Ecosystems and Human Health - Chapter 11 pptx

Some fish actually swim in a “cloud” of toxin secreted by skin glands.. Toxic and venomous animals Toxic and venomous marine animals Venoms and toxins are distinguished by the manner in

chapter eleven Animal and plant poisons

“He was a bold man that first ate an oyster”

— Jonathan Swift

Massasauga rattlesnake, eat brown bread

Massasauga rattlesnake, fall down dead

If you catch a caterpillar, give it apple juice

But if you catch a rattlesnake, TURN IT LOOSE!

— Old Ontario skipping rhyme

Introduction

Chemical warfare is widely practiced in the animal and plant kingdoms Just

as microorganisms produce antibiotics that inhibit the growth and reproduc-tion of competing organisms, more complex plants synthesize chemicals that render them unpalatable to potential predators or that are truly toxic, thus selecting for individuals that avoid them or producing aversive reactions that limit consumption to once or twice only Occasionally, however, these plants accidentally enter the food chain of livestock or humans, directly or indirectly, leading to a toxic reaction

Similarly, toxins and venoms are used in the animal kingdom for defense and prey capture Toxins are consumed and operate much like those of plants Toxins can also be secreted by special cells or glands in the skin, so that toxicity may occur simply by taking the intended victim into the mouth Toxic reactions have occurred among students indulging in the fad of “toad-licking.” These toxins tend to be low-molecular-weight peptides with neu-rotoxicity Some fish actually swim in a “cloud” of toxin secreted by skin glands Their toxins are usually steroid glycosides and choline esters A neurotoxin secreted in this way by a species of flounder of the Red Sea is so powerful that a shark attempting to bite it is incapable of closing its jaws and instantly convulses It has been proposed as a shark repellant for

downed fliers and divers These skin toxins also serve as antibacterial agents

to prevent infection, as the slime secreted by the skin of amphibians is an ideal culture medium for bacteria

Venoms are injected in some way and can be employed both for defense and for prey capture Humans and animals sometimes accidentally become the victims of envenomation or intoxication by poisons of animal origin The term toxin is also used to refer to the individual components of venoms Numerous texts have been written on these subjects, and this chapter can

do no more than skim the field and discuss some of the more important, or more interesting, examples Emphasis is placed on agents that have become important to the biological sciences, either as drugs or as research tools

Toxic and venomous animals

Toxic and venomous marine animals

Venoms and toxins are distinguished by the manner in which they are inflicted upon the victim A venom is a substance kept in a special poison gland and administered by a complex injection apparatus or by lacerating spines This type of system can be employed in defense or in prey capture

A toxin is a poison usually ingested as an accidental component of tissues

or organs Toxins likely evolved as a species (rather than an individual) protection Predators with a preference for that prey would be selected out

if the toxin is fatal Conditioned avoidance could occur in survivors The term for poisoning by the muscle tissue of scalefish, as opposed to shellfish,

is ichthyosarcotoxism It includes toxins that are accumulated up the food chain from plankton, as well as toxins that are synthesized by the fish itself

In the former situation, poisoning is usually by a mixture of toxins

Scalefish toxins

Ciguatoxin The condition ciguatera is caused by this toxin, which probably concentrates up the food chain from a photosynthetic dinoflagellate

to reach toxic levels in large marine fish such as grouper, snapper, amberjack, barracuda, and parrot-fish These species are coral reef predators and brows-ers Toxic symptoms are both gastrointestinal (nausea, vomiting, cramps, diarrhea) and neurological (numbness; tingling of lips, throat, and tongue; dizziness; headache) Ciguatoxin is thought to increase membrane perme-ability to sodium and be responsible for the neurological signs and symp-toms Ciguatoxin is very toxic to mice that are the test species for detecting its presence It is a large, colorless, heat-stable lipid molecule, the structure

of which has not been elucidated Other unidentified agents are likely involved in ciguatera poisoning Ciguatera is by far the most common cause

of scale-fish poisoning Any large, warm-water species is a potential source

of the toxin A component of ciguatoxin, maitotoxin, has recently been puri-fied Maitotoxin (MTX) is a water-soluble polyether that is a potent inducer

of an increase in cytosolic free calcium ion [Ca2+]i in a wide variety of organisms, including mammalian cells MTX appears to activate a voltage-independent, nonselective cation channel that may require an extracellular source of Ca2+ for activation MTX has become a useful research tool for studying ion channels (see also http://www.rehablink.com.ciguatera/poi-son.htm) Barracuda sometimes contain a related neurotoxin that is very toxic to cats In some parts of the West Indies, it is customary to feed some

