Myotoxic Plants - USDAMyotoxic Plants Thermopsis ... oleandrin, digitoxigenin, neriin, folinerin,...
Transcript of Myotoxic Plants - USDAMyotoxic Plants Thermopsis ... oleandrin, digitoxigenin, neriin, folinerin,...
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PPRL 2010
Poisonous Plant ClassADVS 586
Zane DavisBryan Stegelmeier
March 11, 2010
Myotoxic Plants
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PPRL 2010
Striated Muscle
Types of muscle
Mitochondria
Sarcolemna
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PPRL 2010
Ultrastructure
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PPRL 2010
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PPRL 2010
Striated Muscle Toxins•Larkspur (MLA block AchR)
•Monkshood (Aconitum inhibits Na channels)
•Botulism (cleaves synaptobrivin, syntaxin and SNAP-25 blocking cholinergic tx)
•Tetnus (tetanospasmin blocks glycine inhibition)
•Cardioglycosides (Inhibits Na/K ATPase enzyme)
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PPRL 2010
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PPRL 2010
Myotoxic PlantsMuscle structure and physiologyClinical and histologic lesionsMyotoxic Plants Thermopsis montana Eupathorium rugosum Haplopappus, Aplopappus or Isocoma spp. Cassia occidentalis O. obtusifolia Kwarwinskia humboldtiana Gossypium spp. Lathyrus spp. Vicia villosa Solanum spp. (enzootic calcification)
Cardioglycoside Containing Plants Digitalis purpurea Nerium oleander Convallaria majalis and C. montana Apocynum spp. Adonis aestivalis Pieris japonica and P. floribunda
Grayanotoxins Rhododendron spp. Kalmia spp.
Other potential myotoxic plants
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PPRL 2010
Clinical Signs
.
Anorexia, depression, droopy ears
Reluctant to stand or move
Swollen hard muscle
Walk with slow, labored gait
Weakness, trembling, ataxia
Recumbency, coma, death
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PPRL 2010
Biochemical Changes
ASTCPKKMyoglobinuriaSecondary changes
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PPRL 2010
Gross Lesion
Hard swollen musclesPale streaking in muscleSecondary changes Disuse atrophy Congestive heart failure Nephrosis Hepatic lipidosis
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PPRL 2010
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PPRL 2010
Histologic Lesions
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PPRL 2010
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PPRL 2010
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“Tremetol”-containing plants• Rayless Goldenrod
(Isocoma wrightii)• White Snakeroot(Eupatorium rugosum)
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Introduction• Caused “trembles” and “milk sickness” in humans since the early
1800s (death of Abraham Lincoln’s mother)• In 1930 the toxin was identified as tremetol• In 1960s tremetol was determined to be a mixture of alcohols
and ketones• Comprised of 4 major benzofuran ketone compounds
(tremetone, dehydrotremetone, 3-hydroxytremetone, and 3-oxyangeloyl-tremetone)
• Symptoms include depression, muscle weakness, reluctance to stand, and trembles especially following exercise
• Toxicity is sporadic
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White Snakeroot
PPRL 2010
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HPLC Chromatogram of Benzofuran compounds
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PPRL 2010
Compounds Concentration (µg/mg)
Collection Site Structure Numbers
1 2 3 4 5 6 7 8 9 10 11Illinois SitesStidham Woods 2.6 6.3 0.53Hart Woods 1.3 2.0 0.94Brownfield Woods 0.61 0.89Rutan Woods 0.86 5.7 0.99Larimore Property 4.7 2.7 0.53Interstate 2.0 0.079 0.43VRO 1.3 7.6 0.56Tonica 0.56 0.082 0.88Allerton Park 0.25 0.094 0.059 0.076 0.027Trelease Woods 0.12 0.062 0.036 1.0 0.61Missouri SitesDavies County 0.20 0.075 1.4 0.090 1.1Shooting Star Trail 0.21 0.32 0.052 0.010 0.17 0.039 1.3 0.047 0.69Karst Trailhead 0.28 0.59 0.30 0.058 0.23 0.16 2.2 0.47VMDL 0.19 0.34 0.066 0.33 0.079 0.58 0.040 0.27 0.55Evans Place 0.22 0.35 0.094 0.14 2.1 0.11 0.77 0.87Pierpont Meadows 0.16 0.16 0.056 0.050 2.4 0.10 0.59 0.44Indiana SiteWabash River 0.021 9.9Ohio SiteCincinnati Zoo 0.053 1.7
