Plant Toxins Flashcards
1
Q
Define Toxin
A
poisonous substance produced by cells or living organisms
2
Q
‘Toxin’ origin
A
- from the greek ‘toxikon’
- meaning ‘poison for use on arrows’
3
Q
Dosage of Toxins
A
- is often the critical difference between medical or recreational effect vs. toxic effect
- effect can range from an adverse physiological reaction to death
4
Q
History of Poisons
A
- Assyrians wrote of plant poisons over 3000 years ago
- greeks attribute discovery of poisonous plants to Hecate
- Roman herbalists were often accomplices to murder
- Arab cultures in 9th century perfect the art of poisoning
5
Q
Who is Hecate
A
greek goddess of sorcery
6
Q
How were poisoning with herbs popular with Roman herbalists
A
- most poisonous herbs were readily available for other uses
- murder from a distance
- calculate dosage so that victim was killed slowly over time
7
Q
Death of Cleopatra
A
- Queen Pharaoh of Egypt 51 to 30 BC
- has son with Julius Caesar and Rome becomes involved with the ruling of Egypt
- following Caesar’s death, she forms an alliance with Mark Antony
- eventually overthrown by Octavian
- she first experiments with different plant extracts on slaves
8
Q
what plant extracts does cleopatra experiment with?
A
- henbane and belladona work quickly but are painful
- strychnine works quickly, but leaves the face distorted
- supposedly, she decides on Asp’s venom
9
Q
Historic ways to avoid being poisoned
A
- avoid eating foods that smell or taste ‘wrong’
- use of special goblets (“unicorn horn”,embedded with amethyst or emeralds)
- use special stones to neutralize poison (toadstones, bezoar stones)
10
Q
Historic Antidotes and Cures
A
- most cures instruct victim to induce vomiting
- use antidotes called Theriaca (remedies for venomous bites)
11
Q
Nero
A
- poisons his stepbrother to gain the throne
- worries he will be poisoned as well
- has his physician, Andromachus, make a theriac containing 78 ingredients
- contains opium, lizard, snake flesh
- antidote becomes popular through rome
12
Q
Mithridates Eupator
A
- 120-66 BC
- king of Pontus (on the black sea)
- is extremely paranoid of being poisoned
- takes small doses of the herbal poison/antidote to make himself immune
- romans attack in 66 BC
- he tries to poison himself, but has become too tolerant
- has a slave stab him to death
- Mithridatism means acquired tolerance to poisons
13
Q
Toxic Alkaloids
A
- piperdines (coniine)
- tropane alkaloids (anticholinergics from hallucinogenic plants)
- pyrrolidines (nicotine)
- quinolizidines (lupinine)
14
Q
Examples of Terpenoid alkaloids
A
- cyclopamine (veratrum californicum)
- aconitine (aconitum species)
15
Q
Examples of Indoles
A
- ergot (claviceps pupurea)
- strychnine
16
Q
Examples of Complex alkaloids
A
- tubocuraine (Chondrodendron tomentosum)
- physostigine (physostigms venonosum)
17
Q
Cyclopamine
A
- is a teratogen
- grazing animals who ingest it have offspring with severe defects
- inhibits normal protein patterning in developing organisms
18
Q
What is the compound Cyclopamine named after?
A
named after the mythical cyclops spoken of in Homer’s odyssey
19
Q
Sonic Hedgehog Signaling and Development
A
- normal development involves sonic hegdehog activation of a signaling pathway
- failure of the cerebral hemispheres of the brain to divide (holoprosencephaly)
- affects the same development signaling pathway (without cyclopamine)
- phenotypes can range from mild to severe
20
Q
Aconitum napellus
A
- aconitine or aconite
- known as monkshood, friar’s cap, auld wife’s huid, brute killer, leopard killer, wolf’s bane
- has hooded flowers in shades of greenish and purplish hues
21
Q
Mechanism of Aconitum napellus
A
- reduces ion selectivity of sodium channels
- increases uptake of sodium
- produces cardiac arrhythmias (depression of respiration, death)
22
Q
Strychnine (production and historic uses)
A
- strychnos nux-vomica
- tree produces strychnine in fleshy orange-red berries
- native to tropical southeast asia and Australia
- used by Indigenous people to make poison arrows for hunting
- also used in rat poison
23
Q
Physiological effects of Strychnine
A
- has stimulant effects
- increases respiration and circulation
- once used as an antidote in cases of poisoning by alcohol or barbs
- minimal therapeutic index limited clinical use
24
Q
Low dose vs. High dose in Strychnine
A
- low dose = CNS stimulant
- high dose = acts as a convulsant, seizure activity in the brain, contract all muscle, face contorts, breathing is cut off, death follows
25
Q
How is Strychnine a complex structure?