of the meat from a large barracuda to a local cat before humans eat it

Tetrodotoxin. The term comes from Tetraodontidae, meaning four teeth, the name of the genus that produces the toxin This toxin is present in puffer fish, which are called “fugu” in Japan It is a very potent blocker of fast sodium channels, and therefore inhibits nerve conduction in a manner sim-ilar to local anesthetics It causes parethesias, paralysis, anesthesia, and loss

of speech, but consciousness is retained Prognosis is improved if vomiting occurs early after ingestion In Japan there are about 150 cases of poisoning annually, with a 50% mortality Fugu is considered a delicacy in Japan and special chefs are licensed to prepare it The toxin is concentrated in the liver and gonads of the fish Connoisseurs of fugu prefer that just enough toxin remains to cause a slight tingling of the lips when it is consumed In Japan, this custom has spawned a somewhat macabre poetry form: “Last night he and I ate fugu; today I helped carry his coffin.”

Tetrodotoxin is also found in some newts and frogs The blue-ringed octopus, a small octopus that inhabits tidal pools and shallow waters around Australia and other central Indo-Pacific waters, produces a toxin, adminis-tered by a bite, that is believed to be identical to tetrodotoxin The bite of a larger specimen can be fatal in minutes

Tetrodotoxin is of interest as a research tool because of its potent sodium channel blocking activity Its occurrence in such diverse species can be explained by the fact that it is not synthesized by the animal itself, but rather

by certain species of Vibrio bacteria that exist in a symbiotic relationship with the host

Scombroid poisoning. The name scombroid comes from Scombridae, referring to dark-muscled fish such as tuna and mackerel This poisoning results from eating fish rich in histidine Improper refrigeration results in the conversion of histidine to histamine by surface bacteria The signs and symptoms resemble a histamine reaction They may onset in minutes to hours and include dizziness, headache, diarrhea, facial flushing, tachycardia, pruritis, and wheezing Fish contaminated in this way are often described

as having a spicy or peppery taste Levels of histamine in contaminated fish may exceed 100 mg/100 g The FDA has set 50 mg/100 g as the hazard level Histamine is not destroyed by cooking There is some evidence that another product of decomposition, saurine, may contribute to the symptomatology

Icthyotoxin. Many species of fish, including freshwater varieties, sometimes contain a toxin in the gonads that can cause severe gastrointes-tinal symptoms

Shellfish toxins

There is some evidence that there has been a dramatic increase in toxic algal blooms, the so-called red tides The first confirmed outbreak of diarrhoretic shellfish poisoning in North America occurred in 1990 and it was traced to dinoflagellates in Canadian waters Brown pelicans eating anchovies off California were dying of domoic acid poisoning in 1991; saxitoxin has been found in Alaska crabs; and in 1987–1988, shellfishing off North Carolina was shut down because of a red tide of a dinoflagellate that produces a neuro-toxin, brevitoxin

Saxitoxin. The cause of paralytic shellfish poisoning, this toxin is pro-duced by dinoflagellates (single-celled animals that are the cause of red tides) and it concentrates in bivalves such as oysters, clams, and mussels The mechanism and symptomatology are the same as for tetrodotoxin The min-imum lethal dose is about 8 µg/kg for each “Never eat oysters in a month without an R” is an old adage that remains good advice in the Northern Hemisphere as dinoflagellates bloom in the summer months

Domoic acid In 1987, there was an outbreak of mussel poisoning in Canada caused by mussels from the waters around Prince Edward Island The toxin was domoic acid, which concentrates from algae called chondria

It is also found in a diatom and is rare in North Atlantic waters, being more common in Japan The toxin was identified by the Canadian National Research Council Atlantic Laboratory There were three fatalities in elderly nursing home residents in Quebec, and over 100 individuals were affected Several have been left with short-term memory deficits, a condition called

amnesic shellfish poisoning It has been suggested that marine pollution might have changed the environment to favor the growth of the offending diatom Domoic acid binds to a specific subset of glutamic acid receptors, known as kainate receptors, in the brain

Okadaic acid Also produced by a dinoflagellate, okadaic acid is responsible for a condition known as diarrhoretic shellfish poisoning Okadaic acid is a selective inhibitor of phosphatases 1 and 2A with interference to protein activation/inactivation It can induce contraction of smooth muscle and cardiac muscle Experimentally, it is a tumor promoter but, unlike phor-bol esters, it does not activate protein kinase C

Direct toxicity from dinoflagellates

The dinoflagellates that cause red tides are pigmented, plant-like organisms

In addition to being toxic to a variety of marine life, they can be carried into

the atmosphere in aerosols resulting from wave action They can cause respiratory irritation in people and animals coming in contact with the aerosol; and in individuals with preexisting respiratory problems such as emphysema and asthma, the reaction can be quite serious

