pprl 2010. the pathophysiology of poisonous plant intoxication bryan l. stegelmeier january 25, 2010...
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PPRL 2010
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The Pathophysiology of Poisonous Plant Intoxication
Bryan L. StegelmeierJanuary 25, 2010
ADVS 5860
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PPRL 2010
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PPRL 2010
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PPRL 2010
Lecture Outline
Introduction Aristolochia spp. Larkspur
Definitions
Mechanism of Toxicity
Specific Tissue Toxicities
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PPRL 2010
Aristolochia tomentosa
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PPRL 2010
Germany 1950’s
Endemic Uropathy 1980’s
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PPRL 2010
$85 Billion in 2007
Unregulated (Hatch Act)
Unproven efficacy or safety
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PPRL 2010
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PPRL 2010
Aristolochia fanchi substituted for Stephania tetrandra Chinese herb ‘Mu Tong’
Weight loss herbal product
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PPRL 2010
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PPRL 2010
20X Incidence
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PPRL 2010
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PPRL 2010
Recommended it be listed as a known human carcinogen
Dose?Risk of exposure?
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PPRL 2010
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PPRL 2010
Larkspur (Delphinium spp.)
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PPRL 2010
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PPRL 2010
5-10% Death loss
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PPRL 2010
Larkspur Toxins
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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
MLA mechanism of action
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PPRL 2010
Knowing it is poisonous is not enough.
TreatmentSelect resistant animalsMedical applications
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PPRL 2010
Definitions
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PPRL 2010
Physiologic Response to Insult
Molecular Response No change Molecular
damage Repairable or
Permanent damage
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PPRL 2010
Tissue Responses
No Change
Loss of function
Inflammation Rubor Calor Tumor Dolor Loss of Function
Necrosis
Hyperplasia
Neoplasia
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PPRL 2010
Animal Responses
No changeSick- diseaseAttitude AppetiteWeightOrgan or system specific changes (Reproduction, Respiration, Cardiac Function, Hematologic Function, Immune Function, Urinary Function, Gastrointestinal Function, Musculoskeletal Function, Endocrine Function, Neurologic Function, etc)Death
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PPRL 2010
Herd Responses
Stocking Rate
Economic, Emotional, and Physical Factors
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PPRL 2010
Conclusions
There are about 10-20 tissue and animal specific responses and thousands of diseases
Many diseases cause similar responses; few produce specific or pathognomonic lesions.
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PPRL 2010
Direct vs Indirect toxicity
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PPRL 2010
Mechanisms of Action
Mechanical Injury: Various grasses- barley,
foxtails etc- foreign body abscesses, stomatitis, and dermatitis
Cocklebur- gastric obstruction
Turkey mullein (Eremocarpus setigerus) phytobezoars and phytoconcretions
Oxalate crystals (Ca oxalate causing cellular damage like nephrosis)
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PPRL 2010
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PPRL 2010
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PPRL 2010
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PPRL 2010
Local irritant
Contact dermatitis- urushiols, Urtica spp., Stinging trees
Stomatitis/Gastritis- tannins, phenolic, astringents, saponins
Oxalates: Dumb cane (Dieffenbachia sequine)
Proteolytics- bromelain and papain, lectins
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PPRL 2010
Receptor mediated:
AchR- Larkspur alkaloids
Nicotinic AchR- Lupine, Tobacco, Conine
Steroidal receptors- Veratrum
ICA pine needles
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PPRL 2010
Enzyme inhibition:
Glycosidase inhibitors- swainsonine, calystegins, castanospermineTrypsin and amylase inhibitors- soybeans, peas, potatoes, barley, alfalfaDicumarol- vitamin K antagonistMitosis inhibition- S and prophase arrest of PA’s, metaphase arrest of lupinosisCholinesterase inhibitors- Solanum and green potatoes
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PPRL 2010
Antinutritional:
Indospecine (arginine analog) Indospecine spicata
Mimosine
Selenium toxicity-
Anti-trypsin, anti-amylase
Thiaminase
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PPRL 2010
Direct cytotoxity
DNA/protein alkalation/adduct- denaturingInhibit oxidative phosphoralation- Miserotoxin, Cyanogenic glycosides, fluroacetateAlter membrane permeability- digitalisPhysical cellular damage- oxylatesAlter anion or cation metabolism- Ca++Ca chelation- phytic acid and oxalateCalcinogenic glycosidesCu and Zn storageMg metabolism 3-methy-indoleCholestasis- Lantana, saponinsAll other tissue specific direct toxicity
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PPRL 2010
Specific Tissue Toxicity
Neurotoxic Plants 1. Locoweed 2. Yellow star thistle and
knapweed 3. Larkspur 4. Hemlocks 5. Death camas 6. Bracken fern 7. Jimsonweed
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PPRL 2010
Hepatotoxic Plants
Pyrrolizidine alkaloid
containing plants
Tetradymia and
hepatogenic
photosensitization vs
primary photosensitization
caused by St. Johns wort
or spring parsley
Cocklebur
Alsike clover
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PPRL 2010
Nephrotoxic Plants
Oxalate containing plants- Halogeton and greasewood
Oak and other plants causing nephrosis
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PPRL 2010
Plants with Reproductive Toxins
Pinus ponderosa and broomweed
Teratogens such as Veratrum, Lupine etc
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PPRL 2010
Plants that have Gastrointestinal Toxins
Pineapple (bromelain), papaya (papain) proteolytic enyzymesEnzyme inhibitors (typsin and amylase inhibitors) Dieffenbachia sequine-dumb cane, rhubarb, halogeton, greasewood, oak, phenolics, tannins Grasses/Hay (Nitrate/Nitrite, Saponins)Mustards (Brassica, Raphanus, Descurania)Castor BeanSneezeweed (Helenium)Nightshades
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PPRL 2010
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PPRL 2010
Plants that are Cardiotoxic or Myotoxic
White snakeroot and rayless golden rod
Oleander and milkweeds
Thermopsis
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PPRL 2010
Sudden Death without many lesions:
Nitrates (sorghum, various grasses, oats, hay, corn, Kochia, pigweed, Russian thistle, nightshades)
Cyanide (sorghum, larel cherry, arrow grass, chokecherry)
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PPRL 2010
Reading Assignment:
Cheeke “Natural Toxicants in Feeds, Forages, and Poisonous Plants” Part 1, pages 3-51