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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?.
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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 • 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