|Jmol-3D images||Image 1|
|Molar mass||444.56 g mol−1|
|LD50||4.13 mg·kg−1 (mouse, intravenous)
0.4 mg·kg−1 (mouse, subcutaneous) 0.136 mg·kg−1 (cat, intravenous)
|Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)|
|(what is: / ?)|
Bufotalin is part of Ch'an Su, a traditional Chinese pharmacy and its used for cancer therapies. Researchers recently reveald that bufotalin induces apoptosis in human hepatocellular carcinoma Hep 3B cells and might involve caspases and AIF(Apoptosis inducing factor), that's why it could be used in terms of cancer treatment. 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.
Bufotalin is part of the traditional Chinese ch'an su, it is also known as Venenum Bufonis or senso (Japanese). Bufotalin can be extracted from the skin parotoid glands of the Common European toad (Bufo bufo).It is especially of research interest, as it is one of Chan su’s most potent active compounds, that at the same time as it is not that toxic, as the other bufanolide substances.
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.
Mechanism of action
Bufotalin is found to inhibit myocardial Na+/K+ ATPase activity by that increasing myocardial contractile force. Furthermore bufotalin was not found to affect the heart-rate with those changes in myocardial Na+/K+ ATPase activity. Bufotalin which structure looks like the one of digitalin and digitoxin, shows effects on cardiovascular system as well. 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.
The mechanism of the biotransformation of bufotalin is still unknown. Researches found, that bufotalin is biotransformed into at least 5 different compounds.
If bufotalin is esterised with suberyl arginine the bufotalin like steroid bufotoxin is obtained.
- "Datasheet: Bufotalin sc-202509" Santa Cruz Biotechnology, Inc.http://datasheets.scbt.com/sc-202509.pdf
- Kwan, T; Paiusco, AD; Kohl, L (September 1992). "Digitalis toxicity caused by toad venom." (PDF). Chest 102 (3): 949–50. doi:10.1378/chest.102.3.949. PMID 1325343.
- Jan, SL; Chen, FL; Hung, DZ; Chi, CS (November–December 1997). "Intoxication after ingestion of toad soup: report of two cases.". Zhonghua Minguo xiao er ke yi xue hui za zhi 38 (6): 477–80. PMID 9473822.
- Su, CL; Lin, TY; Lin, CN; Won, SJ (14 January 2009). "Involvement of Caspases and Apoptosis-Inducing Factor in Bufotalin-Induced Apoptosis of Hep 3B Cells". Journal of Agricultural and Food Chemistry 57 (1): 55–61. doi:10.1021/jf802769g. PMID 19055367.
- Zhang, DM; Liu, JS; Tang, MK; Yiu, A; Cao, HH; Jiang, L; Chan, JY; Tian, HY; Fung, KP; Ye, WC (October 2012). "Bufotalin from Venenum Bufonis inhibits growth of multidrug resistant HepG2 cells through G2/M cell cycle arrest and apoptosis.". European Journal of Pharmacology 692 (1-3): 19–28. doi:10.1016/j.ejphar.2012.06.045. PMID 22841670.
- Spoerke, DG (November 1986). "Toad Toxins".
- Ma, Hongyue; Jiang, J; Zhang, J; Zhou, J; Ding, A; Lv, G; Xu, H; You, F; Zhan, Z; Duan, J (January 2012). "Protective effect of taurine on cardiotoxicity of the bufadienolides derived from toad (Bufo bufo gargarizans Canto) venom in guinea-pigs in vivo and in vitro". Toxicology Mechanisms and Methods 22 (1): 1–8. doi:10.3109/15376516.2011.583295. PMID 22150009.
- Garg, AD; Hippargi, RV; Gandhare, AN (2008). "Toad skin-secretions: Potent source of pharmacologically and therapeutically significant compounds". The Internet Journal of Pharmacology 5 (2). doi:10.5580/18b6.
- Yu, CL; Hou, HM (25 December 2010). "Plasma pharmacokinetics and tissue distribution of bufotalin in mice following single-bolus injection and constant-rate infusion of bufotalin solution". European Journal of Drug Metabolism and Pharmacokinetics 35 (3-4): 115–121. doi:10.1007/s13318-010-0017-6. PMID 21302038.
- Waiwut, P; Inujima, A; Inoue, H; Saiki, I; Sakurai, H (January 2012). "Bufotalin sensitizes death receptor-induced apoptosis via Bid- and STAT1-dependent pathways." (PDF). International Journal of Oncology 40 (1): 203–8. doi:10.3892/ijo.2011.1182. PMID 21887462.
- Zhang, X; Ye, M; Dong, YH; Hu, HB; Tao, SJ; Yin, J; Guo, DA (October 2011). "Biotransformation of bufadienolides by cell suspension cultures of Saussurea involucrata.". Phytochemistry 72 (14-15): 1779–85. doi:10.1016/j.phytochem.2011.05.004. PMID 21636103.
- Ferreira, PM; Lima, DJ; Debiasi, BW; Soares, BM; Machado Kda, C; Noronha Jda, C; Rodrigues Dde, J; Sinhorin, AP; Pessoa, C; Vieira GM, Jr (September 2013). "Antiproliferative activity of Rhinella marina and Rhaebo guttatus venom extracts from Southern Amazon.". Toxicon 72: 43–51. doi:10.1016/j.toxicon.2013.06.009. PMID 23796725.
- Müller-Schwarze, D (2006). Chemical ecology of vertebrates. Cambridge: Cambridge University Press. p. 255. ISBN 978-0521363778.