Veterinary botany Seminars, 2020 · Cyanogenic glycosides produced by plants Plant species...
Transcript of Veterinary botany Seminars, 2020 · Cyanogenic glycosides produced by plants Plant species...
Peeping into the second test
Species name in Latin 2
40% Species name in English 1
Family name in Latin 1
Habitat (where does the plant species live?)
1
60%
Type (chemical group) of poisonous compound(s)
1
Poisonous compound(s) 1
Specific symptoms caused by the plant species
3
Points
Σ 10 points/species (10 species/test; 100 points in total)
For each species, the Latin, or English name must be fulfilled to get points for the other questions
• In nature, many plant species produce specific defense compounds (secondary metabolites) to deter herbivores
• Consuming plants, animals may experience negative effects ranging from mild discomfort to death
• Even a small part of a strongly poisonous plant can induce disorders, or pathological changes
• Especially germinating or young (the more vulnerable) plant individuals contain high levels of poisons it is often decreased with age
"All things are poison and nothing is without poison; only the dose permits something not to be poisonous.„
Paracelsus (the founder of toxicology) 1530 AD
About plant poisonings in general
Accidental poisonings in the UK: ~ 0.3% of total deaths in 2010
of this, 5-10% were caused by plants
No data available regarding animals
The importance of plant
poisonings
Total deaths in 2010
(all causes, all ages)
493,242 (+0.4% in 2009)
England and Wales
accidental poisonings: 1,523
Accidental poisonings, detailed
Shamans used poisonous plants for tribal rituals
All over the world, poisonous plants were used to make arrow poisons or deter predators (Aconitum)
Theophrastus of Eresus („father of botany”): Historia Plantarum (287 BC) – descriptions of poisonous and medicinal plants
Plinius Secundus: Naturalis historiae (AD 77) – mentions 7000 species of poisonous plants
Plant poisons were often used to commit murders, suicide (Trial of Socrates) or carry out executions (Emperor Nero)
Poisonous plants in human history
Toxic compounds can be classified into categories
Commonly used terms Oral lethal dose (mg/kg bw)
Extremely toxic 1 or less (a few drops or a taste for an average built man)
Highly toxic 1-50 (4 ml, 1 teaspoon)
Moderately toxic 50-500 (30 ml, 1 spoon)
Slightly toxic 500-5000 (600 ml, 1 pint)
Practically non-toxic 5000-15,000 (1 litre)
Relatively harmless 15,000, or more (more than 1 litre)
Median lethal dose LD50 (mg/kg bw): the dose required to kill half the members of a tested population after a specified test duration.
Stephania tetrandra „fen fang ji“
in dietetic tea mixtures
contains a nephrotoxin an aristolochic acid
Sometimes humans get poisoned by plants • Kids, playing with plants, „try to eat
everything” colorful berries • Adults sometimes try out self-
treatments, alternative foods or misidentify plant taxa
• More rarely, plants are eaten to commit suicide
meadow saffron
lilly- of- the- valley
wild garlick
Aristolochia fangchi „guang fang ji“
Grazing animals
– changes in plant species compositions (abandonment of pastures)
– increased abundancy of poisonous plant species (mainly weeds)
– animal species have different tolerance levels against poisons
Animals kept in stables
– poisonous plants can be admixed in hay, meal or oil cake
– moldy forage
Pets
– left home alone get bored play with poisonous indoor plants
Animals get poisoned by plants: reasons
• Animals avoid poisonous plants instinctively selective preference of certain plant species
• Starving individuals are less selective
• Domesticated animals, fed with meals and forage mixtures, have no possibility to select
• Upon long-term poisoning with low doses, animals can develop tolerance against certain plant poisons or suffer of a chronic poisoning
Poisonings depend on the:
• dose of poisons consumed • type of plant organs and age of plants eaten • preparation methodology of forage (drying, ensilage) • species identity, age, gender or general health conditions
of animal individuals
Plant poisonings in animals
Poisoning must be suspected when...
