Kullanıcı:Atom Karınca/Çalışma 2

Batrachotoxins (BTX) are extremely potent cardiotoxic and neurotoxic steroidal alkaloids found in certain species of frogs (poison dart frog), melyrid beetles, and birds (Pitohui, Ifrita kowaldi, Colluricincla megarhyncha). It is the most potent non-peptidal neurotoxin known.

Chemistry

Batrakotoksin, yunan alfabesinde kurbağa,toksin ve zehir anlamlarına gelen "batrachos" kelimesinden gelmiştir.Batrkotoksin, saf alkaloid'i izole edip yapısı ve kimyasal özelliklerini belirleyen bilim insanları John Daly ve Bernard Witkop tarafından adlandırıldı. Böylesine kuvvetli bir toksinle çalışmanın zorluğu ve elde edilebilen çok küçük miktarlar nedeniyle yapısı detaylı bir biçimde belirlenemedi. Ancak bağlantılı bir bileşik olan ve kristalize edilebilecek miktarlarda elde edilebilen Batrakotoksin A izole edildi ve yapısı x ışını kırınım tekniğiyle çözüldü. Batrakotoksin ve batrakotoksin A'nın mass spectra'sı karşılaştırıldığında ikisinin aynı "steroidal" yapıyı paylaştığı ve Batrachotoxin'in fazladan tek bir "pyrrole moiety" içeren Batrakotoksin A olduğu gözlemlendi. Batrakotoksin'in kimyasal formülü C₃₁H₄₂N₂O₆ olarak gösterilir.

More than 100 toxins have been identified from the skin secretions of members of the frog family Dendrobatidae, especially Dendrobates and Phyllobates. Members of the genus Dendrobates, Ranitomeya, and Oophaga are also known as "poison dart" or "poison arrow" frogs. However, only frogs of the genus Phyllobates produce the highly lethal batrachotoxin. The poison seeps through pores, hair folicles, and abrasions.

Batrakotoksin,1998'de başarıyla sentezlendi.

Toxicity

Extrapolating from the Şablon:LD50 in rats, the lethal dose of this alkaloid in humans is estimated to be 1 to 2 µg/kg. Thus, the lethal dose for a 68 kg (150 pound) person would be approximately 100 micrograms, or equivalent to the weight of two grains of ordinary (fine) table salt (NaCl). Batrachotoxin is thus around fifteen times more potent than curare (another arrow poison used by South American Indians and derived from plants of the genera Strychnos and Curarea), and about ten times more potent than tetrodotoxin, from the puffer fish. It is far less potent than botulinum toxin.

The toxin is released through colourless or milky secretions from glands located on the back and behind the ears of frogs from the genus Phyllobates. When one of these frogs is agitated, feels threatened or is in pain, the toxin is reflexively released through several canals.

As a neurotoxin it affects the nervous system. Neurological function depends on depolarization of nerve and muscle fibres due to increased sodium ion permeability of the excitable cell membrane. Lipid-soluble toxins such as batrachotoxin act directly on sodium ion channels involved in action potential generation and by modifying both their ion selectivity and voltage sensitivity.

This has a direct effect on the peripheral nervous system (PNS). Batrachotoxin in the PNS produces increased permeability (selective and irreversible) of the resting cell membrane to sodium ions, without changing potassium or calcium concentration. This influx of sodium depolarizes the formerly polarized cell membrane. Batrachotoxin also alters the ion selectivity of the ion channel by increasing the permeability of the channel toward larger cations. Voltage-sensitive sodium channels become persistently active at the resting membrane potential. Batrachotoxin kills by permanently blocking nerve signal transmission to the muscles.

In laymans terms, Batrachotoxin binds to and irreversibly opens the sodium channels of nerve cells such they cannot reset. The neuron is no longer capable of 'firing' (sending messages) and this results in paralysis.

Although generally classified as a neurotoxin, batrachotoxin has marked effects on heart muscles. These effects are similar to the cardiotoxic effects of digitalis (digoxin), a poison found in the foxglove plant. Batrachotoxin interferes with heart conduction, causing arrhythmias, extrasystoles, ventricular fibrillation and other changes which lead to cardiac arrest. Batrachotoxin induces a massive release of acetylcholine in nerves and muscles and destruction of synaptic vesicles, as well. Batrachotoxin R is more toxic than related batrachotoxinin A.

Structural changes in nerves and muscles are due to a massive influx of sodium ions, which produces osmotic alterations. It has been suggested that there may also be an effect on the central nervous system, although it is not currently known what such an effect may be.

Batrachotoxin activity is temperature-dependent, with a maximum activity at 37 degrees Celsius (98.6 degrees Fahrenheit). Its activity is also more rapid at an alkaline pH, which suggests that the unprotonated form may be more active.

Treatment

Currently no effective antidote exists for the treatment of batrachotoxin poisoning. Veratridine, aconitine and grayanotoxin—like batrachotoxin—are lipid-soluble poisons which similarly alter the ion selectivity of the sodium channels, suggesting a common site of action. Due to these similarities, treatment for batrachotoxin poisoning might best be modeled after, or based on, treatments for one of these poisons. Treatment may also be modeled after that for digitalis, which produces somewhat similar cardiotoxic effects.

While it is not an antidote, the membrane depolarization can be prevented or reversed by either tetrodotoxin (from puffer fish), which is a noncompetitive inhibitor, or saxitoxin ("red tide"). These both have effects antagonistic to those of batrachotoxin on sodium flux. Certain anesthetics may act as receptor antagonists to the action of this alkaloid poison, while other local anesthetics block its action altogether by acting as competitive antagonists.

Source

The "poison dart" (or "poison arrow") frog does not produce batrachotoxin itself. It is believed that the frogs get the poison from eating beetles or other insects in their native habitat. Frogs raised in captivity do not produce batrachotoxin, and thus may be handled without the risk of death.

The native habitat of poison dart frogs is the warm regions of Central America and South America, in which the humidity is around 80 percent.

Of the three so-called "poison dart" frogs which contain batrachotoxin—Phyllobates terribilis, Phyllobates aurotaenia, and Phyllobates bicolor—the most toxic is the most recently discovered Phyllobates terribilis, which generally contains 27 times more batrachotoxin than its close relatives and is 20-fold more toxic.

Also in 1990, it was discovered that some bird species in New Guinea, such as the Hooded Pitohui, contain the toxin on their skin and feathers. Like the dart frogs, it is believed they ingest the toxin from a food source and then secrete it. Specifically, the toxin has been recently discovered in melyrid beetles from New Guinea (the genus Choresine), making them the likely source of the toxin in the birds that consume them.

Use

Ayrıca bakınız: Arrow poison ve Blowdart

The most common use of this toxin is by the Noanamá Chocó and Emberá Chocó Indians of western Kolombiya for poisoning blowgun darts for use in hunting.

Zehirli oklar Chocó Amerindian'lar tarafından bir parça tahtanın kurbağaya sürmesiyle yapılır. By some accounts, the frog is then held over or roasted alive over a fire until it cries in pain. Bubbles of poison form as the frog's skin begins to blister. The dart tips are prepared by touching them to the toxin, or the toxin can be caught in a container and allowed to ferment. Poison darts made from either fresh or fermented batrachotoxin are enough to drop monkeys and birds in their tracks. Nerve paralysis is almost instantaneous.

Other accounts say that a stick siurukida ("bamboo tooth") is put through the mouth of the frog and passed out through one of its hind legs. This causes the frog to perspire profusely on its back, which becomes covered with a white froth. The darts are dipped or rolled in the froth, preserving their lethal power for up to a year.

References