veterinary botany seminars, 2020 · cyanogenic glycosides produced by plants plant species...

Veterinary botany – Seminars, 2020 4. Plants containing HCN, or affecting heart functions

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 respiration

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

Plant species containing cyanogenic glycosides (CGs)

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

Polyphyletic origin of cyanogenic

glycoside production (colored) in

vascular plants

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)

HCN is catabolized in tissues

urinal excretion

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

Height: up to 1.5-2 m

With rhizome

Thickness of leaves: 1-2 cm


Hulls (green, later become violet) with a rounded apex

Spikelets, arranged in a nodding panicle, with 8-10 florets


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


Inflorescence: a racemose corymb

Flowers with five petals and five yellow anthers

Inflores- cence become nodding when the berries ripen


Cultivated for food industry


Sambucus ebulus – dwarf elderberry

Origin: Europe, Anatolia

Perennial

On soils rich in nutrients (nitrogen)


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


Odd pinnate compound leaves

With rhizome

Inflorescence: a racemose corymb


Black anthers and berries

Five petals

With an unpleasant smell

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

Plant species affecting heart functions

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

Plant species containing cardenolides

γ-lactone

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

Purple foxglove cultivars

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.)


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)


• Highest toxin contents at flowering stage

• LD 2 g (for humans); for horse: over 10% in hay

• Similar symptoms as that of Digitalis poisoning


adonitoxin

Adonis aestivalis - summer pheasant’s eye

A weed in wheat fields (rarely on pastures)

Sometimes its leaves can be found in hay


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

Lily-of-the-valley cultivars

Convallaria poisoning • Toxic agents are cardenolides:

e.g., convallatoxin, convalloside


• 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)


LD50 (cat): 0.07 mg/kg bw (i.v)

convallatoxin

convalloside

a

a

a

a

b

b

b

b

CONVALLARIA MAJALIS (a) vs. Allium ursinum (b)

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

Capsules with many flat, brown seeds


Seeds with a hairy pappus


• 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


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

two heterocycles

Plant species containing cardenolide derivatives

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.

Plant species containing bufadienolides

δ-lactone

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



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

Helleborus cultivars

Other plant species producing bufadienolides

• Drimia maritima (Asparagaceae) – sea squill

• Contains scillaren and proscillaridin

• Rodenticide plant

Plant species containing diterpene derivatives

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

♀ ♂


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


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.


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.


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.

veterinary botany seminars, 2020 · cyanogenic glycosides produced by plants plant species...

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