• a new forage is invented or a new pasture is introduced and several animal individuals show the same or very similar symptoms
• pieces of poisonous plants, spat out, cover the ground
• clinical symptoms corroborate with the symptoms of a supposed poisoning
• remnants of poisonous plants in large quantities can be found in the intestines of the dead animal
amino acids, nucleic acids
Photo-syn-thesis
Cellular respi- ration
Termi- nal oxi-dation
Glycolysis
sesquiterpenoids
Plant primary and secondary metabolism
shikimic acid cinnamic acid
gallic acid
universal fatty acids
malonyl-CoA
isoprene
diterpenoids
monoterpenoids
monosaccharides (sugars) polysaccharides
oligosaccharides
SACCHARIDES
lignoids
flavonoids
coumarins
quinones
phenolic glycosides
tannins PHENOLOIDS
cyanogenic glycosides
alkaloids
glucosinolates
AZOTOIDS
specific polyketides
specific fatty acids
POLYKETIDES
tetraterpenoids
triterpenoids
polyterpenoids
steroids saponins
TERPENOIDS FATTY ACID metabolism
NITROGEN metabolism
CARBOHY-DRATE
metabolism
Calvin cycle
sugars
pyruvate
Citric acid cycle
acetyl-CoA
CO2
About glycosides in general
A glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond
The sugar group is then called glycone and the non-sugar part is aglycone
aglycone (here: salicylic alcohol)
glycone (here: glucose)
• CGs are produced from amino acids
• Ca. 60 types of CGs are known
Molecular origin of cyanogenic glycosides
phenylalanine
tyrosine
valine
isoleucine
prunasin
dhurrin
linamarin
lotaustralin
Biological function of CGs
heterodendrin
• In plant tissues, CGs are stored in vacuoles in inactive forms
• Upon plant injury, specific enzymes remove the sugar moiety
• Aglycones are activated; HCN is often released spontaneously
lotaustralin linamarin
sambunigrin dhurrin
amygdalin
triglochinin
HCN: mechanism of action
In animals, HCN can easily enter the tissues via mucous membranes (of the respiratory system and gastrointesti-nal tract) or from the skin surface
HCN inhibits the cytochrome C oxidase enzyme (the last enzyme in the respiratory electron transport chain located in the mitochondrial inner membrane) inhibi-tion of cellular respiration (histotoxic hypoxia) no more ATP (energy) is produced death
Cytochrome C oxidase translocates H+ across the mem-brane to establish a transmembrane difference of H+ electrochemical potential:
4 Fe2+-cytochrome C + 8 H+in + O2 → 4 Fe3+-cytochrome C
+ 2 H2O + 4 H+out
HCN: mechanism of action
The cytochrome C oxidase complex (entire view) In the active
site: O2 is prepared to produce H2O
CN- ion binds to Fe2+ ion and makes active site inactive
Hydrogen cyanide toxicity: symptoms
• 15-20 minutes (1 hour) after CG containing plants are eaten:
- blood, mucous membranes (and skin) of cherry color; clotting of blood is slow
- nausea, vomiting, breath with smell of bitter almond - heavy breathing - muscle contraction, spasms - stumbled walk, coma, death
• Symptoms last for 30-60 minutes
• After 2 hours, there is a good chance of survival
HCN is a toxic compound for animals, plants and even for fungi (for each organism using O2 as final electron acceptor in the respiratory electron transport chain)
In humans, pH is too low in the stomach and too high in the small intestine to provide a suitable environment for HCN release humans are less sensitive to HCN compared to ruminants
Acute poisoning: 20 mg of HCN in 100 g green plant
High temperatures and droughts increase HCN levels in plants
Burning of silk, wool, polyurethane or nylon HCN is released
Hydrogen cyanide toxicity
LD50 of CGs: 50-300 mg/kg bw (human)
LD50 of HCN: 0.5-2.5 mg/kg bw (human)
Chemical proof of the presence of CGs Guignard’s reaction (Léon Guignard, French pharmacist)
• A white filter paper is soaked in picric acid (yellow) solution; neutralization with a NaHCO3 solution
• 2-3 leaves, grinded by a glass rod, are put into a test tube; a few drops of water and 0.5 ml of 3N HCl solution are added
• Filter paper with picric acid is closed into the test tube for 2 h at 40 °C
• The color of filter paper turns red (sodium isopurpu-rate is produced); the darker the red color is, the higher is the content of HCN in the plant tissue
Origin: Europe
Perennial
In swamps on river banks; planted in garden ponds
Young stems are poisonous
Edible grains for mush
CG: triglochinin
Poaceae – grass family
GLYCERIA MAXIMA – reed sweet grass
Hulls (green, later become violet) with a rounded apex
Spikelets, arranged in a nodding panicle, with 8-10 florets
GLYCERIA MAXIMA – reed sweet grass
Reed sweet grass poisoning in cattle
Aboling et al. 2014. Case Report: Complex Plant Poisoning in Heavily Pregnant Heifers in Germany. J. Veterinar. Sci. Technolo. 5 (3) 100017.