A
- is a monoterpene alkaloid
- amino acid (tryptophan)
- monoterpene isoprene units
26
Q
Strychnine one of three alkaloids used by athletes:
A
- 1800-1900s
- used to improve performance
- two others were cocaine and amphetamine
27
Q
Thomas Hicks
A
- used a mixture of strychnine and brandy to win the marathon in 1904 olympics
- collapsed at the end of race, but survived
28
Q
Arrow Toxins
A
- alkaloids and cardiac glycosides
- aids to hunting
- arrow toxins contain water soluble mixture of cardiac poison and muscle paralyzing poison
29
Q
Arrow toxins used in south america (example)
A
- muscle paralyzers
- antidotes exist and artificial respiration can be used to revive those affected
- example: curare and phytostigmine
30
Q
Arrow toxins used in Africa and Asia
A
- cardiac poisons
- no antidotes or treatments for cardiac poisons
- examples: ouabain and strophanthidin
31
Q
Curare used in South America blowpipe dart poison
A
- 16th century explorers report that indigenous people in brazil, peru, ecuador and columbia use arrows tipped with curari or woorali
- crude dried plant extract
- usually mixed with various strychnos species
32
Q
Potency of Curare
A
- preparation involves making an aqueous extract of bark from plant vines
- concentrate it into a tar-like mass
- classified as ‘one tree curare’ if a wounded monkey could one leap before dying
- ‘three tree curare’ could be used to capture animals alive
33
Q
Charles Waterton (1820s)
A
- revived a donkey dead from curare poisoning by artificial ventilation using a bellows
- curare causes death by asphyxiation
34
Q
Claude Bernard (1850s)
A
- french physiologist
- shows that curare preparations block transmission of nerve impulses in frogs
- death is caused because the chest and abdominal muscles become paralyzed
35
Q
Why is Curare so complex?
A
- is a complex mix of alkaloids
- structure is plant species dependent
- major components are Curarines and Strychnine derivatives
36
Q
Richard Gill (1920s)
A
- brings back 30 pounds of curare and lobbies drug companies
- eventually Squibb and Burroughs Welcome experiment with curare as a muscle relaxant during anasthesia
- experimental animals died until it was realized that artificial ventilation was necessary during the surgery
37
Q
Mechanism of Actions of Curare
A
- curare is a competitive antagonist at NAChR
- in the neuromuscular junction, this inhibits the ability for acetylcholine to elicit muscle contraction, resulting in paralysis
38
Q
Physosotigmine
A
- physostigms venenosum
- known as Eserine
- produced from the Calabar bean
- interacts with and inhibits acetylcholinesterase
- results in more ACh in the synapses
39
Q
Functions of Physostigmine
A
- has been used to treat myasthenia gravis
- recently used to treat Alzheimer’s disease
40
Q
Acetylcholinesterase and Physostigmine
A
- acetylcholinesterase quickly removes acetylcholine from the synapse
- physostigmine inhibits acetylcholinesterase, resulting in more acetylcholine in the synapse
41
Q
Historical use of Physostigmine (Britain)
A
- calaber bean was used in ‘trials by ordeal’
- 1840 British Army medical officer observes the African natives
- used to reveal witches
42
Q
Ouabain
A
- African Arrow poison
- Cardiac glycosides
- used on arrows by hunters in Africa
- described by Victorian explorer David Livingstone : lowers heart rate and regulates arrythmias, high doses can kill
- not absorbed be GI tract so it is safe to eat poisoned animals
43
Q
Ouabain Mechanism of Action
A
- inhibits the sodium/potassium ATPase that maintains ion gradients in heart muscle cells
44
Q
Toxic Phenolics
A
- Lignans (podophyllotoxin)
- coumarins (methoxypsoralen, aflatoxins)
- tannins
- other phenolics (urushiol)
45
Q
Aflatoxin (aspergillus sp.)
A
- fungus, difuranocoumarins
- contaminate corn, cereals, sorghum, peanuts
46
Q
How are aflatoxins carcinogenic?
