Medica|volume=51|issue=5|pages=357–60|pmid=17342582|year=1985|doi=10.1055/s-2007-969519|bibcode=1985PlMed..51..357T |s2cid=33600321 }}</ref> and they have shown that their mechanism of action is interference with the sodium and calcium channels of myocardial cells, increasing the cytoplasmic calcium concentrations. Their mechanism is similar to drugs such as verapamil, although taxines are more cardioselective.<ref>{{Cite journal|last1=Tekol Y|last2=Göğüsten B|title=Comparative determination of the cardioselectivity of taxine and verapamil in the isolated aorta, atrium and jejunum preparations of rabbits|journal=Arzneimittelforschung|volume=49|issue=8|pages=673–8|pmid=10483513|year=1999|doi=10.1055/s-0031-1300481|s2cid=13312331 }}</ref> 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, and other complications.<ref>{{Cite book|title=Medical Toxicology of Natural Substances: Foods, Fungi, Medicinal Herbs, Plants, and Venomous Animals.|url=https://archive.org/details/medicaltoxicolog00barc|url-access=limited|last=G. Barceloux|first=Donald|year=2008|isbn=978-0-471-72761-3|pages=[https://archive.org/details/medicaltoxicolog00barc/page/n909 900]|publisher=John Wiley & Sons }}</ref>

Some taxine alkaloids have been isolated to study their effects and characteristics. This has allowed the discovery of some of the particular effects of each substance of the plant. For example, taxine A does not influence blood pressure, taxol causes cardiac disturbances in some people, that taxine B is the most toxic of these substances.<ref>{{Cite book|title=Taxol: Science and Applications|last=Suffness|first=Matthew|year=1995|page=311}}</ref>

Because a derivative from the yew, paclitaxel, functions as an anticancer drug, there have been investigations to show whether taxine B could also be used as a pharmaceutical.<ref>{{Cite journal|last=Barbara Andersen|first=Karina|year=2009|title=Future perspectives of the role of Taxines derived from the Yew (Taxus baccata) in research and therapy|journal=Journal of Pre-Clinical and Clinical Research|volume= 3| issue = 1}}</ref>

== See also == * Taxane * Taxadiene * Omacetaxine

== References == {{reflist}}

== Further reading == [http://vdi.sagepub.com/content/17/3/252.full.pdf] {{Webarchive|url=https://web.archive.org/web/20140509201820/http://vdi.sagepub.com/content/17/3/252.full.pdf |date=2014-05-09 }} Asheesh K. Tiwary, Birgit Puschner, Hailu Kinde, Elizabeth R. Tor (2005). "Diagnosis of Taxus (Yew) poisoning in a horse". ''Journal of Veterinary Diagnostic Investigation.''

[http://jat.oxfordjournals.org/content/35/4/238.full.pdf]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

Category:Taxanes