Cattle were brought to a new pasture and ate reed sweet grass
Symptoms
They stopped feed intake and became apathetic
Haemorrhagic enteritis
Photodermatoses both on mouth and vulva
Blood samples were positive for CG 0.17-1.56 mg cyanide / 1 litre serum mortality: 80%
PRUNUS TENELLA (syn. AMYGDALUS NANA) – dwarf Russian almond
Origin: Eurasia
Perennial
In habitats with loessy soil; also in dolomite rock grasslands, gardens, parks
The whole plant is poisonous
CGs: prunasin, amygdalin
Red-listed (endangered) in Hungary
Rosaceae – rose family
amygdalin
PRUNUS TENELLA – dwarf Russian almond
Dwarf shrub up to 1 m height
With stone fruits up to 1-2 cm in diameter
SAMBUCUS NIGRA – black elder
Distribution: Europe, N. America
Perennial shrub with woody stems
On soils rich in nutrients (nitrogen)
Its green parts are poisonous: contain sambunigrin (a CG); accumulate oxalate crystals in bark
Its ripe berries are edible (marmalade, food dye)
Starving sheep may consume poisoning
Adoxaceae – moschatel family sambunigrin
Up to 7 m height
Bark of young shoots with lenticels; spongy tissue inside
Odd pinnate compound leaves
SAMBUCUS NIGRA – black elder
Inflorescence: a racemose corymb
Flowers with five petals and five yellow anthers
Inflores- cence become nodding when the berries ripen
SAMBUCUS NIGRA – black elder
Sambucus ebulus – dwarf elderberry
Origin: Europe, Anatolia
Perennial
On soils rich in nutrients (nitrogen)
The whole plant is poisonous
Berries with a bitter taste con-tain ebulosid glycoside; aglycone: ebulin bound to a protein (altogether: it is a lectin) that inhibits ribosomal proteins (RIP)
Starving sheep may consume poisoning
Adoxaceae – moschatel family
Sambucus ebulus – dwarf elderberry
Odd pinnate compound leaves
With rhizome
Inflorescence: a racemose corymb
Effects of ebulins: a case study
In mice, ebulin F triggers specific derangement of the intestines
2.50
3.75 5.00
Jiménez et al. 2013. Toxicity in mice of lectin ebulin f present in dwarf Elderberry (Sambucus ebulus L.). Toxicon 61 26-29.
mg/kg body weight
Tropic plants of high importance containing CGs
• Manihot esculenta (Euphorbiaceae) cassava: linamarin
Tubers are shredded, dried, washed in running water, and cooked
• Bambusa vulgaris (Poaceae) bamboo: taxiphyllin
Cyanogenic glycosides produced by plants
Plant species Cyanogenic glycosides
Almond, apple, peach, apricot, cherry, cotoneaster, firethorn, dwarf almond (in their seeds)
amygdalin
Plum taxa (in seeds), cherry laurel, bracken fern
prunasin
Black elder sambunigrin
Yew taxiphyllin
Bird’s foot trefoil, flax, lima bean, white clover
lotaustralin, linamarin
Sorghum spp. dhurrin
Reed sweet grass, lords-and-ladies triglochinin
Mercurialis spp. (mercuries) heterodendrin
CG concentration in some common plants
• Malus domestica (apple, in seed): 30 mg/100 g
• Cotoneaster horizontalis (cotoneaster): 20 mg/100 g
• Pyracantha coccinea (scarlet firethorn): 12 mg/100 g
• Prunus spp. (in seed)
– P. armeniaca (apricot): 8 g/100 g
– P. persica (peach): 6 g/100 g
– P. domestica (plum): 2.5-6.0 g/100 g
– P. avium, P. cerasus (cherry, sour cherry): 2 g/100 g
– Amygdalus communis var. amara (bitter almond): less than 5 g/100 g
• Trifolium repens (white clover; wild) – 350 mg/100 g
Molecular origin of cardiac glycosides
squalene
lanosterol (C30H50O) with
steroid skeleton
cholesterol (C27H46O)
cardenolides (C23H34O2)
bufadienolides (C24H34O2)
γ-lactone
δ-lactone
• In cardiac glycosides, the aglycone is a steroid
• Both in animals and plants, steroid skeleton is biosynthesized from squalene (one of the most important triterpenes)
• Aglycones in cardiac glycosides can be classified into three groups: cardenolides, cardenolide derivatives, and bufadienolides
cardenolide derivatives (C27H46O)
• Potency in disrupting heart functions extremely toxic compounds for animals (mainly for mammals)
• In low amounts: applied to develop cardiac medicines
• In large doses: rhythm of the heart gets lost, ventricular tachycardia is ensued cardiac arrest fibrillation
• Bufotoxin, produced by Bufo spp. (toads), has the same effect
About cardiac glycosides in general
Bufotoxin poisoning: a case study
Barbosa et al. 2009. Toad poisoning in three dogs: case reports. J. Venom Anim. Toxins incl. Trop. Dis. 15 (4) 789-798.