Over the past decade, a genus of dinoflagellates called Pfiesteria has been responsible for numerous fish kills in North American estuaries, killing an estimated one billion fish in the Albemarle-Pamlico estuarine system and over 50,000 in Chesapeake Bay P piscicida and P shumwayae have a strong attraction for live fish and produce complex toxins that affect neural function and can cause numerous other lesions Fish behave erratically and have skin lesions described as “punched out.” Neurotoxic aerosols can cause central nervous system damage in people, affecting memory, cognitive function, and both the autonomic and peripheral nervous systems Contact with contam-inated water can cause skin lesions and a burning sensation The toxin is water soluble, affects calcium metabolism, and attaches to a purinergic recep-tor on immune cells of the brain Commercial fishers, marine biologists, and lab personnel have been severely affected

Stinging fishes

In venomous fish such as the stonefish, lionfish, scorpionfish, and stingray, spines are located ahead of the dorsal fin, on the tail, or around the mouth

A heat-labile protein causes intense pain and cardiac shock Heat above 50°C may afford some relief Stonefish and stingrays are most often stepped upon because they conceal themselves in the sand bottom Fatalities have occurred from envenomation by these fish, generally as a result of cardiovascular shock, with AV block and bradycardia Other symptoms include numbness, inflammation, and edema at the site of injury, severe pain in surrounding tissues, delirium, nausea, vomiting, and sweating Stingray venom is a large, heat-labile protein (molecular weight > 100,000) with neurotoxic as well as cardiotoxic properties There is an antivenin for stonefish venom

Mollusk venoms

Conotoxins These are found in marine cone snails All are strongly basic peptides, highly cross-linked by disulfide bonds Alpha-conotoxins are nondepolarizing, neuromuscular blocking agents like curare and, therefore, cause paralysis They are 13 to 15 amino acid peptides Mu-conotoxins are

22 amino acid peptides that block sodium channels, thus acting like tetro-dotoxin and saxitoxin These sodium channel blocking conopeptides are under investigation for use in treating chronic pain Omega-conotoxins block presynaptic, voltage-dependent calcium channels Recent research has iden-tified a number of subtypes with specificity for various channel subtypes, making them useful research tools Cone snails are univalve gastropods with

a complex envenomation apparatus used for prey capture (see also http://grimwade.biochem.unimelb.edu.au/cone/newlog.html)

Coelenterate toxins

These are found in jellyfish and corals Fire coral produces a protein venom that causes intense local burning when touched It feels like a cigarette burn

Physalis (Portuguese man-o-war, bluebottle, mauve stinger) causes signs and symptoms similar to fire coral Red streaks, called straps, occur where ten-tacles touch skin Allergic reactions can occur, in addition to generalized symptoms such as fever, nausea, and cardiac and respiratory distress Blue-bottles washed up on beaches remain toxic until completely dried out First aid consists of washing the affected area with vinegar, dilute acetic acid, or meat tenderizer (papain), all of which denature the protein Even urine may help to relieve the pain This species is common around the world

The sea wasp (box jellyfish) is the most venomous marine animal known

It inhabits the Indo-Pacific region and accounts for many deaths annually Contact with tentacles causes intense, agonizing pain, coma, and cardiac shock Mortality is 25% and children, the elderly, and heart patients are most vulnerable First aid is denaturation as above; removal of tentacles using forceps, gloves, a knife and fork, or any means to avoid touching the tenta-cles; and cardiopulmonary resuscitation (CPR) Local anaesthetic spray such

as is used for sunburn may be helpful An antivenin is available The Iru-kandji is a tiny, four-tentacled, Indo-Pacific jellyfish that causes similar signs and symptoms, plus massive sympathetic discharge

Echinoderm venoms

Sea urchins and sea anemones, such as the long-spined or black sea urchin and crown-of-thorns sea urchin, possess toxins Injury usually occurs to the feet and lower limbs when a diver or swimmer steps on these bottom-dwellers Spines are driven into the flesh and break off The toxin produces local pain and burning similar to that of the bluebottle It is heat labile so immersing the affected part in water as hot as the person can stand may help Unlike the usual first aid for envenomations, movement and trauma may actually help by breaking up the spines so they can be absorbed more quickly Vinegar or even urine may also help

Sea anemones also produce very potent toxins that act when they are ingested The best characterized of these are the equinatoxins (EqTs I, II, and III) from Actinia equina In rats they cause coronary vasospasm, cardiac arrest, and other cardiorespiratory toxicity Hemolysis also occurs, as does degran-ulation of blood platelets and white cells

