pyrrolizidine alkaloid containing plants · pdf filepyrrolizidine alkaloid containing plants...
TRANSCRIPT
![Page 1: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/1.jpg)
PPRL 2010
Bryan StegelmeierADVS 586
February 9, 2010
Pyrrolizidine Alkaloid Containing Plants
April 2009
![Page 2: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/2.jpg)
PPRL 2010April 2009
![Page 3: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/3.jpg)
PPRL 2010
Pyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects, animals and humans.
April 2009
![Page 4: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/4.jpg)
PPRL 2010
OutlinePlantsToxinMetabolismPoisoningSusceptibilityClinical signsLesionsDiagnosisCurrent Research
April 2009
![Page 5: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/5.jpg)
PPRL 2010
PA Global Problem>6000 plants contain PA’s
Most common poisonous plant affecting livestock, wildlife, and humans
Invasive noxious weeds
Contaminated feed, food and herbal preparations
Wide range of susceptibility
April 2009
![Page 6: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/6.jpg)
PPRL 2010
Plants Containing Pyrrolizidine AlkaloidsCompositae Senecio (1200 species) S. jacobaea (tansy ragwort) S. vulgaris (common groundsel) S. longilobus (threadleaf groundsel) S. riddellii (Riddell groundsel)
Fabaceae (Liguminosae) Crotalaria (600 species) C. sagittalis (rattlebox) C. spectabilis (showy crotalaria) C. retusa (wedge-leaf rattlebox) C. pallida (smooth crotalaria) C. juncea (sun hemp)
Boraginacea Amsinckia intermedia (tarweed) Borago officinalis (borage) Cynoglossum officinale (hound’s tongue) Echium plantagineum (echium) Echium vulgare (vipers bugloss) Heliotropiu europaeum (heliotrope) Symphytum officinale (comfrey)
April 2009
![Page 7: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/7.jpg)
PPRL 2010
CompositaeSenecio (1200 species) S. jacobaea (tansy ragwort) S. vulgaris (common groundsel) S. longilobus (threadleaf groundsel) S. riddellii (Riddell groundsel)
April 2009
![Page 8: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/8.jpg)
PPRL 2010
Senecio jacobea
April 2009
![Page 9: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/9.jpg)
PPRL 2010
Senecio riddellii
.
April 2009
![Page 10: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/10.jpg)
PPRL 2010
Senecio longilobus
April 2009
![Page 11: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/11.jpg)
PPRL 2010April 2009
![Page 12: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/12.jpg)
PPRL 2010April 2009
![Page 13: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/13.jpg)
PPRL 2010
Fabaceae
Crotalaria (600 species)C. sagittalis (rattlebox)C. spectabilis (showy crotalaria)C. retusa (wedge-leaf rattlebox)C. pallida (smooth crotalaria)C. juncea (sun hemp)
April 2009
![Page 14: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/14.jpg)
PPRL 2010April 2009
![Page 15: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/15.jpg)
PPRL 2010
Boraginacea Amsinckia intermedia (tarweed) Borago officinalis (borage) Cynoglossum officinale (hound’s tongue) Echium plantagineum (Patterson’s curse) Echium vulgare (viper’s bugloss) Heliotropium europaeum (heliotrope) Symphytum officinale (comfrey)
April 2009
![Page 16: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/16.jpg)
PPRL 2010
Cynoglossum officinale
April 2009
![Page 17: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/17.jpg)
PPRL 2010April 2009
![Page 18: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/18.jpg)
PPRL 2010April 2009
Amsinckia intermedia (tarweed)
![Page 19: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/19.jpg)
PPRL 2010
Crop vs Weed
Echium plantagineum Patternson’s Curse Salvation Jane
April 2009
![Page 20: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/20.jpg)
PPRL 2010April 2009
Echium vulgare (viper’s bugloss)
![Page 21: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/21.jpg)
PPRL 2010April 2009
![Page 22: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/22.jpg)
PPRL 2010April 2009
![Page 23: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/23.jpg)
PPRL 2010April 2009
![Page 24: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/24.jpg)
PPRL 2010
Pyrrolizidine alkaloids: Chemistry
April 2009
![Page 25: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/25.jpg)
PPRL 2010
Pyrrolizidine Alkaloids: Metabolism
April 2009
![Page 26: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/26.jpg)
PPRL 2010
N
OO
CH2
O
O
HO CH2OH
RiddelliineN
N
OO
CH2
O
O
HO CH2OH
N
OO
CH2
O
O
HO CH2OH
CH2OHHO
O
O
CH2
O
OHOH OH
OHEsteraseHydrolysis
N-Oxidation
Necine base and Necic Acid
Riddelliine N-oxide
+
-
Necine
Necic Acid
1
Dehydrogenation (Oxidation)
Pyrrolic Riddelliine
2
3
4
Riddelliine-Glutathionine
RiddelliineRiddelliine-
N
OS
Protein
DNA
N
OHOH
Pyrrolic DNA orProtein Adducts
Pyrrolic Necic Acid
Pyrrole Recyclingw ith continued proteinand DNA damage
Formation of Pyrrole ProteinDNA Adducts
Formation of Pyrrole ProteinDNA Adducts
Polymerization
Reaction w ith soluble nucleophiles
Dehydrogenation (Oxidation)
5
6
7
8
April 2009
![Page 27: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/27.jpg)
PPRL 2010
Poisoning
Accidental
Palatability
Feed Contamination
Herbal Supplements
April 2009
![Page 28: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/28.jpg)
PPRL 2010
Feed and Food Contamination
Native and introduced species invade ranges and fields.Though most are not palatable they are eaten in prepared feeds.Animal products?Human poisoning occurs.