• 3-year-old Rottweiler bit a toad; two hours later:
- intense salivation
- prostration
- dyspnea
- vomiting
- hemorrhagic diarrhea
- cardiac arrhythmia
- seizure episodes
• Electrocardiography revealed respiratory sinus arrhythmia and ventricular tachycardia
Cardiac glycosides: mechanism of action • Na+/K+ pumps in cell membranes
are inhibited increased Na+ levels within cardiac muscle (CM) cells
• Na+/Ca2+ exchangers (NCX, responsible to pump 1 Ca2+ out of the CM cell and let 3 Na+ in) also
got inhibited due to the raised levels of intracellular Na+ raised Ca2+ levels in CM cells
• Increased cytoplasmic Ca2+ levels cause increased Ca2+ uptake into the sarcoplasmic reticulum (SR)
• Raised Ca2+ stores in the SR allow a greater Ca2+ release on stimulation, so the (CM) cells can achieve faster and more powerful contractions (positive inotropic effect) decreased heart rate (negative chronotropic effect)
• Slow catabolism of cardiac glycosides
cardiac myocyte
Effects of cardiac glycosides detected on ECG
Symptoms
• acute heart failure
• ST depression best seen in leads V4, V5 and V6
• myocardial damages the electrical conduction system of heart is affected
• increased heart rate, weak pulse, irregular heartbeat
• death
Cardiac glycoside (Digitalis) poisoning: general symptoms
• Poisonings are rare: leaves (of D. grandiflora) with a strong bitter taste; induce spontaneous vomiting
• Consumption of 2-3 leaves can kill a human
• For a pig of 50 kg: 4-5 g of dry leaves can be lethal
• General symptoms
– after 1-2 hours: nausea, vomiting, disorders of color vision, hallucinations
– within 5-6 hours: decreased heart rate, cardiac arrhythmias, tremor, seizures, coma, death
• The higher the K+ level in blood, the stronger the poisoning (in humans; not true for animals)
• With a specific antidote
Chemical proofs of cardiac glycosides • Kedde test: mix the sample with
equal volumes of a 2% solution of 3, 5 dinitrobenzoic acid in menthol and a 7.5% aqueous solution of KOH. - Development of a blue or violet color that fades out in 1 to 2 hours proves the presence of cardenolides
https://www.youtube.com/watch?v=k8V6yI9IJ2Q
• Baljet test: take a piece of lamina or thick section of the leaf and add sodium picrate reagent. If glycosides (unsaturated lactones) are present, yellow to orange color will be seen
Plant species containing cardiac glycosides
Plant taxa
DIGITALIS spp. (Plantaginaceae)
ADONIS spp. (Ranunculaceae)
CONVALLARIA MAJALIS (Asparagaceae)
Nerium oleander (Apocynaceae)
Strophanthus gratus (Apocynaceae)
ASCLEPIAS spp. (Apocynaceae)
VINCETOXICUM HIRUNDINARIA (Apocynaceae)
HELLEBORUS spp. (Helleboraceae)
Cardiac glycosides (aglycones)
cardenolides
cardenolides
cardenolides
cardenolides
cardenolides
cardenolides
cardenolide derivatives
bufadienolides
DIGITALIS PURPUREA – purple foxglove
Distribution: continental Europe
Biennial
In acidophilous forests; many cultivars in gardens
Digitus (Latin): finger
Formerly a cultivated medicinal plant
Plantaginaceae – plantain family
DIGITALIS PURPUREA – purple foxglove
Velvety, lanceolate leaves
Height: 40-80 cm
Fused petals with dots of darker (red) colors inside
Digitalis poisoning • Toxic agents are
cardenolides: digitoxin, gitoxin, digoxin
• The whole plant is poisonous; more when dried
• In dry leaves: 0.5-1.5% of cardenolides in weight
• Proportions of toxins varies among plant individuals and cultivars
Lethal dose (green leaves) Horse: 100-140 g Cattle: 150-200 g Pig: 15-20 g Goat: 25-30 g
LD50 (cat): 0.45 mg/kg bw (intravenous)
LD50 (cat): 0.25 mg/kg bw (i.v.)
