Showing posts with label Toxin. Show all posts
Showing posts with label Toxin. Show all posts


Monocrotaline (MCT) - The lung-killer

  • pneumotoxic macrocyclic pyrrolizidine alkaloid churned out by a number of exciting plants
  • causes a pulmonary vascular syndrome, which essentially means that a bunch of things go wrong with the blood supply to your lungs, including:
    • proliferative pulmonary vasculitis (spreading inflammation of the wall of blood vessels in the lung)
  • used to intentionally produce pulmonary hypertension in animals in order to create an experimental model for investigating the pathophysiology of pulmonary hypertension and the development of pharmacological means of treating it
  • has been hypothesized that it is biotransformed in the liver to a feisty little reactive metabolite that then travels via the blood to the lungs where it starts messing with endothelial cells, altering their function to cause detrimental structural changes in pulmonary blood vessels (particularly the arteries)
  • its selectivity for the lung likely has something to do with the way it is biotransformed by the liver and the manner in which blood circulates through the lungs (vs. any other part of the body)
Tanino Y. [Monocrotaline-induced pulmonary hypertension in animals] Nippon Rinsho. 2001 Jun;59(6):1076-80. Review. Japanese.
Wilson DW et al. Mechanisms and pathology of monocrotaline pulmonary toxicity. Crit Rev Toxicol. 1992;22(5-6):307-25. Review.


Asarone - I wonder what it smells like

  • volatile aromatic ether (structure) continuously brought into this cruel, cruel world by plants of the genus Acorus, particularly Acorus calamus and Acorus gramineus, and Guatteria gaumeri, a member of the Annonaceae family
    • oil of calamus, the essential oil of Acorus calamus, contains a significant amount of asarone, and has been used as a flavouring agent in the food and pharmaceutical industries and a scent in perfumes (these days the asarone is removed first)
  • comes in alpha and beta varieties (cis-trans isomers)
  • allegedly a precursor in the synthesis of 2,4,5-trimethoxyamphetamine (TMA-2), a psychedelic analog of mescaline that is used recreationally and has been sold semi-legally for “research purposes” (hehe)
  • the alpha form has been shown to inhibit a liver enzyme called HMG-CoA reductase, lowering blood cholesterol levels and increasing bile flow
    • HMG-CoA reductase is the rate-limiting enzyme in the mevalonate pathway (by which cholesterol is ultimately produced), such that when it is inhibited, the liver reacts by increasing the amount of low density lipoprotein (along with the "bad" cholesterol it carries) that is excreted via the bile (which you poop out), thus lowering LDL-cholesterol levels
    • statins (y'know, like Lipitor) also lower LDL-cholesterol levels by inhibiting HMG-CoA reductase
  • the beta form is active against a number of annoying bacterial and fungal plant pathogens as well as certain insects
  • both forms cause liver toxicity and cancer in rodents, likely as a result of their bioactivation to a reactive metabolite, putting a wee bit of a damper on drug development
- Hasheminejad G, Caldwell J. Genotoxicity of the alkenylbenzenes alpha- and beta-asarone, myristicin and elimicin as determined by the UDS assay in cultured rat hepatocytes. Food Chem Toxicol. 1994 Mar;32(3):223-31.
- Lee JY, Lee JY, Yun BS, Hwang BK. Antifungal activity of beta-asarone from rhizomes of Acorus gramineus. J Agric Food Chem. 2004 Feb 25;52(4):776-80.
- Rodriguez-Paez L et al. Alpha-asarone inhibits HMG-CoA reductase, lowers serum
LDL-cholesterol levels and reduces biliary CSI in hypercholesterolemic rats.
Phytomedicine. 2003;10(5):397-404