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PPRL 2010
Tremetol (mixture of tremetone, dehydroytremetone, dihydrotremetone and hydroxytremetone)Cytrochrome P450 activated and quickly detoxifiedGreen, dry and frosted plant are toxicLipid soluble results in relay of secondary toxicityStiffness, depression, ataxia, sternal recumbency, anorexia, tremors, coma, deathHorses develop CHF
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PPRL 2010
Disease in Livestock0.5-1.5% BW disease in 7-11 days6 month old hay toxicLactating cows protectedHistology Myonecrosis Hepatic lipidosis Hemorrhages and
congestion Gastroenteritis
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PPRL 2010
Jimmy Weed, Rayless Goldenrod, Burrow WeedIsocoma pluraflora (Isocoma wrightii),
(Haplopappus heterophyllus)An erect, sparsely branched, woody perennial growing to 1 meter highSticky leaves are linear and alternateYellow numerous flowers form small, terminal flat topped heads of 7 to 15 flowers
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PPRL 2010
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PPRL 2010
Alkaline soils of drier rangeland, river valleys, drainage areas, and irrigation canals TX, NM, AZ, and COHorses, cattle, sheep and goats1.5% bw toxic in cattle
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• 20 goats dosed via oral gavage for 7 days
• Treadmill evaluation of physical strength and endurance
• Electrocardiograms• Hematology and serum biochemistry • All animals were euthanized and the
lesions (muscle necrosis) were evaluated via light and electron microscopy, histochemistry and immunohistochemistry
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Recovery HR Resting HR CK AST LDH
Enzy
me A
ctivi
ty (U
/liter
)
0
5000
10000
15000
20000
25000%
Cha
nge i
n He
art R
ate
0
20
40
60
80
100
Day 3 Day 4 Day 5 Day 6 Day 7
Serum enzyme and heart rate changes of affected goats
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Muscles of affected goats
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PPRL 2010
Senna or Cassia spp.- coffee weed or coffee sena
Troublesome weeds southeastern United States, Hawaii, Mexico. Opportunist annuals that grow in waste areas, roadsides, fence lines. Common as weeds of corn and soybean fields.Green and dry plants are toxicPoison horses, cattle, sheep and goats.
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PPRL 2010
Cassia obtusifolia
Woody, erect, lightly branched annual, 2-3 m tallAlternate pinnate leaves with 4-5 pairs of leaflets spaced on common stalkFlowers are yellow in loose clusters on leaf axilsCurved seed pods (20 cm) are thick, dark brown and slightly flattened with with pale longitudinal stripes and brown seeds
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PPRL 2010
Most poisoning in cattle occurs in Nov. and Dec. after frosts. Calves are more susceptibleHorses may have liver disease sooner than the myonecrosis.Toxin is unknown but speculated to be substituted quinones- some evidence it uncouples oxidative phosphorylation. 0.4-12% BW toxic Skeletal and cardiac toxicityRecovery depends on the severity. Rarely does an animal recover once it has become recumbent.
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PPRL 2010
C. roemeriana, twin-leaf senna
30 to 70 cm tall principally on limestone soils in central and western Texas (yellow flower in spring and fall)
Toxin is unknown but likely a quinone type compound
Calves- hepatopathic poisoning, little-to- no skeletal muscle damage
Goats- mild-to-severe skeletal muscle damage, and mild hepatocellular injury
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PPRL 2010
Thermopsis montana of T. rhombifolia- Golden Banner, Mountain Thermopsis, False Lupine, Yellow Pea
A perennial pea like plant with a rhizomatous root system and erect, branching stems that reach a height of 30 to 46 cm. Alternate with three leaflets (lupine has 5+).Bright yellow flowers in dense racemes from the leaf axils Densely haired, erect seed pods that are straight (T. montana) or curved (T. rhombifolia).