For more information on marine venoms and toxins, see http:// www.pmeh.uiowa.edu/fuortes/63260/MARINEAN/index.htm and http://www.merck.com/pubs/mmanual/

Toxic and venomous land animals

Venomous snakes

Many snakes are venomous, but most have rear fangs that are designed to paralyze prey after it has been taken into the oral cavity These are incapable

of inflicting a venomous bite The four genuses of poisonous snakes that are

a danger to humans include the Viperidae, Crotalidae, Elapidae, and Hydrophidae

1 Viperidae These old-world vipers have hollow, needle-like fangs that are set in short, movable maxilla which rotate to bring the fangs into the biting position as the mouth is opened The head is large and triangular

2 Crotalidae These “pit vipers” are similar to the old-world vipers but they also have a deep, infrared-sensitive pit between the eye and the nostril that is used for tracking prey by body heat This genus in-cludes all rattlesnakes, the water moccasin (cottonmouth, etc.), and the copperhead All are found in North America Canada has the Western diamondback and, in Ontario, the Massasauga rattlesnake

3 Elapidae These are distributed worldwide and account for the most poisonous and feared snakes of the tropics and subtropics This group includes the cobras, the boomslang, and many Australian species (taipan, tiger snake, brown snake, etc.) There are two species in the United States, the Eastern (Florida) and Arizona coral snakes The rhyme “red-on-black, friend of Jack; red-on-yellow, kills a fellow” helps to distinguish the coral snake from a harmless look-alike

4 Hydrophidae These are the sea snakes They are restricted to the warmer waters of the Pacific and Indian Oceans Although they are highly venomous, they are not aggressive Most bites occur to com-mercial fishermen because the snakes become trapped in the nets For some years, sporadic discussions have occurred concerning the feasibility of digging a sea-level canal across the Isthmus of Panama

to connect the Atlantic and Pacific Oceans One environmental con-cern that has been raised is that such a canal could introduce the yellow-bellied sea snake to the Gulf of Mexico and the Caribbean Ocean where conditions are favorable for their proliferation

Snake venoms. These are complex mixtures of proteins, many of which are proteolytic enzymes In general, venoms of the Elapidae and the Hydro-phidae tend to be neurotoxic with myonecrosis (breakdown of muscle tissue) occurring at the bite wound, whereas venoms of the vipers and crotalids are generalized coagulants with local anticoagulant activity to spread the venom, causing much local damage (pain, necrosis, bleeding) Neurotoxicity

in less prominent

Signs and symptoms of neurotoxic venoms include progressive paraly-sis, muscle spasm, respiratory distress or failure, muscle ache (myalgia), kidney failure with myoglobinuria (the appearance of myoglobin in the urine), and cardiac failure These symptoms apply to coral snake bites in North America The venom of the Banded Krait contains alpha-bungaro-toxin, which is an irreversible blocker of acetylcholine receptors, and beta-bungarotoxin, which causes a massive release of neurotransmitter vesicles Alpha-bungarotoxin is used as a research tool in biomedical research The

Black Mamba (Dendroaspis polylepis) produces dendrotoxin-I, another K+

channel blocker

Signs and symptoms of viper and crotalid bites (including the Massa-sauga rattlesnake) include immediate, intense burning at the site of enven-omation (like a bee sting), followed by numbness, swelling, shock, and hematuria Necrosis and possibly gangrene at the bite wound may occur later Subcutaneous hemorrhages may be present and severe cases may show signs of neurotoxicity Table 10 lists some of the major components that have been identified in snake venoms The venom of Russell’s viper contains an activator of clotting Factor X and it is used in coagulation research

Phospholipase A2 complexes in rattlesnake venoms are neurotoxic as well as inducing tissue damage Myotoxic components have exhibited mul-tiple mitogenic effects on growing cultured myocytes

Elapidae and Viperadae both possess alpha-neurotoxins that act postsyn-aptically to prevent acetylcholine from binding to its receptor, as well as neurotoxins that affect transmitter release presynaptically Β-neurotoxins have phospholipase A2 activity The mambas and other African snakes have voltage-dependent K+ channel blockers (dendrotoxins), noncompetitive inhibitors of acetylcholine (fasciculins), muscarinic toxins, and L-type Ca2+

channel blockers (caliseptins) All are small proteins containing about 60 amino acids and 3 or 4 sulfides

Component Elapids Hydrophids Vipers Crotalids

Nicotinic blocker

(neuromuscular blockade)

Cholinesterase

(neurotoxic)

Coagulant protease

(increases clotting)

Anticoagulant protease

(decreases clotting locally)

ATP

(shock, hemolysis)

Phosphatase

(shock, hemolysis)

Phospholipase A

(histamine and SRSA release a )

Bradykininogen

(forms bradykinin, causes pain

at site)

Hyaluronidase

(breaks down connective

tissue, spreads venom)

a SRSA = Slow releasing substance of anaphylaxis (leukotrienes).