Gossypol - How cotton plants can keep you warm, well-fed, and childless

  • polyphenolic toxin ushered into existence by cotton plants (genus Gossypium)
    • Gossypium sounds funny for some reason (am I alone in thinking this? Must cut back on the late-night blogging)
  • inhibits aldose reductase, an enzyme involved in the polyol pathway by which glucose is converted to sorbitol in the human body
    • the elevation of blood glucose levels in diabetes can lead to the accumulation of sorbitol in cells, which may contribute to diabetic complications including neuropathy, nephropathy, and retinopathy
    • therefore gossypol and other aldose reductase inhibitors could potentially be used to treat diabetic complications
  • has been and continues to be investigated as a possible male oral contraceptive, as it suppresses spermatogenesis (animation!) by some mysterious mechanism
    • lots of research was done in China during the 1970s
    • has not worked out since it has a low therapeutic index and causes things like hypokalemia (low blood potassium levels, results in fatigue and flaccid paralysis), GI upset, and permanent infertility (oops, we irreversibly damaged your testicles!) in some people
  • has been shown to inhibit the proliferation of tumour cells and the replication of HIV, making it a possible candidate for the development of new anticancer/antiviral drugs
  • some food scientists managed to figure out how to genetically engineer cotton plants so that their seeds, which are a friggin' phenomenal source of high-quality protein, contain only miniscule amounts of this toxin, thus rendering cotton plants a potential food crop!
- Kawanishi K, Ueda H, Moriyasu M. Aldose reductase inhibitors from the nature. Curr Med Chem. 2003 Aug;10(15):1353-74. Review.
- Waites GM, Wang C, Griffin PD. Gossypol: reasons for its failure to be accepted as a safe, reversible male antifertility drug. Int J Androl. 1998 Feb;21(1):8-12. Review.


Microbial maladies: Bacterial toxins and the diseases they produce

Mother nature is one twisted old crone. Sure, she's all cute baby animals and pretty flowers and impressively intricate termite colonies, but mark my words, that lady's also got a toxic side. From tiny microbes to towering trees, there exists in this world a multitude of organisms working 'round the clock to synthesize substances capable of killing other living things, including us.

Take bacteria. Within a single genus, Clostridium, you've got:

Clostridium botulinum
Maker of one of the most toxic substances known to exist, botulinum toxin. This badass protein binds to and disrupts the action of nerves that control muscle movement, resulting in paralysis. Death occurs due to asphyxiation, since your diaphragm and all the other muscles that you need to inhale stop working.

Clostridium tetani
Responsible for tetanus (i.e. rusty nail disease), due to its production of tetanospasmin. This downright sinister protein binds to neurons in your brain and spinal cord, preventing the release of inhibitory chemicals that normally keep them from becoming overactive. Hence, your central nervous system goes loco, leading to seizures and tetanic muscle spasms (your muscles contract for long periods of time, during which you are paralyzed) that are so friggin' strong that they can snap your bones. The muscle paralysis occurs first in your face and jaw, producing a characteristic face paralysis (risus sardonicus) and lockjaw.

Clostridium difficile
The scourge of hospitals everywhere, this mofo produces two toxins called enterotoxin and cytotoxin that destroy the cells lining your intestine, resulting in diarrhea and inflammation. Responsible for a very considerable number of hospital deaths and resistant to lots of antibiotics.

Clostridium perfringens
Produces toxins that can cause exciting things like food poisoning and severe infections featuring gas gangrene.

I'm telling you, bacteria are a venerable gold mine of toxic compounds. Some other bacteria and their toxins that are worth noting:

Vibrio cholerae
Causer of cholera, which features intense bouts of diarrhea. So intense, in fact, that if left untreated, you can die within hours of the first squirt since you become so severely dehydrated. The trots are the work of cholera toxin, an enterotoxin that acts on the lining of the small intestine.

Bacillus anthracis
Produces three distinct proteins that together are referred to as anthrax toxin. None of the three cause problems on their own, but when they are brought together they become a neigh-unstoppable force of utter pestilence. Anthrax is interesting because it comes in three different flavours, depending on how the bacteria gets into you. You breathe it in, you get pulmonary anthrax. You eat an infected cow, you get GI anthrax. You smear some bacterial spores in a cut, you get cutaneous anthrax. All three forms can kill you dead.

Corynebacterium diphtheriae
Diptheria comes in respiratory and cutaneous forms. The cutaneous form is pretty gross. Google it if you dare. Diptheria toxin gets into cells and inhibits their ability to make proteins, which is a pretty essential part of being a healthy and normal cell, resulting in cell death. As this is a generally bad thing, you get sick.

Streptococcus pyogenes
Not content to just produce a single toxin, this bacterium produces a whole wack of 'em. The most exciting of these are streptolysin O and S, which destroy blood cells. Toxins from this bacterium are responsible for a number of diseases, including strep throat, impetigo, scarlet fever, necrotizing fasciitis, and toxic shock syndrome.