LD50 (cat): 0.65 mg/kg bw (i.v.)
digitoxin
gitoxin
digoxin
D. grandiflora – yellow foxglove
In semi-dry oak forests
Other Digitalis species
D. lanata – woolly foxglove
Leaves with white hairs
Fornaciari et al. 2015. A medieval case of digitalis poisoning: the sudden death of Cangrande della Scala, lord of verona (1291-1329). J. Archaeol. Sci. 54: 162-167.
A medieval case of Digitalis poisoning
Chamomile pollen Digitalis pollen
Stomach Liver
ADONIS VERNALIS – spring pheasant’s eye
Distribution: continental Europe
Perennial
On dry meadows, steppes (pastures)
Vernus (Latin): spring flowering
Red-listed in Hungary
Ranunculaceae – buttercup family
ADONIS VERNALIS – spring pheasant’s eye Shiny, black rhizome
Height: 10-40 cm
Leaves with deeply indented margins
Flowering: March-May
Fruit: achene
Poisoning: spring pheasant’s eye
• Toxic agents are cardenolides: e.g., adonitoxin
• Other amphiphilic compounds, such as ranunculin (see Seminar 6)
• The whole plant is poisonous; more when dried
• Highest toxin contents at flowering stage
• LD 2 g (for humans); for horse: over 10% in hay
• Similar symptoms as that of Digitalis poisoning
LD50 (cat): 0.19 mg/kg bw (i.v.)
adonitoxin
Adonis aestivalis - summer pheasant’s eye
A weed in wheat fields (rarely on pastures)
Sometimes its leaves can be found in hay
The whole plant is poisonous
Adonis aestivalis poisoning: a case study
Woods et al. 2004. Summer pheasant’s eye (Adonis aestivalis) poisoning in three horses. Vet. Pathol. 41: 215-220.
• Horses refused to eat the hay with A. aestivalis
• Irregular heart rate • Weakness • The horse was recumbent and in pain • No response to botulinum antitoxin, or
administration of activated charcoal • Euthanatized 4 days after first exhibiting clinical
signs
Fig. 1. Left ventricular free wall; horse No. 3. Dark foci (arrows) are foci of myocardial hemorrhage, necrosis, and collapse. Foci were most prominent in the left ventricular free wall and septum on gross examination. Fig. 2. Left ventricle; horse No. 1. Photomicrograph of the left ventricle with mild interstitial edema, neutrophilic infiltrates and myocardial necrosis. The arrows demonstrate contraction band necrosis and fragmentation of the sarcoplasm. HE. Bar _ 100 _m. Fig. 3. Left ventricle; horse No. 3. Left ventricle with large regions of myofiber collapse and satellite cell hypertrophy. HE. Bar _ 200 _m.
Adonis aestivalis poisoning: a case study
Distribution: continental Eurasia
Perennial
In forests, parks, and gardens
Majalis (Latin): flowering in May
Asparagaceae – asparagus family
CONVALLARIA MAJALIS – lily-of-the-valley
CONVALLARIA MAJALIS – lily-of-the-valley
Clonal plant with rhizomes
Always 2 broad, lanceolate leaves are produced
Flowers, with a pleasant odour, are arranged in a raceme
For September red fruits with 2-6 seeds
Convallaria poisoning • Toxic agents are cardenolides:
e.g., convallatoxin, convalloside
• The whole plant is poisonous; more when dried
• The highest toxin levels in the berries and seeds
• Flowers in a vase: toxins can be released into the water
• No accumulation of toxins in tissues
• LD50: 0.1-0.3 mg/kg bw (human, oral)
• Similar symptoms as that of Digitalis poisoning
LD50 (cat): 0.07 mg/kg bw (i.v)
convallatoxin
convalloside
Convallaria poisoning: a case study
Atkinson et al. 2008. Suspected lily-of-the-valley (Convallaria majalis) toxicosis in a dog. J. Vet. Emerg. Crit. Care 18 (4): 339-403.