April 2009
![Page 29: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/29.jpg)
PPRL 2010
Susceptibility
Age
Species
Sex
Nutritional Status
April 2009
![Page 30: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/30.jpg)
PPRL 2010
Neonatal riddelliine toxicity of pigs5 different age groups of 12 pigs neonates, 3 week old, 6 weeks old, 12 weeks old, 24 weeks old, and year old crossbred pigs dosed with riddelliine at 0.0, 5.0, 10.0 and 20.0 mg/kg for 14 days
April 2009
![Page 31: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/31.jpg)
PPRL 2010April 2009
![Page 32: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/32.jpg)
PPRL 2010
0 6
12 24 Y
3
April 2009
![Page 33: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/33.jpg)
PPRL 2010April 2009
![Page 34: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/34.jpg)
PPRL 2010
Species Susceptibility
April 2009
![Page 35: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/35.jpg)
April 2009
Afghanistan: “Charmak” disease still killing people and livestock16 December 2008 - Over 270 people have been diagnosed with a hepatic veno-occlusive disease (VOD), locally known as “camel belly” or “charmak” disease.
Veno-occlusive Disease
PPRL 2010
![Page 36: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/36.jpg)
PPRL 2010
What about the pyrrole?
April 2009
![Page 37: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/37.jpg)
PPRL 2010
Is exposure changing?
April 2009
![Page 38: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/38.jpg)
April 2009 PPRL 2010
![Page 39: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/39.jpg)
PPRL 2010
Clinical Lesions- Dose Dependent
April 2009
![Page 40: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/40.jpg)
PPRL 2010April 2009
![Page 41: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/41.jpg)
PPRL 2010
Leakage enzymes (AST, ALT, SDH, LDH)Billiary proliferation (ALP, GGT)Cholestasis (Bilirubin, Bile Acids, Dye retention)
April 2009
![Page 42: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/42.jpg)
PPRL 2010
Clinical Signs
LethargyAnorexiaPhotosensitivity and solar dermatitisDiarrheaWeaknessWandering or blindnessBelligerenceAscites
April 2009
![Page 43: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/43.jpg)
PPRL 2010April 2009
![Page 44: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/44.jpg)
PPRL 2010April 2009
![Page 45: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/45.jpg)
PPRL 2010
Hepatic lesions Yellow soft liver Hepatocyte
necrosis, fibrosis, biliary hyperplasia
Generalized icterus Subcutaneous and
visceral edema Species related extra-
hepatic lesions
April 2009
![Page 46: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/46.jpg)
PPRL 2010
Secondary Lesions
Wasting cowHepatic encephalopathyIcteric and hyperbilirubinemiaEdema and dilated lymphaticsGross liver necrosisEdema (colonic and abomasal)Vascular thrombosis and intestinal infarctionPhotosensitivity and dermal necrosis
April 2009
![Page 47: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/47.jpg)
PPRL 2010April 2009
![Page 48: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/48.jpg)
PPRL 2010April 2009
![Page 49: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/49.jpg)
PPRL 2010April 2009
![Page 50: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/50.jpg)
PPRL 2010April 2009
![Page 51: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/51.jpg)
PPRL 2010
Dose Dependent- Histologic Lesions•Portal circulation•Hepatic metabolism•Hepatocyte response•Classical response
•Necrosis•Fibrosis•Biliary hyperplasia
April 2009
![Page 52: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/52.jpg)
PPRL 2010
Acute Toxicity
Chronic Toxicity
April 2009
![Page 53: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/53.jpg)
PPRL 2010
Pyrrole Detection
April 2009
![Page 54: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/54.jpg)
PPRL 2010
ELISA Studies
April 2009
![Page 55: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/55.jpg)
PPRL 2010April 2009
![Page 56: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/56.jpg)
PPRL 2010
Class and alkaloid specific ELISA’s
April 2009
![Page 57: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/57.jpg)
PPRL 2010
Riddelliine conjugate vaccine trial
Three groups of 30 rats were immunized with two riddelliine conjugates and a sham ovalbumin conjugate.three groups of 10 dosed with riddelliine of 5 mg/kg (25% LD50), 15 mg/kg (75% LD50) and 30 mg/kg (150% LD50) for 10 days. Serum was collected and tissues were collected for evaluation..