Grayanotoxin - Turkish mad honey and third-degree heart block

  • also called andromedotoxin, acetylandromedol, and rhodotoxin by science people who can't seem to agree on one name (seriously, form a committee and get this sorted out, science people! I don't indirectly pay for some of your research for nothing, you know! I want clarity!)
  • sublimely synthesized by a considerable number of plants belonging to the family Ericaceae, in particular, several of those of the genus Rhododendron
  • is occasionally found in honey from Turkey (especially around the Black Sea) as a result of bees collecting nectar from certain species of Rhododendron that grow in the area
    • this honey is called 'mad honey' ('deli bal' in Turkish) and people have been reporting that it makes them puke since 401 BCE
    • mad honey is still a common source of food poisoning in Turkey, likely because it is also used as an alternative medicine AND there is an increasing demand for 'natural' products
    • the locals can apparently tell when the honey is poisonous, as it causes a burning sensation in the throat following consumption
  • binds to and inhibits the closing of (i.e. persistently activates) sodium channels, causing excitable tissues (muscle and nerve) to become overexcited (due to sustained depolarization)
    • this can lead to things like muscle weakness, puking, excess sweating and salivating, and in cases of more severe poisoning, potentially life-ending heart problems like third-degree atrioventricular (AV) block as well as seizures and hypotension
Gunduz A, Turedi S, Uzun H, Topbas M. Mad honey poisoning. Am J Emerg Med. 2006 Sep;24(5):595-8.


Capsaicin - A cause of and a cure for pain

  • the main compound in chili peppers (genus Capsicum) that makes them so gosh darn spicy
    • the hottest chili in the world is the Naga Jolokia (I know you were wondering)
    • is one of six natural capsaicinoids found in chili peppers, all of which produce a wonderful burning sensation when they come in contact with mucous membranes
  • the burning sensation it produces is due to it activating vanilloid receptor subtype 1 (TRPV1), a type of ionotropic receptor found on neurons called C-fibres that carry pain signals (particularly those associated with excessive heat or abrasive damage, in other words, things that produce a burning sensation) to the brain
    • does not actually cause tissue damage, instead produces the sensation of it by hijacking the neural pathway by which the sensation is transmitted to the brain
  • has been used to treat peripheral pain (pain not originating in the brain or spinal cord) associated with conditions including rheumatoid arthritis, diabetic neuropathy, and postherpetic neuralgia (pain occurring after a bout with shingles)
  • topical preparations (ointments, creams) have been used for minor inflammatory joint and muscle pain
  • can also be used to treat perennial nonallergic rhinitis (PNAR), which is essentially hay fever only the afflicted individual has no known sensitivities to specific allergens (e.g. pollen)
  • in all of these applications, the administration of capsaicin initially worsens the condition being treated due to the stimulation of C-fibres, but with repeated administration is thought that the C-fibres get overstimulated such that they become depleted of the neurotransmitters and neuropeptides (e.g. substance P) that mediate their actions, leading to the loss of pain sensation and neurogenic (neuron-sourced) inflammation/reduced nasal hyperreactivity (congestion and runny nose)
    • a typical treatment regime involves first the application of a topical anaesthetic followed by capsaicin in order to avoid the burning sensation it produces
  • is neat because it represents an analgesic that is neither an NSAID nor an opioid and one that acts directly and selectively on pain transmitting neurons
  • currently under investigation as a possible treatment for diabetes and cancer
  • has been claimed to have antigenotoxic and anticarcinogenic effects by some researchers, yet has been reported to be a tumour promoter and carcinogen by others (the jury is still very much out on this one)
    • is bioactivated by CYP2E1 (a drug-metabolizing enzyme) to reactive species that are capable of binding to the enzyme and potentially to DNA, which would be expected to cause mutations that could lead to the development of cancer
- Greiner AN, Meltzer EO. Pharmacologic rationale for treating allergic and nonallergic rhinitis. J Allergy Clin Immunol. 2006 Nov;118(5):985-98.
- Szolcsanyi J. Forty years in capsaicin research for sensory pharmacology and physiology. Neuropeptides. 2004 Dec;38(6):377-84.
- Zhou S et al. Herbal bioactivation: the good, the bad and the ugly. Life Sci. 2004 Jan 9;74(8):935-68.


