Medical Botany Exam 2

Mycotoxin Gold Rush

1960 - 1975

Many scientists joined the well-funded search for toxigenic agents produced by fungi. Cause a bunch of people died from contaminated peanut butter?

How many mycotoxins identified

400+ compounds now recognized as mycotoxins

“Poisoning by natural means”

Mycotoxin poisoning similar to exposure to pesticides or heavy metal residues, usually accidental exposure.

Severity of mycotoxin poison depends on

Vitamin deficiency, caloric deprivation, alcohol abuse, infectious disease status

Symptoms of disease from mycotoxin depend on:

type of mycotoxin

amount and duration of exposure

age, health, sex of individual

poorly understood factors like genetics, diet, interactions with other toxins

Biggest problem with mycotoxicoses

Heighten vulnerability to microbial diseases, worsen malnutrition effects, interact synergistically with other toxins

All mycotoxins are of fungal origin (microfungi), but

not all toxic compounds produced by fungi are mycotoxins.

Who is at risk of being exposed to mycotoxins, in general

places with poor food handling and storage, places with malnutrition issue, and where there are fewer regulations to protect exposed populations.

Who in US is susceptible to mycotoxin exposure

Hispanic population (consume more corn that rest of population and inner city populations (more likely to live in buildings that harbor high levels of molds)

Control of mycotoxins

Good agricultural practice

sufficient drying of crops after harvest before storage

preventing pre-harvest contamination by increasing host resistance

improved government screening and regulation programs

Mycotoxin ideal environment

Humid, warm, nutrient-rich area

Increasing host resistance:

Plant breeding, genetic engineering (enhance antifungal genes), use of biocontrol agents that target regulatory genes in mycotoxin development

Main mycotoxins that are monitored

Aflatoxins B1, B2, G1, G6

Aflatoxin M1

Ochratoxin A (OTA)

Trichothecenes (DON, HT-2, T-2)

Patulin

Fumonisins

Zearalenone

Citrinin

Aflatoxin M1

Found in dairy, from animals that got aflatoxin B1 from the food they ate

Aflatoxins B1, B2, G1, G6

Peanuts, corn, Brazil nuts, pistachios, pumpkin seeds, cotton seeds, watermelon seeds

Ochratoxin A (OTA)

Cereals, edible animal tissue, raisins, currants, ginger, beans

Trichothecenes (DON, HT-2, T-2)

Corn, wheat barley, oats, rice, rye, sunflower seeds

Fumonisins

Corn and Breakfast cereals

Zearalenone

Corn and corn based foods, wheat, barley, sorghum, rye

Citrinin

Wheat, oat, barley, rice, monascus derivatives, fermented sausage

Ergot Alkaloids

Affect rye, barley, and wheat. Can cause convulsions, nausea.

Salem Witch Trials - women mistaken for witches but they were just infected with this fungi.

Was used to induce contractions for labor.

Patulin

Fruits (apples, pears), non-fermented fruit juices, grains, cheese

Comparable to mycotoxins

Aflatoxins

Isolated after Turkey X Disease (consumption of a mold-contaminated peanut meal)

Four major: B1, B2, G1, G2

B1 is the most potent natural carcinogen known, unfortunately major aflatoxin produced by toxigenic strains,

Aspergillus flavus and Aspergillus parasiticus

How Aflatoxin contaminates via agriculrural products

Natural contamination of agricultural products (cereals, figs, oilseeds, nuts, tobacco, etc)

Contamination in field before harvest

More problems during storage (moist and humidity)

Effect of aflatoxin contamination of grain

Increased farm animal mortality, lowers value of exported grain as animal feeds.

Where is Aflatoxin biggest problem

Countries where population is facing starvation or regulations non-existent or not enforced.

Aflatoxin mechanism of action, effects, affected population

Cytochrome enzymes convert to an epoxide that binds to N7 of guanine. Eventual mutation of G/C to A/T.

Difficult to extrapolate animal results to human cause different enzymes

Can cause liver cancer: prevalent in China, Philippines, Thailand, some African countries. Risk factor: Hepatitis B

Ergot Alkaloids + history, associated drug, effects, structure

Produced by Claviceps, primarily a grass pathogen

Associated with disease since 600 BCE. Common in Europe during Middle Ages. St. Anthony’s Fire - bread from contaminated flour. Eating cereals infected with a toxic cocktail of alkaloids with ergoline ring systems. “Noxious pustile in the ear of grain”. Monks would remove it.

Associated with LSD

Effects - Gangrene: affects muscle, affecting blood supply to extremities. Convulsions (affects CNS), hallucinations

Resembles serotonin

Secale Cereal with Claviceps purpurea. Would do on purpose to produce ergot alkaloids

Corn smut

Produced by fungus, used in some Mexican dishes.

Ergot alkaloids effects on what, mechanisms of action.

Cattle, sheep, pigs, chicken who eat contaminated grains.

Symptoms: gangrene, abortions, convulsions, suppression of lactation, hypersensitivity.