Symptoms in dog
• bradycardia, lethargy
• defecation in the house
• vomitus with orange color
The owner was further questioned about the dog’s exposure to any plants that could contain cardiac glycosides.
The dog had been seen chewing the leaves of a plant that was later identified as lily-of-the-valley.
Atkinson et al. 2008. Suspected lily-of-the-valley (Convallaria majalis) toxicosis in a dog. J. Vet. Emerg. Crit. Care 18 (4): 339-403.
Convallaria poisoning: a case study
after the placement of a permanent transvenous pacemaker...
When the dog arrived to the hospital:
ASCLEPIAS SYRIACA – common milkweed Origin: N. America; invasive in Europe
About 150 Asclepias species worldwide
Perennial
Good pasture for honey bees
On disturbed grasslands; mainly on sandy soils
Not poisonous for many butterflies (e.g., for monarch butterfly) butterflies become toxic for birds
Apocynaceae – dogbane family
ASCLEPIAS SYRIACA – common milkweed
Oval leaves with an entire margin
Height: 150 cm
With a white milky sap
• Toxic agents are cardenolides: e.g., uzarigenin, syriogenin, syriosid, α, β asclepiadin
• The whole plant (even when dried) is poisonous; especially its milk
• Green plants are almost never nibbled but dry leaves in hay are dangerous
• LD (ruminants, horse): 0.005-2% of body weight
• Similar symptoms as that of Digitalis poisoning
Asclepias poisoning
uzarigenin
syriosid
syriogenin
Narrow-leaved Asclepias species
Mainly in N. America
Many of them contain no cardiac glycosides, but several neurotoxins
A. verticillata
A. pumila
• Strophanthus gratus, S. kombe (Apocynaceae) – climbing oleander strophanthidin with a mechanism of action similar to that of Digitalis toxins
• Nerium oleander (Apocynaceae) – oleander oleandrin (see Seminar 8)
Other plant species with cardenolides
VINCETOXICUM HIRUNDINARIA – white swallow-wort
Distribution: continental Eurasia
Perennial
In forests, on dry grasslands
Vincetoxicum (in Latin): „conqueror of poison” (antidote of other plant poisons and animal venoms it evokes strong vomiting)
Used as homeopathic medicines
Apocynaceae – dogbane family
VINCETOXICUM HIRUNDINARIA – white swallow-wort
Perennial plant with rhizomes, lanceolate leaves, pepper-like fruits (a follicle), and seeds having a hairy pappus
Flowering between May and August
Vincetoxicum poisoning
• Toxic agents are cardenolide derivatives, e.g., hirundigenin (the main component of vincetoxin)
• The highest poison levels are in the rhizomes
• The whole plant (even when dried) is poisonous for animals; especially sheep and dog are sensitive
• Similar symptoms as that of Digitalis poisoning but it needs 2-4 weeks to be fully developed
hirundigenin
Hess et al. 2014. A case of suspected swallow wort (Vincetoxicum hirundinaria) toxicity in a cat. J. Small Anim. Pract. 55: 386.
Vincetoxicum poisoning in a cat
A cat was presented because of an episode of acute collapse after chewing the dry leaves of swallow-wort: symptoms
• the cat was moribund (about to die), tachypnoeic
• hypothermic
• hypotensive
• bradycardic
• and had diarrhea and haematochezia (blood in its feces)
Treatment included stabilisation with oxygen, intravenous fluids, antibiotics and warming. The cat made a full clinical recovery after 48 hours.
HELLEBORUS PURPURASCENS – purple hellebore
Distribution: Europe
Perennial
In fresh forests, gardens
Elein (in Greek) – „to injure”, borá (in Greek) – „food” (the plant was put into the wells to make drinking water toxic)
Many cultivars
Ranunculaceae – buttercup family
HELLEBORUS PURPURASCENS – purple hellebore A clonal plant with black rhizomes
Digitate leaves
Bell-shaped, nodding flowers; fruit: follicle
Hellebore poisoning
• Toxic agents are bufadieno-lides, e.g., hellebrin and a dif-ferent compound, ranunculin, which is not a cardiac glyco-side (see Seminar 6)
• The whole plant (even when dried) is poisonous for animals
• The highest toxin levels are in the rhizome
• Toxins can be excreted into the milk; meat of poisoned animals is poisonous, too
• Similar symptoms as that of Digitalis poisoning
LD50 (cat): 0.08 mg/kg bw (i.v.)
