Chapter 27

Toxic Effects of Plants, Fungi, and Algae

Toxic Effect by Organ

Skin

a. Contact DermatitisMany plants common to temperature regions worldwide contain compounds that produce irritation on contact with the intact plant.

Ranunculus (Buttercup)- contains ranunculin, which releases toxic protoanemonin (also present in

Anemone – another genus of Buttercup)- Protoanemonin is readily converted to Anemonin, which has marked irritant

properties.- Ingestion of Protoanemonin may result in severe irritation of the GIT.

Dieffenbachia plant

- Contact of the tongue to the juice may result in pain and rapid development of edema and inflammation, which may take days or weeks to subside.

- Toxicity is due to:1. Release of histamine or serotonin-like chemical2. Release of Raphides

Urtica (Nettles)

- Contact with the trichomes causes pain and erythema after penetration of the skin.

- Urtica urens and Urtica dioica – the trichomes covering the leaves and stems consist of fine tubes with bulbs at the end that break off in skin and release fluid containing

o Histamineo Acetylcholineo Serotonin

b. Allergic Dermatitis

Philodendron scandens (family Araceae, Arum family)- Common houseplant- Active Ingredient : Resorcinols

Rhus radicans (anacardiaceae, cashew family)- Native to North America

- Poison ivy, Poison oak(Rhus diversiloba), Poison sumac(Rhus vernix).- Allergic component: mixture of catechols called urushiol

** repeated exposure to sap of mango fruit may also develop allergic dermatitis because of the oleoresins that cross-react with allergens of poison ivy.

Daffodils, hyacinths, and tulips

- when contact with the sap may develop allergic dermatitis- rashes are due to alkaloids such as masonin, lycorin) or to needle-like crystals of

calcium oxalate- tupalin-A causes “tulip fingers”

Prohevein

- major allergen in natural rubber latex from the rubber tree (Hevera brasiliensis)- a chitin-binding polypeptide- individuals sensitive to latex rubber may be sensitized to fruits containing

chitinase : banana, kiwi, tomato,a nd avocado

Family Asteraceae

- Mugwort, Artemisia vulgaris, Europe, Ambrosia artemisifolia - Causes summer rhinitis- Profilin – 14-kDa protein , a cross-reacrtive allergen

c. PhotosensitivityPoisoning of livestock from St. John’s Wort (Hypericum perforatum)

- Results in development of edematous lesions of the skin (areas not covered with hair e.g ears, nose and eyes)

- Hypericin, the toxic principle that causes photosensitization - Photosensitization is rare in human-

Respiratory Tract

a. Allergic Rhinitis – rhinitis from inhalation of plant pollens. Also known as “hay fever” or “pollinosis”

b. Cough Reflex - workers who handles Capsicum annum (cayenne pepper) and Capsicum frutescens(chili pepper) have an increased incidence of cough during the day. Major irritants are Capsaicin and dihydrocapsaicin

Gastrointestinal System

a. Direct irritant Effects

California buckthorn (Rhamnus purshiana) – active ingredient is emodin

Tung Nut (Aleurites fordii) - seeds is the most toxic part

Buffalo bean or buffalo pea (Thermopsis rhombifolia)- active substances are quinolizidine alkaloids

Horse chestnus (Aesculus hippocastanum) and Ohio buckeye (Aesculus glabra)- contain glucoside called esculin

Antimitotic effects

a. May apple – contains purgative podophyllotoxin – inhibits mitosis by binding to microtubulesb. Colchicine

Protein Synthesis Inhibition

a. Wisteria floribunda – contain lectin with affinity to N-acetylglucosamineb. Ricinus communis – ricin I and ricin II inhibits protein synthesis. Abrin-a, most potent protein

inhibitor.