Mechanism of action:

Induce smooth muscle contraction. Midwives used to induce contractions

Ergot Alkaloids History

1943 - Birth of LSD

Developed methergine to control hemorrhaging after childbirth. Continued research led to discovery of LSD. Marketed as Delysid - unsuccessful treatment of schizophrenia

Ergot alkaloids Uses

MK-ULTRA code name. Used after WWII by CIA as truth serum on suspected communists.

Ergotamine - used to treat migraine headaches

Ergot derivatives used in treatment of Parkinsonism.

Fumonisin produced by, economic importance, corn relation

Produced by Fusarium. Alternaria alternata.

Fusarium verticillioides - a corn endophyte that causes seedling blight, stalk and ear rot. Plant can be asymptomatic until smth triggers it. All corn has fungus. but most strains do not produce toxic compound.

Fumonisin Medical Importance

Interference with sphingolipid metabolism in animals, vertebrates. Causes leukoencephalomalacia (hole in head syndrome) in birds and rabbits.

In humans: neural tube defects, linked to esophageal cancer. (Charleston, SC - 7 cases of esophageal cancer from eating lots of corn that was contaminated. City with highest insidence of esophageal cancer among African Americans)

Tricothecenes species, effects.

Over 60 compounds produced by:

Fusarium, Phomopsis, Trichoderma, Myrothecium, Stachybotrys, Trichothecium.

Can cause hemorrhaging, vomiting, dermatitis. Potent inhibitors of eukaryotic translation/protein synthesis. Specifically peptidyl transferase.

Eating mold grain.

Sick building syndrome (Stachybotrys)

Stachybotrys

Black mold, part of Trichothecenes

Found in wet building material, like gypsum board ceiling tiles, wood fiber, A/C vents

Causes Sick-building syndrome

Causes pulmonary bleeding in infants exposed for long time

10th plague visited on Egypt

Hurricanes can increase growth

Nonmacrocyclic and Macrocyclic Tricothecenes

Type A and Type B (Vomitoxin or Food Refusal Factor for animals) both nonmacrocyclic

Trichothecenes, Deoxynivalenol

Most common mycotoxin found in grain, especially barley. Aka vomitoxin or food refusal factor. Causes nausea, vomiting, diarrhea, weight loss and food refusal in farm animals.

Trichothecenes, T-2 and Diacetoxyscirpenol effects

Cytotoxic activity, immunosuppressive effect.

Disease caused by Trichothecenes, T-2 and Diacetoxyscirpenol

Alimentary toxic aleukia - skin inflammation, vomiting, oral cavity necrosis, nose mouth vaginal bleeding, CNS issues.

Cucurbitacins

Antifeedants, steriod compounds. Four ring structure. From Cucurbitaceae - Gourds/squash family

Salivation, stomach cramps, diarrhea, nausea vomiting, even death

Lycorine, Galantamine, raphide oxalates

raphide - crystal structures in cells

Tropane alkaloids

Belladonna extract (atropine) for eye dilation

produced by Nightshade plants

Glycoalkaloids

Potatoes (avoid green parts, sprouts). Increases with light, injury. Produced to protect itself. Sprouts and flowers are very toxic. a-solanine, a-chaconine

Cucurbitaceae

1000 species. Highest portion used for human food. Cucurbitacins. Color change indicates ripening and TOXINS.

Cucubrita, citrillus, trichosanthes, lageneria, luffa, momordica, ecballium

Can make when under stress (drought, too much heat) to protect themselves

Cucurbita (pepo)

Pumpkin, squash, zucchini

Citrillus

Watermelon

Trichosanthes

Snake gourd

Lagenaria

Calabash, Bottle gourd

Luffa

Ridge gourd, luffa

Cucumis (sativus)

Cucumber

Momordica

Bitter melon/gourd

Ecballium

Squirting cucumber

Tetracyclic triterpenes and CE?

Cucurbitacin E sensitized Colorectal cancer cells (CRC) to chemotherapy. Decreases TFAP/Wnt/B-catenin signaling, suggesting that CE can be assist in CRC treatment.

How cancer cells can get drug resistance,

Mutations, efflux pumps,

Below ground structures

Amaryllidaceae: Allium (BULBS)

Araceae: Colocasia (CORMS)

Solanaceae: Solanum (TUBER, enlarged tip of rhizomes)

Discoreaceae: Discorea (TUBER, enlarged tip of rhizomes)

• Convolvulaceae: Ipomea (TUBEROUS ROOTS)

• Euphorbiaceae: Manihot (TUBEROUS ROOTS)

• Apiaceae: Daucus (TAP ROOT)

• Zingiberaceae: Zingiber (RHIZOME)

Bulbs help with asexual reproduction

Amaryllidaceae

Monocots. Allium. Have bulbs. Daffodil bulbs toxic, but onions, garlic (also bulbs) are not.

Toxic for animals tho. Garden lilly, swamp lily.

Araceae

Monocots. Colocasia. Corms are the underground part. Need to cook well because lots of raphides. Taro.

Tubers

enlarged tip of rhizomes. solanaceae and discoreaceae have them

Discoreaceae

Discorea. Yams. Have tubers,

Convolvulaceae

Ipomea. Sweet potatoes. Tuberous roots.