Gyromitrin - Choose your mushrooms wisely

  • toxic hydrazine derivative found primarily in the mushrooms Gyromitra esculenta, Gyromitra fastigiata, Gyromitra ambigua and Helvella lacunosa
    • these species are referred to as false morels, since they resemble in their appearance the true morels, which are yummy non-poisonous mushrooms belonging to the genus Morchella, and all appear very early on in the springtime
  • volatile and water soluble, such that mushrooms containing it can usually be rendered safely edible by cuttin' 'em up into wee liddle pieces and then boiling or pan-frying the bejesus of of 'em (releasing the toxin into the water or air)
  • metabolized (by hydrolysis) in the body first to methyl-N-formylhydrazine (MFH) and then on to monomethylhydrazine (MMH)
    • MFH causes liver necrosis (widespread cell death), which can lead to liver and kidney failure
    • MMH can cause seizures (often to the point of status epilepticus) by inhibiting the formation of GABA, the primary inhibitory neurotransmitter in the brain (less GABA = increased propensity for the brain to become overexcited and throw a seizure)
    • it inhibits GABA formation by reacting with and so depleting pyridoxal-5-phosphate, which is the active form of vitamin B6 and a required coenzyme for the synthesis of GABA from glutamate by the enzyme glutamic acid decarboxylase (GAD)
    • these seizures are resistant to benzos (just like seizures caused by isoniazid overdose)
    • may be able to treat poisoning (at least the seizures) with pyridoxine (another form of vitamin B6)
  • has been shown to be carcinogenic in lab animals (even in very small doses) but there are no reports of it causing cancer in humans
Berger KJ, Guss DA. Mycotoxins revisited: Part II. J Emerg Med. 2005 Feb;28(2):175-83.


Trippin' in your own backyard: Psychedelic drugs in plants and fungi found naturally in the USA

First off, apologies in advance for the exclusive focus on the United States in this post. I realize that many of you aren't from the US of A. Heck, I'm not. But I found a cool article on PubMed and I thought you people might find it interesting. So I've summarized it for y'all. Don't know about you, but I have a tendency to associate drug-containing plants and fungi with exotic locales. Anticancer drugs from the rain forest. Opium from Afghanistan. Cocaine from Columbia. That sort of thing. So when I came across an article on drugs, psychedelic drugs no less, found in plants and fungi that have established themselves in American soil, I was intrigued. Please note that I will be discussing species that are growing wild, not those being cultivated in greenhouses and suburban basements.

The short-acting hallucinogen DMT, most often associated with the Amazonian brew ayahuasca, is also present in appreciable quantities in several common species of grass belonging to the genus Phalaris, including Phalaris aquatica (canarygrass, Harding Grass). These grasses can be found hanging out in the fields, sidewalk cracks, abandoned parking lots, and poorly-maintained lawns of Middle America. DMT is also found in the root bark of Desmanthus illinoensis (prairie bundleflower), which is also found throughout the Land of Liberty.

Psilocybin and psilocin are hallucinogens found in a number of mushrooms belonging to the genus Psilocybe. While these 'magic mushrooms' are generally associated with Mexico, where they used religiously by the native peoples of Mesoamerica, they are also found growing on cow and horse poop in the USA. That's right folks, shrooms are coprophagous (they grow on and consume feces). So the next time you eat some, try not to think about that. Bad trip. As far as localization goes, they are generally found along the coastlines of the Gulf of Mexico (Florida to Texas) and Pacific Northeast (California to Washington).

In the desert along the Texas-Mexico border, you can find Lophophoria williamsii (peyote). This spineless cactus is the natural source of mescaline, a hallucinogen enjoyed by luminaries such as Aldous Huxley and Eli Cash.

Lysergic acid amide (LSA), a natural analogue of LSD, is found in the seeds of of Argyreia nervosa (Hawaiian baby woodrose) and several members of the genus Ipomoea (morning glory). The woodrose is found only in Hawaii, having been introduced from Asia, while morning glory plants are found across the US. LSA is also present in Stipa robusta (sleepygrass), which is found in the American southwest.

