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PPRL 2010
Lecture Outline
Introduction Aristolochia spp. Larkspur
DefinitionsMechanism of ToxicitySpecific Tissue Toxicities
PPRL 2010
Aristolochia fanchi substituted for Stephania tetrandra Chinese herb ‘Mu Tong’
Weight loss herbal product
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)
PPRL 2010
Knowing it is poisonous is not enough.
TreatmentSelect resistant animalsMedical applications
PPRL 2010
Physiologic Response to Insult
Molecular Response No change Molecular
damage Repairable or
Permanent damage
PPRL 2010
Tissue Responses
No ChangeLoss of functionInflammation Rubor Calor Tumor Dolor Loss of Function
NecrosisHyperplasiaNeoplasia
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
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.
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)
PPRL 2010
Local irritant
Contact dermatitis-urushiols, Urtica spp., Stinging treesStomatitis/Gastritis-tannins, phenolic, astringents, saponinsOxalates: Dumb cane (Dieffenbachia sequine)Proteolytics- bromelain and papain, lectins
PPRL 2010
Receptor mediated:
AchR- Larkspur alkaloidsNicotinic AchR- Lupine, Tobacco, ConineSteroidal receptors-Veratrum ICA pine needles
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
PPRL 2010
Antinutritional:
Indospecine (arginine analog) Indospecine spicataMimosineSelenium toxicity-Anti-trypsin, anti-amylaseThiaminase
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
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
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
PPRL 2010
Nephrotoxic Plants
Oxalate containing plants- Halogeton and greasewoodOak and other plants causing nephrosis
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Plants with Reproductive Toxins
Pinus ponderosa and broomweedTeratogens such as Veratrum, Lupine etc
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
PPRL 2010
Plants that are Cardiotoxic or Myotoxic
White snakeroot and rayless golden rodOleander and milkweedsThermopsis
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)