There are a few venomous lizards, such as the Gila monster, that inhabit the American Southwest They are not generally as dangerous as venomous snakes The venom lacks neurotoxins but contains coagulants and enzymes

as well as serotonin The reaction tends to be more local Lethal doses in animals lead to cardiorespiratory collapse

First aid. Regardless of the type of snake bite, the most important first aid measure is a tension bandage applied to the entire affected limb with the same tension one would use to bandage a sprain Rest and reassurance are important Transportation to a medical center possessing antivenin should occur as soon as possible Modern hospitals should have the antive-nin (or polyvalent antiveantive-nin) appropriate to their area in stock Forced exer-cise and alcoholic beverages are definitely contraindicated

Venomous arthropods

Members of the order Hymenoptera (bees, wasps, ants) of the class Insecta

and of the class Arachnida (spiders, scorpions) have venoms that contain substances commonly involved in the mammalian pain response The Old World scorpion Leiurus quinquestriatus and the Israeli yellow scorpion (Leiurus q hebraeus) produce charybdotoxin that affects calcium-activated K+

channels, as does the bee venom apamin The Mexican scorpion Centroides noxius produces noxiustoxin, which blocks voltage-dependent K+ channels (see Table 11) Mast cell degranulating peptide in bee venom also blocks these channels

Allergic reactions to any of these insect venoms may occur and may be life-threatening if severe or multiple stings occur The African honeybee is

Histamine Releasers Bradykinin Serotonin

K + Channel Blockers

activated), mast-cell degranulating (MCD) peptide (voltage activated)

Ca 2+ activated R-agitoxin-2 (voltage activated)

(voltage activated)

dangerous not because it is more venomous, but because it is extremely aggressive so that multiple stings are common

Neurotoxins tend to predominate in spider venoms Virtually all spiders are venomous, but only a few have an envenomation apparatus suitable for piercing human skin So-called “widow” spiders (Latrodectus spp.) have a worldwide distribution in temperate and tropical climes The Black Widow, also known as the death spider, as the hourglass spider, and by many other names, inhabits all of Ontario south of Sudbury but is rarely encountered since the demise of the outdoor privy The venom is extremely toxic but very little is injected; thus, fatalities are rare The toxin is complex At least seven

“latrotoxins” have been identified; five are specific for insects, one for crus-taceans and one for vertebrates The latter is alpha-latrotoxin (alpha-LTX)

It is a medium-sized protein now available in pure form (see below) that induces the release of most if not all neurotransmitters It bears similarity to beta-bungarotoxin (found in the Banded Krait) Both cause a massive release

of cholinergic vesicles

Fasciculations and board-like rigidity of the trunk muscles occur rapidly, followed by muscle cramps, pain in the muscles, and respiratory distress The presence of a specific receptor on vertebrate neurones for alpha-LTX has been identified, and this is the likely explanation for the species specificity

of the toxin Recovery from Black Widow spider bite takes about 12 hours The Brown Recluse (Loxosceles spp.), known also as the violin spider, has been working its way north from Mexico and Florida and has reached New York state and probably southern Ontario The bite is painless Local necrosis develops and expands over the next week due to local blood clotting and microthrombosis Occasional deaths have occurred from hemolytic anemia and kidney failure The venom is complex and includes coagulants, enzymes, and a complement inhibitor

The Australian funnel-web and red-backed spiders are claimed to be especially venomous Two funnel-web toxins have been identified: a polyamine (FTX) and omega agitoxin Both block high voltage-dependent

P Ca2+ channels, and they are now used as research tools for this purpose R-agitoxin-2, from the Israeli yellow scorpion, blocks some voltage-activated

K+ channels

Toxic plants and mushrooms

Folk knowledge, passed orally from generation to generation, usually deter-mines what humans can eat and what they cannot eat, and even what parts

of a plant are edible Thus, people make pies from rhubarb stalks but never make salad from the leaves, which are toxic Nor do people eat the bulbs or stalks of the many ornamental flowers and shrubs in their gardens Seldom does one consider the fact that these decisions are toxicologically based The number of plants that are potentially harmful is too voluminous for extensive coverage The subject has formed the basis of many texts The following list