In addition to the classic hallucinogens, there are a number of drugs capable of producing a toxic delirium that features hallucinations. These so-called dissociative agents are generally much more dangerous than the hallucinogens. Atropine and scopolamine, anticholinergic dissociative agents, are found in a number of plants belonging to the Solanaceae family that grow wild in the States. These include Datura stamonium (Jimson weed), Atropa belladonna (deadly nightshade), and Mandragora officinarum (mandrake), and Hyoscyamus niger (henbane). Of these, only plants of the genus Datura are native to the United States, the rest having being introduced due to their pretty flowers or something. Mushrooms of the genus Amanita, found throughout Canada's southern neighbour (ha, eat my Canadian spelling, suckas!), contain the dissociative agents ibotenic acid, muscimol, and muscazone. Unfortunately, some species also contain fun toxins like α-amanitin, which can cause lethal liver and kidney damage. These ones usually have scary names like death cap and destroying angel. Arguable the best known Amanita mushroom is Amanita muscaria, which looks pretty darn cool.

Halpern JH. Hallucinogens and dissociative agents naturally growing in the United States. Pharmacol Ther. 2004 May;102(2):131-8.



  • analgesic (killer of pain) and cardiotoxin (causes arrhythmias) found in plants belonging to the genus Aconitum (otherwise known as aconite, monkshood, or wolfsbane)
    • wolfsbane sounds awesome (see also: henbane)
    • its cardiotoxicity prevents it from being used therapeutically as an analgesic
    • extracts of these plants are used in traditional Chinese medicine to treat pain and inflammation, a great example of how natural/herbal remedies are often more dangerous than the drugs they replace
    • is occasionally intentionally used to poison people
  • is thought to bind to and open voltage-dependent sodium channels in the heart and central nervous system, resulting in the disruption of electrical conduction in the heart (producing arrhythmias) and pain signals to the brain (producing analgesia)
  • used to create animal models of cardiac arrhythmia, which help researchers to develop new antiarrhythmic agents (yay!)
Gutser UT et al. Mode of antinociceptive and toxic action of alkaloids of Aconitum spec.. Naunyn Schmiedebergs Arch Pharmacol. 1998 Jan;357(1):39-48.



  • monoterpene (like menthol or pulegone) that exists in two related forms, alpha and beta
  • present in a number of plants, most notably grand wormwood (Artemisia absinthium), a shrub native to Europe, Asia, and northern Africa that is used to make absinthe
    • also found in Salvia officinalis (sage), Salvia sclarea (clary), Tanacetum vulgaris (tansy) and members of the genus Juniperus (junipers)
    • absinthe ("green fairy" or "fée verte" for my French-speaking readers) is a highly alcoholic (damn straight!) emerald-green spirit that was arguably the most popular spirit drink in Europe in the late 19th century
      • French soldiers fighting in Algeria in the mid 19th century were given alcoholic drinks containing wormwood to protect them from infectious diseases and increase morale, leading to boom in the popularity of absinthe as they returned home having developed a taste for the stuff
      • although popular with all levels of society, was especially revered by the artists (see: Degas, van Gogh, Picasso) and intellectuals (Verlaine, Wilde, Poe, Hemingway)
      • was banned throughout Europe and North America in the early 20th century due to it being linked (often erroneously) to all sorts of diseases including a syndrome called "absinthism" that featured hallucinations, blindness, convulsions, general nuttiness, and even death
    • besides absinthe, the major dietary source of thujone is actually sage and sage-containing products
  • has a chemical structure that is similar to tetrahydrocannabinol (THC) but it does not act on cannabinoid receptors
  • blocks GABA-A receptors, which normally keep the brain from becoming overactive by inhibiting neural activity, resulting in abnormal excitability (excitotoxicity) producing muscle spasms and convulsions
- Lachenmeier DW et al. Absinthe--a review. Crit Rev Food Sci Nutr. 2006;46(5):365-77.
- Rietjens IM et al. Molecular mechanisms of toxicity of important food-borne phytotoxins. Mol Nutr Food Res. 2005 Feb;49(2):131-58.


The ULTIMATE toxin list

That's right. I've been working away at this little beauty, and it's time to share. It's still in early development, but hopefully it will soon grow into something that will make it worthy of it's namesake. I'm thinking about making some more lists.

Check it out.