Euphorbiaceae

Manihot. Cassava. Tuberous Roots.

Apiaceae

Daucus. Carrots. Tap root - modified root

Parsley family

Zingiberaceae.

Zingiber. Ginger. Rhizome - modified stem

Lycorine

Found in daffodils, garden lily, swamp lily. Alkaloid. Inhibit ascorbic acid synthesis in seeds, needed for germination. Protein synthesis inhibition. Weakly inhibits acetylcholinesterase (AChE).

But, potential as anti-cancer drug candidate in low doses.

Narcissus daffodils

Amaryllidaceae family. Bulbs. Produces:

Lycorines, Raphides, Galantamine

Raphides

Calcium oxalate crystals. Released from cells when destroyed and cause inflammation.

Galantamine

Drug used for myasthenia, myopathy, and sensory and motor dysfunction. CNS disorders.

approved in the US for the treatment of Alzheimer’s disease and other memory impairments

Allium sativum

garlic

Allium cepa

onion. know how it looks compared to daffodil bulbs!

Borrachero

Devil’s breath. Drug from night shade plants from Bogota, Columbia.

Solanaceae

Potato family (tubers) Trumpet flowers

Brugmansia - angel’s trumpet

Atropia belladonna - deadly nightshade

Datura - jimsonweed

Chili peppers - contain capsaicin

Mandragora - mandrake. consuming can cause auditory hallucinations.

Solanaceae tropane alkaloids

Hysocyamine atropine, scopolamine - holding newspaper structure

Cause dryness, tachycardia, severe hallucinations, confusion, nonsense speech, amnesia, coma, death

Acts as antagonist of acetylcholine receptors?

Mad as a hatter, red as a beet, blind as a bat, full as a flask, hot as a hare, dry as a bone,

Types of acetylcholine receptors

Muscarinic and nicotinic.

Nicotinic ach receptors

In all autonomic ganglia, neuromuscular junctions, some CNS pathways. Allows Na+ influx and depolarization

Muscarinic ach receptors

Produces parasympathetic nerve effects on heart, smooth muscles, and glands. G-protein coupled receptors. In heart, hyperpolarization (K+ channels opened) causes slower heart rate. In digestive tract, depolarization (K+ channels closed and Na+ or Ca2+ let in) causes smooth muscles of digestive system to contract.

Potato scientific name

Solanum tuberosum

a-solanine and a-chaconine

Glycoalkaloids. Synergistic, cell lysis (via membrane disruption), inhibits acetylcholines by hydrolyzing acetyl. gastrointestinal discomfort, rapid/weak pulse and breathing.

a-solanine

can inhibit cholinesterase, disrupt cell membrance, cause birth defects. interacts with mitochondrial membranes, opening K+ channels and increasing membrane potential. Leads to Ca2+ leave mitochondria and enter cytoplasm. Triggers cell damage and apoptosis.

a-chaconine

steroidal. natural toxicant produced in green potatoes, gives bitter taste. produced by tubers in response to stress, giving it insecticidal and fungicidal properties. belongs to chemical family saponins

Are green potatoes dangerous?

Green color indicates production of chlorophyll from light exposure. But increases glycoalkaloid compound solanine.

Scaffold protein manages the biosynthesis of steroidal defense metabolites in plants

Plants toxins affecting the skin/mucous membrane

Raphide oxalates, stinging hairs, chemical irritants, phototoxins, allergens

Raphide Oxalates purpose in plants

pH balance, defense against herbivores, remove excess oxalic acid

Araceae

Arum family. Calcium oxalates crystals (as raphides) in it cause immediate stinging, edema in mouth and throat. Chewing and indigestion issues. Taro

Idioblasts

Cells containing raphides. When damages, crystals penetrate soft tissue, triggering release of histamines from white blood cells. Damage enables other plants chemical to increase pain and inflammation of soft tissue.

Araceae: Taro as food

Dryng, soaking, fermenting, cooking. Needed to reduce calcium oxalates. Elephant ears, taro root.

Polygonaceae

Buckwheat family. Rheum rhabarbarum. Soluble oxalates. Overconsumption can result in crystallization (calcium oxalate) in tissue. Kidney or renal failure.

Araceae family plants

Spathiphyllum (peace lily), Dumb cane, epipremnun, monstera, Colocasia (elephant ears, taro). philodendron

Families containing raphide oxalates

Araceae, polygonaceae, plus 200 more.

Skin structure

Dermis (outer) and epidermis (inner layer).

Neurotransmitters

Agonists and Antagonists

bind to receptor to activate or inhibit its function.

Urticaceae (Urtica)

Has stinging hairs

• Contain histamine, acetylcholine, serotonin

Like loaded hypodermic syringes

Urtica dioica - stinging nettles

Cactaceae Opuntia spp.

Has spines/Barbed glochids. These are technically modified leaves.

Histamine

Inflammatory chemical. Found in plants and animals.

Thorns

Modified branches.

Opuntia

Part of cactaceae family. prickly pear. barbed glochids. cause mechanical dermatitis, made of crystalline cellulose.