A
- carcinogenic to humans and animals
- toxin intercalates and alkylates DNA, inducing mutation
- linked to hepatocellular carcinoma
47
Q
Case of Aflatoxicosis
A
- 200 villages in Western India
- poor people ate badly molded corm
- high mortality rate due to massive GI bleeding
- possible use of aflatoxin as a biological weapon
48
Q
Tannins Uses
A
- astringent phenols
- bind proteins and precipitates them out of solution
- used in medicines to draw irritants out of the skin
- used to transform animal hides into leather
- tannin action can be oncogenic or anti-oncogenic
49
Q
What kind of taste do tannins produce and why?
A
produce bitter tasting tannins as defense against predation
50
Q
Human consumption of tannins
A
- tea, coffee, wine
- frequent drinking of strong tea linked with esophageal cancer
- reduce risk by taking tea with milk (casein fixed the tannin, preventing its action on mucous membranes of mouth)
51
Q
Toxic Amino Acids and Proteins
A
- coprine
- amatoxin and phallotoxin
- lectins (ex. ricin)
52
Q
Coprinus atramentarius
A
- toxis amino acid
- inky cap mushrooms (edible)
- produces coprine (aa that interferes with body’s alcohol metabolism)
- inhibits acetaldehyde dehydrogenase (mitochondrial enzyme)
53
Q
Toxic Mushrooms
A
- amanita phallosides (death cap mushroom or Angel of death)
- Amanita vivrosa (destroying angel)
- both contain deadly amatoxins and phallotoxins
54
Q
Symptoms of Amanita phallosides and Amanita vivrosa?
A
- 12-24 hours after ingestion: violent and prolonged abdominal pains, vomiting, diarrhea, respiratory distress, symptoms subside
- 4-11 days after ingestion: liver damage and failure, coma and death
55
Q
Amatoxin
A
- selectively absorbed by hepatocytes
- specifically inhibit RNA polymerase II
- transcription inhibited
- used as a research tool to study transcriptional regulation in animal and plant cells
56
Q
Phallotoxin
A
- binds protein on hepatocyte plasma membrane
- results in membrane leakiness that comprises cellular function (efflux of K and Ca)
- phalloidin binds to actin subunits (used as a research tool to study cytoskeletal function)
57
Q
Lectins
A
- highly toxic proteins of non-immune origin
- has two sugar binding sites
- cause agglutination and precipitation of sugar molecule complexes
58
Q
Ricinus communis
A
- castor bean plant
- acts as a ribosome inactivating protein
- is the most toxic naturally occuring compound
59
Q
Ricin Poisoning
A
- ingestion of 3 seeds is fatal to most adults
- inhibition of protein synthesis in intestinal wall
- causes clumping of red blood cell
60
Q
Symptoms of Ricin Poisoning
A
- nausea, vomiting, burning sensation in throat and mouth
- followed by hemorrhaging in the GI tract, liver and kidneys
- kidney failure and death
61
Q
Ricin Mechanism of Action
A
- heterodimer (2 different polypeptides, RTA and RTB)
- RTA and RTB linked by disulphide bridge
- RTA, enzyme
- RTA, lectin
62
Q
RTB
A
- sugar-binding lectin
- binds to target cell surfaces
- interacts with any galactose or N-acetylgalatosamine terminating olgosaccharide
- mammalian cells have many such surface binding sites
63
Q
RTA
A
- N-glycosidase, prevents mRNA translation
- inactivates 60S subunits of eukaryotic ribosomes
- irreversibly hydrolyzes a specific adenine-ribose bone of the 23S rRNA that is part of the 60S ribosomal subunit
- one RTA molecule can remove adenines from 1500- 2000 ribosomes per minute
64
Q
Ricin mechanism as a cell toxin
A
- requires both parts of the ricin molecule
- entry via endocytosis
- RTA enters cytoplasm and accesses its rRNA substrate
65
Q
Two functions of RTB in the Ricin mechanism as a cell toxin
A
- binds to specific cell surfaces
- aids entry of ricin (RTA-RTB) into target cell
66
Q
Georgi Markov
A
- was a successful playwright and novelist
- was stabbed in his right thigh by an umbrella and was rushed to the hospital the next day
- autopsy showed that death was due to blood poisoning
- discovered a metallic bead located just under the skin