Resiniferatoxin (RTX)

  • analogue of capsaicin, the stuff in chili peppers (genus Capsicum) that makes them so friggin' hot
  • present in high concentrations in the sap of the resin spurge (Euphorbia resinifera), a plant that looks very much like a cactus that is native to Morocco and the Canary Islands
  • along with capsaicin, is able to excite and then desensitize type C afferent fibres (pain-transmitting pathways to the brain and spinal cord) by activating a particular type of calcium channel that is expressed selectively in these fibres
    • the initial excitation of these fibres is responsible for the burning sensation experienced with eating chili peppers and getting sprayed with pepper spray
    • by desensitizing the fibres, the transmission of pain is disrupted, producing an analgesic (painkilling) effect
    • RTX is several thousands times more potent in desensitizing the fibres, making it a potential powerful analgesic agent (drugs based on RTX are currently in development) since it can be given in small enough doses that the initial excitation (and pain) is negligible
  • effective means of increasing bladder capacity in individuals afflicted with neurogenic detrusor overactivity (NDO) of spinal origin
    • NDO is a condition featuring involuntary contractions of the detrusor muscle (the muscular coat of the bladder) while the bladder is filling with pee, causing you to feel like you have to pee a lot and piss yourself because you can't hold it
    • the desensitization of type C fibres that innervate the bladder depresses the activity of the muscle so that it doesn't contract as often
Silva C et al. Urodynamic effect of intravesical resiniferatoxin in patients with neurogenic detrusor overactivity of spinal origin: results of a double-blind randomized placebo-controlled trial. Eur Urol. 2005 Oct;48(4):650-5.


Podophyllotoxin (Podofilox)

  • non-alkaloid lignan toxin present in podophyllin, resin produced by the rhizomes of plants belonging to the genus Podophyllum, for which it and the aforementioned resin are named, as well as a number of other genera that I don't feel like listing since I'm pretty sure most of you don't care that much and I really, really want to avoiding bogging down my posts with boring information and hideously long-winded sentences
    • plants containing lignans are commonly found in traditional medicine, making them interesting starting points for the development of new drugs
    • the genus Podophyllum includes Podophyllum peltatum (American Mayapple), a perennial herb native to eastern North America that grows in colonies
  • is used as a topic antiviral agent in the treatment of condyloma acuminatum (genital warts!) caused by human papilloma virus as well as other types of warts found on one's naughty bits
  • has also been used in the treatment of psoriasis vulgaris and rheumatoid arthritis
  • kills cancer cells but was found to be too toxic in mice in preclinical trials, the step in drug development when compounds are evaluated in animals before trying them out in humans
    • etoposide, teniposide, and etopophos are anticancer drugs derived from podophyllotoxin that permanently inactivate DNA topoisomerase II, resulting in DNA strand breaks (i.e. damage) that eventually lead to cell death, but have no effects on the polymerization of tubulin
Gordaliza M et al. Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives. Toxicon. 2004 Sep 15;44(4):441-59.


Sodium fluoroacetate

  • other, much cooler name: Compound 1080
  • naturally occurring poison found in a number of plants from around the world
  • converted in the body to to fluorocitrate, which disrupts the citric acid cycle, thus impairing cellular respiration
    • this is very bad
    • since it messes up an essential component of metabolism, there is no known antidote and few people survive significant ingestion of this substance
  • discovered by the Germans during World War II
    • they were looking for new chemical warfare agents
    • highly potent (0.1 g can theoretically kill a man) but requires ingestion or injection to be effective, so not quite what they were looking for (inhalation is where it's at!)
    • independently discovered by the Americans during the war and was introduced as a rodenticide (kills...rodents) in the US in 1946
  • currently is used by farmers to kill various crop- and livestock-eating mammals
  • is also highly toxic to birds and insects
Proudfoot AT, Bradberry SM, Vale JA. Sodium fluoroacetate poisoning. Toxicol Rev. 2006;25(4):213-9.



  • monoterpene present in essential oils (see: silly aromatherapy nonsense) from plants of the Lamiaceae (mint) family
    • particularly high levels are found in the European (Mentha pulegium) and American (Hedeoma pulegioides) varieties of pennyroyal
  • has an odour similar to peppermint and camphor
  • used as a flavouring agent, an ingredient in perfumes, and a flea repellent (so perfect for hippies)
  • pennyroyal tea (and oil) is/was used in traditional folk medicine to promote menstruation and as an abortifacient to initiate self-abortion
    • there is a crappy Nirvana song about this (bring it, haters!)
    • there is no scientific evidence available to support its efficacy in this regard (read: this is a bad idea)
  • ingestion of high doses has been reported to cause organ toxicity and death
  • pulegone and one of its metabolites (menthofuran) are bioactivated by liver enzymes to reactive intermediates that permanently bind to cellular proteins and cause liver damage
Anderson IB et al. Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature. Ann Intern Med. 1996 Apr 15;124(8):726-34.