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PPRL 2010
MO ID OR WA NE UT COQuinolizidine alkaloids: n-methylcytisine cytisine 5,6 dehydrolupamine thermopsine Anagyrine
1 g/kg BW for 2 to 4 days
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PPRL 2010
Signs and Lesions
Depression, weakness, trembling, recumbency and death
Edema, arched back, swollen eyelids
Increased serum enzymes
Muscle degeneration and necrosis
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PPRL 2010
Karwinskia humboldtianaCoyotillo, buckthorn, tanglefoot, tullidoraWoody shrub or small treeTX, Mexico and SW StatesGravely hills, canyons, and along arroyosPolyneuropathy with acending paralysisAnthracenones (T496, T514, T516, T544) usually called tullidinol and possibly other neurotoxinsInterfere with neuronal synthesis and axonal transport Large, long axons most severely affected
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PPRL 2010
Karwinskia humboldtiana
Cattle most sensitive but poisoning reported in goats, sheep, hogs, fowl, horses and man
Signs Lesions: Demyelinating
neuropathy, lymphadenopathy, epicardial hemorrhage, skeletal and myocardial degeneration and necrosis, nephrosis and lipidosis
Axoplasmal dysruption, wallerian degeneration, myelin degeneration
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PPRL 2010
Gossypol
Gossypium spp. (cotton plants)Polyphenolic binaphthalene found in the seedMonogastrics and young ruminants most susceptibleLesions CSM for several weeks Inappetence, weight loss,
weakness, ascietes, hydrothroax, CHF, skeletal and cardiac muscle degeneration and necrosis, regeneration
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PPRL 2010
Lathyrus spp.
Europe, Africa, Russia and IndiaPeople eat Lathyrus seedsL. hirsutus, L. incanus, L. pusillus, L. sylvestris, L. odoratus used in USHorses may be more susceptibleBeta-(gamma-L-glutamyl)-aminopropionitrileMetabolized to aminoproprionitrile that is thought to inhibit collagen cross linking (inhibits lysyl oxidase)Results in osteolathyrism and angiolathyrism- spinal cord and nerve degeneration, vasuclar aneurysms
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PPRL 2010
Cattle- stilted gait, weak, shift weight oftenHorses- severe weakness, laryngeal hemiplegia (roaring disease), lameness, sudden death
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PPRL 2010
Vicia villosa
Hairy vetchOK and midwestMyotoxin plus hepatotoxin, and neurotoxinGranulomatous inflammation in heart, skeletal muscle, adrenal glands, kidney, thryroid, brain and lungs (hypersensitivity ?)
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PPRL 2010
Cestrum diurnum
1,25-dihydroxycholecalciferolIncreases Ca absorption from GI, increases Ca mobilization from bone, decreases renal Ca excretionHypercalcemia and hyperphosphatemia- >60 product=soft tissue mineralizationCardiac, pulmonary, renal, and gastrointestinal mineralizationDystrophic calcification
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PPRL 2010
US Solanum spp.
S. verbascifolium, S. torvum, Nierembergia veitchii, Cestrum diurnum (jessamine, wild jasmine, day cestrum, king of the day, Chinese inkberry) FL
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PPRL 2010
Enzootic Calcification
Signs/Lesions: Chronic weight loss despite
normal appetite Stiffness » lameness »
recumbency Pain in the ligaments and
tendons Heart murmurs » failure Calcification of tendons,
ligaments, and elastic arteries » calcinosis of aorta, pulmonary arteries, heart valves, and endocardium
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PPRL 2010
Prognosis
Recovery is rare if poisoning is chronicLess severely poisoned animals will probably recover if they are denied further access to the plant and are given a balanced ration.
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PPRL 2010
Cardiac Glycoside Containing Plants
Digitalis (model compound)100-200 mg/kg lethal8% use results in toxicityBlocks Na/K ATPase causing increased intracellular Na and lowering the membrane potentialResulting increased Ca causes a positive ionotropic effectHigh doses interfere with the cardiac conduction system especially the SA and AV nodesAsystole
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PPRL 2010
Lesions (Cardiac Glycosides)
Arrhythmias (tachycardia), cold extremities, dilated pupils, blue mucous membranes, sweating, colic, anorexia, vomiting, diarrhea, bradycardia, heart block, asystole, and death.Minimal myocardial hemorrhage, myofiber vacuolation with minimal inflammation.
