Bufotalin is a cardiotoxic bufanolide

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

cardiac glycoside Cardiac glycosides are a class of organic compounds that increase the output force of the heart and decrease its rate of contractions by inhibiting the cellular sodium-potassium ATPase pump. Their beneficial medical uses include treatments for ...

analogue, secreted by a number of toad species. Bufotalin can be extracted from the skin

parotoid gland The parotoid gland (alternatively, paratoid gland) is an external skin gland on the back, neck, and shoulder of some frogs (especially toads), and salamanders. It can secrete a number of milky alkaloid substances (depending on the species) known ...

s of several types of toad.

Sources

'' Rhinella marina'' (Cane toad), '' Rhaebo guttatus'' (Smooth-sided toad), '' Bufo melanostictus'' (Asian toad), and ''

Bufo bufo The common toad, European toad, or in Anglophone parts of Europe, simply the toad (''Bufo bufo'', from Latin ''bufo'' "toad"), is a toad found throughout most of Europe (with the exception of Ireland, Iceland, parts of Scandinavia, and some Medi ...

'' (common European toad) are sources of bufotalin.

Traditional medicine

Bufotalin is part of Ch'an Su, a

traditional Chinese medicine Traditional Chinese medicine (TCM) is an alternative medicine, alternative medical practice drawn from traditional medicine in China. A large share of its claims are pseudoscientific, with the majority of treatments having no robust evidence ...

used for cancer. It is also known as Venenum Bufonis or senso (Japanese).

Toxicity

Specifically, in cats the lethal median dose is 0.13 mg/kg."Datasheet: Bufotalin sc-202509" ''Santa Cruz Biotechnology, Inc.''http://datasheets.scbt.com/sc-202509.pdf and in dogs is 0.36 mg/kg (intravenous). Knowing this it is advisable to monitor those functions continuously using an EKG. As there is no antidote against bufotalin all occurring symptoms need to be treated separately or if possible in combination with others. To increase the clearance theoretically, due to the similarities with digitoxin, cholestyramine, a bile salt, might help. Recent animal studies have shown that taurine restores cardiac functions. Symptomatic measures include

lignocaine Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia and ventricular fibrillation. When used for local anaesth ...

atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically give ...

and

phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anticonvulsant, anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence se ...

for cardiac toxicity and intravenous potassium compounds to correct hyperkalaemia from its effect on the Na⁺/K⁺ ATPase pump.

Pharmacology and mechanism of action

After a single intravenous injection, bufotalin gets quickly distributed and eliminated from the blood plasma with a half-time of 28.6 minutes and a MRT of 14.7 min. After 30 minutes after an administration of bufotalin, the concentrations within the brain and lungs are significantly higher than those in blood and other tissues. It also increases cancer cell's susceptibility to apoptosis via TNF-α signalling by the BH3 interacting domain death agonist and

STAT protein STAT, Stat., or stat may refer to: * stat (system call), a Unix system call that returns file attributes of an inode * ''Stat'' (TV series), an American sitcom that aired in 1991 * Stat (website), a health-oriented news website * STAT protein, ...

s. Bufotalin induces apoptosis ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' in human hepatocellular carcinoma Hep 3B cells and might involve caspases and apoptosis inducing factor (AIF). The use of bufotalin as a cancer treating compound is still in the experimental phase. It also arrests cell cycle at G(2)/M, by up- and down- regulation of several enzymes.

Pharmacokinetics

The mechanism of the biotransformation of bufotalin is still unknown. Researches found, that bufotalin is biotransformed into at least 5 different compounds. Biotransformation products of bufotalin

Chemical properties

If bufotalin is esterified with suberyl arginine, the bufotalin-like steroid

bufotoxin Bufotoxins are a family of toxic steroid lactones or substituted Substituted tryptamine, tryptamines of which some are toxic. They occur in the parotoid glands, skin, and poison of many toads (True toad, Bufonidae family) and other amphibians, an ...

is obtained.

References

{{Cardiac glycosides Amphibian toxins Bufanolides Acetate esters