Toxins from mammals

Snakes and frogs are obvious examples of animals that are capable of producing venom, which they tend to employ to capture prey and/or defend against predators. However, one does not generally associate mammals with being venomous (unless of course, one is a mammalogist or is exceptionally good with trivia). Truly I say to you, several mammals, members of the order Insectivora, are actually venomous. These creatures produce toxins in their salivary glands that are secreted along with, and so present in, their saliva. They include the platypus, the Haitian solenodon, the slow loris, and several species of shrew. In case you were wondering, shrews have five toes, while rodents have four. Here's the breakdown:

Blarina toxin

The venomous saliva of northern short-tailed shrew (Blarina brevicauda), which is native to North America and is roughly the size of a house mouse, is known to contain at least one toxic compound, blarina toxin (BLTX). This shrew is an insatiable little bugger, eating almost constantly due to its incredibly high metabolic rate. It is thought that it uses its venomous saliva to paralyze and catch prey larger than itself, such as rodents and frogs, in order to satisfy its extreme hunger.

BLTX is a tissue kallikrein-like protease, an enzyme capable of cleaving kinins, such as bradykinin, from precursor proteins known as kininogens (think getting a cheque in the mail and having to separate it from its attached piece of paper in order 'activate' it for deposit). Bradykinin produces vasodilatation, contraction of smooth muscle, increased vascular permeability, and pain. In mice, BLTX causes rapid and irregular respiration, hypotension, hind limb paralysis, and convulsions in mice, with death generally occurring 3-5 hr after exposure. I'm guessing that the respiratory difficulties and hypotension are at least partly the result of systemic vasodilatation and bronchial constriction mediated by bradykinin released by the toxin. The actual mechanism by which the venom causes death is still unknown. Since humans are much larger than rodents and frogs, if we are bitten by B. brevicauda the quantity of venom is presumably insufficient to produce a systemic reaction, such that only a local inflammation (burning sensation, redness, swelling), likely due to BLTX-mediated bradykinin release, is observed where the bite took place.

Platypus venom

Not only is the Australian duck-bill platypus (Ornithorhynchus anatinus) one of only five species of mammals that lay eggs, it is also one of the few mammals that produce venom. Male platypuses possess spurs on their hind limbs which they use to deliver a venom produced in pelvic venom glands as an offensive and defensive weapon. Envenomation (getting the venom injected into you) causes a severe localized response featuring intense pain, hyperalgesia (increased sensitivity to pain), and plasma extravasation (swelling due to fluid entering the tissue from blood vessels). When administered systemically to lab animals, the venom causes hypotension (decrease in blood pressure) and peripheral vasodilatation (increased blood flow to the skin and other body surfaces). The mechanisms by which these effects are produced is unknown.

Platypus venom is known to contain at least 19 different peptide/protein components, including two C-type natriuretic peptides (OvCNPa and OvCNPb) and four defensin-like peptides (DLPs). C-type natriuretic peptides are naturally produced by endothelial cells (form the innermost layer of blood vessels) in mammals and have been found in brain, intestine, and kidney. Their primary function is thought to be to regulate blood flow by causing vasodilatation. These peptides have been found in the venom of the South American pit viper, suggesting that they are capable of producing toxic effects as well. Defensins are small peptides found in a wide variety of invertebrates and vertebrates that are capable of killing bacteria, fungi, and viruses. Interestingly, the DLPs in platypus venom have not been shown to possess antimicrobial activity, suggesting they may have a role in mediating the toxic effects of the venom instead.

OvCNPa and OvCNPb have been shown to cause the release of histamine from mast cells, an important process in the development of inflammation. This would explain the swelling and increased sensitivity to pain. Additionally, platypus venom is capable of causing the formation of voltage-dependent ion channels in artificial cell membranes, with OvCNPa and OvCNPb having been shown to have a role in this phenomenon. It has been suggested that these channels, by altering membrane potentials and/or the movement of calcium ion across cell membranes, can modulate signal transduction pathways in cells so as to adversely affect cellular functions.

Kita M, Nakamura Y, Okumura Y, Ohdachi SD, Oba Y, Yoshikuni M, Kido H, Uemura D. Blarina toxin, a mammalian lethal venom from the short-tailed shrew Blarina brevicauda: Isolation and characterization. Proc Natl Acad Sci USA. 2004 May 18;101(20):7542-7.