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PPRL 2010
Digitalis purpurea
FoxgloveBiennial herb from Europe, common on west coastDigtoxin, digoxin, gitoxinToxic green or when dry
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PPRL 2010
Nerium oleander
Ornamental throughout North AmericaEvergreen shrubNerioside, oleandroside, oleandrin, digitoxigenin, neriin, folinerin, oleandromycin, rosagenin, and odoroside that are similar to digitoxinToxic green and dryMost poisonings from clippings
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PPRL 2010
Convallaria majalis and C. montana
Lilly of the valleyOrnamental throughout North AmericaC. montana native to eastern USConvallarin, convallarmarin, convallatoxin (cardiac glycosides)All parts, green and dry are toxicSigns persist for 3 weeks including dermatitis and gastrointeritis
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PPRL 2010
Apocynum spp.
Dogbane, Indiana hempPerennial erect plant of North AmericaGreen and dry plant are toxicRoot used therapeutically
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PPRL 2010
Adonis aestivalis (Pheasant’s Eye)
Less toxic or more toxic?
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PPRL 2010
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PPRL 2010
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PPRL 2010
Rhododendron spp.
RhododendronDeciduous shrub found throughout North AmericaAndromedotoxin, grayanotoxin (Alters Na channels)Cattle, sheep, goats, rarely horses and people have been poisonedAll parts both green and dry are toxicGastroenteritis, colic, salivation, epiphora, anorexia, depression, nausea, vomiting, defecation, weakness, incoordination, paralysis, absent pupillary reflexes, coma, nephrosis, liver degeneration, aspiration pneumonia
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PPRL 2010
Kalmia spp.
LaurelsEvergreen shrubgrayanotoxin
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PPRL 2010
Pieris japonica and P. foribunda
Japanese PierisWoody shrubGrayanotoxin
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PPRL 2010
Other potentially myotoxic plants
Macadamia nuts- transient muscular weakness in dogsHops (Humulus lupulus)- malignant hyperthermia syndrome in dogsIxiolaena brevicompta- Austrialian plant causing tiring syndrome in sheepHelichrysum argyrophaerum- South AfricaGeigeria ornative- South AfricaCytisus scoparius- Scotch broom, leguminous shrub
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PPRL 2010
Disease of neglect
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PPRL 2010
Centauria spp.Centauria repens or Acroptilon repens (Russian knapweed)
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PPRL 2010
Creeping perennial with black horizontal rootsErect, rather stiff, and branched plant up to 1 meter highStems are covered with soft gray hair or napLower leaves are linear, alternate with toothed marginsLavender-white thistle-like flowers have papery spineless bractsThe grayish seeds are 1-2 mm with bristles at one
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PPRL 2010
Centauria solstitialis (yellowstar thistle, Barnaby’s thistle)
Annual herbaceous weed, branching from the base up to 30 cm tall Winged ascending branches with cottony hair covered, basal, lobed leavesYellow disc flowers tipped with characteristic stiff yellow spines 1 to 2 cm) long
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PPRL 2010
Aspartic and glutamic acidsSesquiterpene lactones, solstitialin A 13-acetate and cynaropicrinDopaminergic neurotoxin, 2,3 dihydro-3, 5 dihydroxy-6-methyl-4 (H) pyran-4-1
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PPRL 2010
Weeks to months of exposureGreen yellow star thistle equal to 86 to 200 percent of their body weight before clinical signs develop
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PPRL 2010
Chewing Disease
Dysfunction of facial, mouth, and throat muscles (chewing disease)Facial paralysis that causes “smiling”, tongue lolling, protruding tongue, and head tossingDepression, loss of interest in food, dehydration and malnutrition, difficult breathing, incoordination, muscle tremors
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PPRL 2010
Negropallidal encephalomalaciaNecrosis of the substancia nigra and globus pallidus (negropallidal encephalomalacia)As there is no treatment and the disease is irreversible, it is best to avoid exposure.