Bufotalin

Bufotalin is a cardiotoxic bufanolide steroid, cardiac glycoside analogue, secreted by a number of toad species. Bufotalin can be extracted from the skin parotoid glands of several types of toad.

Traditional medicine
Bufotalin is part of Ch'an Su, a traditional Chinese medicine 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. 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, atropine and phenytoin 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 proteins.

Bufotalin induces apoptosis in vitro 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.

Chemical properties
If bufotalin is esterified with suberyl arginine, the bufotalin-like steroid bufotoxin is obtained.