Cardiovascular System

a. Cardioactive glycosides- Foxglove – digitalis- Squill – scillaren- Lilly of the valley – convallatoxin- Milkweeds – desglucouzarin- Bay laurel – oleandrin and nerium- Yellow oleander – thevetin A

b. Action on Cardiac Nerves- Protoveratrine, veratramine, and jervine

**Grayanotoxin – produced exclusively by genera of Ericaceae. It shows the opening and closing of sodium channels in nerves.

c. Vasoactive chemicals- Viscotoxins – basic polypeptides that produce hypotension bradycardia,

negative inotropic on heart muscle,and vasoconstriction of the vessels of skin and skeletal muscle.

Liver

a. Hepatocyte Damage- Senecio, Echium, Cynoglossum, Heliotropium, and Symphytum contains

pyrrolizidine alkaloids responsible for hepatic venoocclusice disease.b. Mushroom Toxins

- liver damage by consumption of Amanita phalloides, Galerina, and lepitoa.- Phalloidin – cyclic heptapeptide combines with actin in muscle cells to interfere

with muscle function

c. Mycotoxins - Aflatoxins, ochratoxin A, Zearalenone, Fumonisins are toxins from fungi

d. Lantadene Toxicity- Lantana camara – 1 of the 10 most noxious weeds in the world- Lantadene A –triterpenoid that induces hepatotoxicity

Kidney and Bladder

a. Carcinogenic chemicals - Bracker fern – only higher plant known to cause epithelial and mesenchymal

neoplasms of the bladder in animals.- Ptaquiloside alkylates adenines and guanines of DNA – carcinogenic

Kidney Tubuar Degeneration

a. Xanthium spp (cocklebur, aster family) – induce toxicosis in livestock in pasture where two- and four-leaf seedlings are present.

Active Ingredient: Carboxyatractyloside – cause microvascular hemorrhages in multiple organs.

Clinical signs: Depression and Dyspnea

Pathological findings: Renal Tubular Necrosis and Hepatic Centrilobular Necrosis

b. Cortinarius spp of woodland fungi (in Northern Conifer forests) – poisoning from this plant result acute renal failure that may lead to death.

Renal biopsy – Acute degenerative tubular lesions with inflammatory interstitials fibrosis.

Blood and Bone Marrow

a. Anticoagulants

Sweet Clover (Melilotus alba) – fungal infections caused serious toxicity and death in cattle.

Dicumarol – a fungal metabolite that causes prothrombin deficiency and deaths from hemorrhages.

b. Bone Marrow Genotoxicity

Argemone (Papaveraceae) – produce sanguinarine, a benzophenanthridine alkaloid that intercalates DNA.

* Single low dose has been show to increase chromosomal aberrations in bone marrow cells in mice.

c. Cyanogens

Amygdalin – releases hydrocyanic acid, which combines with ferric ion in methemoglobin or cytochrome oxidase.

- present in kernels of apples, cherries, peaches, bitter almond (Prunus amygdalus)- ingestion of bitter almond seeds causes cyanide poisoning and asphyxiation.

Linamarin – a cyanogenic glucoside found in Cassava (Manihot esculenta, Euphorbiaceae)- may cause konzo, a form of tropical myelopathy with sudden onset of spastic paralysis.

Nervous System

Epileptiform SeizuresWater hemlock (Cicuta maculate) – the fleshy tubers may cause fetal poisoning

characterized by tonic-clonic convulsions.Cicutoxin – the toxic principle that binds to GABA-gated chloride channels.

Contains monoterpenes which in high doses can cause tonic-clonic convulsions: Pennyronal (Hedeoma) Sage (Salvia) Hyssop (Hyssopus)

Excitatory Amino Acids – may act on one or more glutamate receptor subtypes, and excessive stimulation my result in death of the neurons.

Red algae (Digenia simplex) – produces kalinic acid, causing red tide. Green algae (Chondria aranta) – produces domoic acid, a tricarboxylic amino acid that produces

GI distress, headache, hemiparesis, confusion and seizures. Severe memory deficits and sensorimotor neuronopathy are the prolonged effects.