Kourie JI. Characterization of a C-type natriuretic peptide (CNP-39)-formed cation-selective channel from platypus (Ornithorhynchus anatinus) venom. J Physiol. 1999 Jul 15;518 (Pt 2):359-69.

Torres AM et al. Mammalian l-to-d-amino-acid-residue isomerase from platypus venom. FEBS Lett. 2006 Mar 6;580(6):1587-91.



  • nephrotoxin produced by moulds belonging to the genera Aspergillus and Penicillium
  • actually refers to three related compounds, designated A, B, and C (scientists are a wild and crazy bunch when it comes to naming things, I tell you what)
  • ochratoxin A is the best studied of the three, and has been found in cereal grains, coffee, cocoa beans, dried fruit, and red wine
  • is thought to be the cause of 'Balkan nephropathy', a condition featuring chronic kidney dysfunction progressing to kidney failure and/or cancer of the kidney that is particularly common in certain rural areas of the Balkan countries for some reason
Timbrell, John. The Poison Paradox. New York: Oxford Unversity Press, 2005.


Teh Overdose: Drugs and poisons that you shouldn't kill yourself with

Disclaimer: Yes, this post is pretty tasteless. However, it should be noted that I am in no way condoning suicide with this post. I am, in fact, merely pointing out why overdosing on the following compounds is a really bad idea.

Also commonly known as paracetamol, APAP, and Tylenol, is the most common cause of intentional self-poisoning in adults since it is widely available and cheap. What doesn't appear to be well known is that at high doses this drug is selectively toxic to the liver. If you end up dying, it is only after spending several days in intense pain. This form of poisoning can be treated with N-acetylcysteine (NAC).

A bipyridylium herbicide found in many weed control products (e.g. Gramoxone), if ingested in sufficiently large quantities it will cause multisystem organ failure with death occurring within hours to a few days. However, should you fail to drink enough of it, it will selectively accumulate and persist in your lungs and slowly digest them while you spend several weeks gasping for breath in terrible pain before you expire. There is currently no antidote, and even people who manage to get lung transplants find that their new lungs are eventually destroyed as well, since the poison also hangs out in the fat surrounding them.

Tricyclic Antidepressants (TCAs)
In overdose, these drugs (amitriptyline, imipramine, desipramine, etc.) make you very sick. You got your cardiac toxicity (arrhythmias are the usual cause of death), neutoxicity (seizures and coma), and hypotension. Plus a whole lots of anticholinergic effects going on. Not a peaceful way to go.

As was discussed previously, a painful and terrifying way to die. You remain fully conscious and coherent as you experience repeated bouts of violent convulsions until your breathing eventually stops and you asphyxiate.


1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

  • thermal breakdown product of a meperidine-like synthetic opioid called 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP) that is used by drug addicts as a heroin substitute and may be accidentally produced during the synthesis of MPPP
  • produces severe Parkinsonian symptoms in humans and primates (the humans are often addicts who unwillingly inject themselves with some MPTP-laced MPPP)
    • hallucinations and near total immobility ('the frozen addict')
  • is transformed in the brain to MPP+ (1-methyl-4-phenylpyridinium, in case you were wondering), which selectively destroys dopamine-releasing neurons in the substantia nigra, the area of the brain that is damaged in people with Parkinson's disease
  • in 1982, six people in San Jose, California were exposed to MPTP and developed Parkinson's disease - one of the docs who examined them wrote a book about his experiences
  • is used to generate a model for Parkinson's disease in lab animals, permitting the study of the disease and the development of ways to treat it
Singer TP, Salach JI, Castagnoli N Jr, Trevor A. Interactions of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine with monoamine oxidases. Biochem J. 1986 May 1;235(3):785-9.



  • neurotoxic (bad fer teh brain) protein present in the venom of widow spiders (members of the genus Latrodectus) including the infamous black widow
  • one of seven latrotoxins, is the only one that is vertebrae-specific (only affects animals with a spine, so my chemistry prof should be safe! OH SNAP!), the others being primarily active against insects (the natural prey of the spiders) or crustaceans
  • the current theory is that four units of the protein can join together to form pores in cells, with the resulting changes in ion flux signalling the release of neurotransmitters from nerve cells, producing (among other things) muscle contraction, manifested as painful abdominal cramps and breathing difficulties