Effects of Chan Su, a traditional Chinese medicine, on the calcium transients of isolated cardiomyocytes: Cardiotoxicity due to more than Na, K-ATPase blocking

Extracts of Chan Su, a traditional Chinese medication used as a topical anesthetic and cardiac medication, were incubated with cardiomyocytes that had been loaded with a calcium specific fluorescent probe. Calcium transients were measured by real-time fluorescence spectrophotometry following treatme...

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Bibliographic Details
Published in:Life sciences (1973) 2002-12, Vol.72 (6), p.699-709
Main Authors: Bick, Roger J, Poindexter, Brian J, Sweney, Roxanne R, Dasgupta, Amitava
Format: Article
Language:English
Subjects:
Amphibian Venoms - toxicity
Animals
Animals, Newborn
Bufadienolides
Bufanolides - pharmacology
Bufanolides - toxicity
Calcium
Calcium - metabolism
Cardiomyocytes
Cardiotonic Agents - toxicity
Cells, Cultured
Chan Su
Dose-Response Relationship, Drug
Drug Combinations
Enzyme Inhibitors - toxicity
Heart - drug effects
Medicine, Chinese Traditional
Myocardium - cytology
Myocardium - metabolism
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
Nifedipine - pharmacology
Ouabain - pharmacology
Rats
Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors
Traditional Chinese medicine
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Summary:Extracts of Chan Su, a traditional Chinese medication used as a topical anesthetic and cardiac medication, were incubated with cardiomyocytes that had been loaded with a calcium specific fluorescent probe. Calcium transients were measured by real-time fluorescence spectrophotometry following treatment. The transients were rapidly abolished following addition of a moderate concentration of the extract (400 ng/ml), resulting in high levels of intracellular calcium, while the lower amount (40 ng/ml) blocked the sodium-potassium adenosine triphosphatase. Treatments with ouabain and nifedipine were also made, either prior to, or after the addition of the Chan Su, in an attempt to better delineate the site(s) of action. The moderate concentration of Chan Su (400 ng/ml) extract caused the myocytes to cease beating within seconds of addition, even in experiments when saturating concentrations of nifedipine or ouabain had been previously added to the cells. As expected bufalin, the active component of Chan Su has similar effects. Our findings indicate that this compound is extremely cardiotoxic, even in small dose and acts rapidly to alter intracellular calcium stores in cardiomyocytes and possibly acts at sites other than the Na ++K + ATPase, either directly, or indirectly via changes in calcium concentrations.
ISSN:0024-3205
1879-0631
DOI:10.1016/S0024-3205(02)02302-0