Fly agaric (Amanita muscada) and Pantherina (Panther argaric) – are fungis that contain EAA, ibotenic acid and muscimol that causes CNS depression, ataxia, hysteria hallucinations and sometimes Myoclonic twitching and seizures.

EAAs found in flowerinf plants: Pea family (Leguminosae) – in seeds

Willardiine (Acacia willardina, Acacia lemmoni, Acacia millefolia, Mimosa asperta) – act as agonist in specific glutamate receptors.

Flat pea seeds (Lathyrus slyvestris) – contain 2,4 diaminobutyric acid and beta-N-oxalylamino-L-alanine which cause acute neurologic condition in sheep.

Chuckling pea seeds (Lethyrus sativus) – induces lathyrism.

Motor Neuron Demyelination

Anthracenones – found in seeds of Karwinskia humboldtiana, family Rhamnaceae (buckthorn, coyotillo, tullidora)

Clinical syndromes – ascending flaccid paralysis leading to fatal bulbar paralysis.

Cerebellar Neurons

Swainsonine – an indolizidine alkaloid found in Swainsonia canescens, Spotted locoweed (Atralgus lentiginosus), Locoweed (Oxytropis sericea)

- causes aberrant behavior with hyperexcitability and locomotor difficulty.

Parasympathetic Stimulation

Muscarine – found in mushrooms of genera Inocybe, Citocybe, Omphalatus that causes diarrhea, sweating, salivation and lacrimation.

Parasympathetic Block

Belladonna alkaloids – present in family Solonaceae (the nightshade), are best known for their block of muscarinic receptors presenting tachycardia, dry mouth, dilated pupils, decreased GI motility. Large doses affect CNS – confusion, bizarre behavior, hallucinations, subsequent amnesia.

Scopolamine – Jimsonweed (Datura stramonium) L-Hyoscyamine – Henbane (Hyoscyamus niger), Pituri (Duboisia myoporoides) Atropine – Deadly nightshade (Atropa Belladona) Solanine – Woody Nightshade, Bittersweet (Solanum dulcamara)

Sensory Neuron Block

Capsaicin – found in Capsicum produces burning sensation on VR1 sensory endings, but also desensitizes the transient potential TRPV1 of sensor endings of C-fiber nociceptors to stimuli.

- has therapeutic use in chronic pain.

SKELETAL MUSCLE AND NEUROMUSCULAR JUNCTION

Neuromuscular Junction Block – results from block of postsynaptic Ach (nicotinic) receptors by either an antagonists or agonist causing excessive stimulation followed by prolonged depolarization.

Nicotine – stimulates autonomic ganglia as well as Neuromuscular Junction.Anabasine – present in Tree tobacco produces prolonged depolarization of the junction.Curare – potent neuromuscular blocking agent for skeletal muscle and kills by stopping

respiratory.

Methyllcaconitine – poisoned cattle show muscle tremors, ataxia, and prostration and die from respiratory failure.

Skeletal Muscle Damage

Quinolizidine alkaloids – principally anagyrine and thermopsine found in mature seeds of Thermopis. Present abdominal cramps, nausea, vomiting and headache that lasts for 24 hrs.

BONE AND TISSUE CALCIFICATION

Bone and Soft Tissue

Solanum malacoxylon – contains water-soluble vitamin D-like substance induces calcification of the entire vascular system, esp heart and aorta.

Day-blooming jasmine and Cestrum laevigatum - causes hypercalcemia and extensive soft tissue calcification in animals.

REPRODUCTIVE SYSTEM AND TERATOGENESIS

Abortifacient – swainsonine in legumes Astragalus and Oxytropus.Mimosine – causes incoordinated gait goiter and reproductive disturbances including

infertility and fetal death.Lectin - from bitter melon seeds

Teratogens – birth defects from alkaloids, jervine, 11-deoxyjervibe an 3-O-glucosyl-11-deoxyjervine.