Consumption of 3 mature follicles may lead to a serious toxicity
hellebrin
ranunculin
H. niger – black hellebore
An evergreen garden plant richest in bufadienolides
Other Helleborus species
Other plant species producing bufadienolides
• Drimia maritima (Asparagaceae) – sea squill
• Contains scillaren and proscillaridin
• Rodenticide plant
TAXUS BACCATA – yew An evergreen gymnosperm
Distribution: mainly in Europe (SW. Asia)
In mountainous forests and gardens
Diterpene alkaloids are taxines (e.g., taxine B)
Other Taxus species have taxanes (e.g., paclitaxel), which are used in oncological treatments (anticancer drugs)
Formerly used for making longbows
The Celts used it as an arrow poison, or to commit ritual suicide
Taxaceae – yew family
taxine B
paclitaxel (taxol)
Long-lived: 2000-3000 years old (Fortingall Yew; Perthshire, Scotland)
TAXUS BACCATA – yew
Height: 10–20 m
Trunk up to 2-3 m in diam.
Thin, scaly brown bark, coming off in small flakes
♀ ♂
TAXUS BACCATA – yew
Male cones are globose, 3–6 mm long
Seed cones are modified; each with a single seed
Leaves, 1-4 cm long, are arranged spirally on the stem, but the leaf bases are twisted to align the leaves in two flat rows
The aril (arillus) is not poisonous; it is gelatinous and very sweet
TAXUS BACCATA – yew
Birds and squirrels eat seed cones with aril seed dispersal
Taxus alkaloids: mechanism of action
Inhibition of Ca2+ and Na+ channels
Symptoms are similar to that ofDigitalis poisoning
Taxus poisoning
The whole plant (except the aril) is poisonous for all species
Hard seed coat dispersal by birds
No specific pathological changes; only indigested leaves in the intestines
Sensitive species: horse
Oral lethal doses of yew leaves in animals
Handeland 2008. Acute yew (Taxus) poisoning in moose (Alces alces). Toxicon 52: 829-832.
Orbell 2006. Fatal yew toxicity in beef heifers. Proc. of the Soc. of Sheep & Beef Cattle Vet. of the NZVA, pp 117-122.
Taxus poisoning: case studies
Acute yew (Taxus) poisoning in moose (Alces alces)
Calves died day by day: there were some Taxus trees on the unimproved pasture
Tiwary et al. 2005. Diagnosis of Taxus (Yew) poisoning in a horse. J. Vet. Diagn. Invest. 17: 252–255.
Taxus poisoning: case studies
A horse died due to Taxus poisoning: necrosis in cardiac muscle
Burcham et al. 2013. Myocardial fibrosis associated with previous ingestion of yew... J. Vet. Diagn. Invest. 25 (1): 147–152.
Taxus poisoning: case studies
Figure 1. Holstein calf. A, subgross view of 2 sections of myocardium with extensive myocardial fibrosis (asterisks). Red areas are viable myocardium; blue-tinged areas indicate early collagen deposition. Masson trichrome. Bar = 4 mm. B, loss of cardiac muscle fibers and replacement with fibroblasts and early collagen deposition (asterisks). Hematoxylin and eosin. Bar = 100 μm. C, loss of cardiac muscle fibers and replacement with fibroblasts and collagen fibers (red) as demonstrated with Picrosirius red. Bar = 100 μm. D, cardiac myofiber with nuclear rowing (arrow), indicating attempted myofiber regeneration. Adjacent myofibers are atrophied. Picrosirius red. Bar = 50 μm. E, epicardial surface of 1 section of myocardium. The surface is covered by activated mesothelial cells (arrows), indicating likely pericardial effusion secondary to heart failure. Bar = 100 μm.
Twenty-six 5-month-old Holstein calves were accidentally exposed to discarded clippings from yew bushes in July 2008. Several calves died within 24 hrs of exposure; however, 1 or 2 calves died every day or every other day for the following 18 days until 22 of the original 26 animals were dead. The last calf with known exposure to yew, a heifer, died 18 days after removal of the plant material from the pasture.