Transcript Plant Toxicology

Plant Toxicology
BSCI493
February, 2008
What is a poison?
• Paracelsus (1493 – 1541) “…the only
difference between a medicine and a
poison was the dose.”
• All substances have a potential toxicity.
• A substance that has a harmful effect on a
living organism. Is poison ivy a poisonous
plant?
Dose-response relationship
• Lethal dose and LD50: 50% of animals exposed
to a specific substance died as a result. Could
be oral, dermal, intravenous or inhaled dose.
Also, several animal systems can be used (rat,
mouse, dog, etc). LD50 is expressed as
mg of chemical / kg of body weight
• Acute toxicity – substance can do systemic
damage after one time exposure to large dose
and effects are almost immediately apparent.
• Chronic toxicity – damage caused by repeat
exposure or bio-accumulation
Indicators of toxic response
• Death
• Changes in
– Body temperature
– Pulse
– Respiratory rate
• Onset of nausea or vomiting
• Marker metabolites can also be present in
tissues or fluids.
How do plant toxins do damage?
• Bind to receptors (e.g. phytohormones
altering synthesis patterns)
• Bind to receptors (e.g. B-adrenoreceptors
changing blood pressure)
• Interrupt metabolism of carbohydrates,
proteins, lipids
• Affect specific organs (e.g. oxylates and
the kidneys, aconitite and the heart)
• Mimic neurotransmitters like serotonin
Absorption and Route of Exposure
• Inhaled through the lungs – mostly limited
to allergic responses; sometimes inhaling
essential oils
• Skin – not often, but can be affected by
suppositories and cosmetics. Mucus
membranes act like an internal skin.
Shedding of mucus membranes – phlem.
• Oral ingestion – teas, tablets/capsules,
tinctures, raw herb
Excretion
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Main route: urine and kidneys
Lungs
GI tract
Sweat
Bile gets recycled (digitalis)
Liver has detoxification enzymes
Metabolism
• Enzymatic systems that are common to most
animals
• Induced – caffeine stimulates adrenaline
(epinephrine) production and turns on MAO,
which breaks down neurotransmitters stimulated
by the adrenaline
• Inhibited – myristicin (from nutmeg) mildly
inhibits MAO: neurotransmitters build up, and
mild psychotropic intoxification occurs
Factors affecting poisoning
• Solubility of toxin in biological medium
(you!)
• Personal state of health – immune health,
nutritional state, stress levels
• Age – elderly and younger (enzymatic
metabolism not fully formed)
• Genetics – is it an adaptation?
Additional concerns
• Contaminants – mycotoxins
• Adulterants
• Compound vs. single constituent
Structural toxicology
• What functional groups on the molecule are
likely to produce reactive metabolites?
• Liver toxicity – acetaminophen reactive
metabolite
• Pharmacogenetic variability in enzymes that
encounter and alter drug compounds
• Idiocyncratic response – small %, but problem if
drug widely used
• In vitro testing doesn’t always catch problem –
requires in vivo and multiple dosing to induce
cytochrome P450’s