April 2009
![Page 58: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/58.jpg)
PPRL 2010Control NCrot Conjugate
April 2009
![Page 59: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/59.jpg)
PPRL 2010
Which rat was vaccinated? Real blind study.
April 2009
![Page 60: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/60.jpg)
PPRL 2010
NCrot Conjugate/25 mg/kg Riddelliine/High Titer NCrot Conjugate/25 mg/kg Riddelliine/Low Titer
April 2009
![Page 61: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/61.jpg)
PPRL 2010
Diagnosis
April 2009
![Page 62: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/62.jpg)
April 2009
Current Research Plan Objectives
Objective 1: Develop diagnostic techniques and biomarkers to better identify animals poisoned by pyrrolizidine alkaloids (PA’s) and their subsequent metabolites, and develop techniques to monitor foods and feeds for PA-contamination.Objective 2: Determine pyrrole toxicity and carcinogenicityand compare pyrrole toxicity with that of PA and PA-n-oxides. Characterize the risk to fetuses and neonates that are exposed by maternal PA-ingestion. Sub-Objective 2.1: Determine pyrrole toxicity and carcinogenicity. Sub-Objective 2.2: Characterize transplacental and
transmammary toxicity of various PA’s.
PPRL 2010
![Page 63: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/63.jpg)
April 2009
Immunologic Diagnostics
DNA ConjugatesThymidine Conjugates
Protein Conjugates
Glutathione Conjugates
PPRL 2010
![Page 64: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/64.jpg)
April 2009
Diagnostic Immunochemistry
(ELISA)
PPRL 2010
![Page 65: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/65.jpg)
April 2009 PPRL 2010
Pyrrole kinetics
![Page 66: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/66.jpg)
April 2009 PPRL 2010
![Page 67: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/67.jpg)
April 2009
Objective 2: Determine pyrrole toxicity and carcinogenicity and compare pyrrole toxicity with that of PA and PA-n-oxides. Characterize the risk to fetuses and neonates that are exposed by maternal PA-ingestion.Sub-Objective 2.1: Determine pyrrole toxicity and carcinogenicity.Sub-Objective 2.2: Characterize transplacental and transmammary toxicity of various PA’s.
PPRL 2010
![Page 68: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/68.jpg)
April 2009 PPRL 2010
![Page 69: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/69.jpg)
April 2009
Upregulated or sensitized mice model
P450 upregulation Phenobarbital Spironolactone
Glutathione depletion (BSO)Pilot Study: Groups of 3 sensitized mice dosed with riddelliine for 14 days
PPRL 2010
![Page 70: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/70.jpg)
April 2009
Pilot Study
Phenobarbital and spironolactone increased susceptibilityBSO (L-buthionine (S,R)-sulfoximine) alone or in combination was poorly toleratedHistology studies are underway
PPRL 2010
![Page 71: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/71.jpg)
April 2009 PPRL 2010
![Page 72: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/72.jpg)
April 2009
Heterozygote TRP53 mutated mice model
Carcinogenesis endpointRiddelliine challenge at 0, 5, 15, and 45 mg/kg/day for 14 days. Monitor neoplastic transformation
PPRL 2010
![Page 73: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/73.jpg)
PPRL 2010April 2009
![Page 74: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/74.jpg)
April 2009
Current Direction
Continue synthesizing pyrrole conjugatesFurther define and characterize small animal model (sensitized mouse)Compare free base, n-oxide and pyrrole toxicity in vitro and sensitized mouse modelsComplete characterization of P53 knockout carcinogenicity model
PPRL 2010
![Page 75: Pyrrolizidine Alkaloid Containing Plants · PDF filePyrrolizidine alkaloid containing plants are the most widespread and expensive poisonous plant problem that affects plants, insects,](https://reader031.vdocuments.us/reader031/viewer/2022022502/5aabacaf7f8b9ac55c8c2aca/html5/thumbnails/75.jpg)
Reading Assignment:
Cheeke: Natural Toxicants in Feeds, Forages and Poisonous Plants
Pyrrolizidine Alkaloids 338-352
PPRL 2010April 2009