Neutralization of cardiac toxins oleandrin, oleandrigenin, bufalin, and cinobufotalin by digibind: monitoring the effect by measuring free digitoxin concentrations.
Oleandrin plant poisoning is common in children and the plant extract is used in Chinese medicines. The toxicity is due to oleandrin and the deglycosylated metabolite oleandrigenin. Bufalin and cinobufotalin (toad cardiac toxins) are also widely used in Chinese medicines like Chan SU, and Lu-Shen -WU. Severe toxicity from bufalin after consumption of toad soup has been reported. Taking advantage of structural similarities of these toxins with digitoxin, we demonstrated that these compounds can be rapidly detected in blood by the fluorescence polarization immunoassay for digitoxin. The cross reactivities of these compounds with digoxin assay were much lower. For example, when a drug free serum was supplemented with 10 microg/ml of oleandrin, we observed 127.7 ng/ml of digitoxin equivalent but only 2.4 ng/ml of digoxin equivalent concentration. Digibind neutralized all cardiac toxins studied as evidenced by significant fall of free concentrations. When aliquots of serum pool containing 50.0 microg/ml of oleandrin were supplemented with 0, 10.0, 25.0, 50.0, 100, and 200 microg/ml of digibind, the mean free concentrations were 30.6, 23.3, 16.0, 10.7, 7.8 and 5.5 microg/ml respectively. Similarly, with 50.0 microg/ml of oleandrigenin (total concentration: 36.2 ng/ml), the free concentration was 14.5 ng/ml digitoxin equivalent in the absence of digibind and 5.4 ng/ml in the presence of 200 microg/ml of digibind. In another specimen containing 500 ng/ml bufalin (total concentration: 156.9 ng/ml), the free concentration was 8.6 ng/ml in the absence of digibind and none detected in the presence of 100.0 microg/ml digibind. Because such neutralization may also occur in vivo, digibind may be useful in treating patients exposed to these toxins.
Dasgupta
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A
Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, 77030, USA.
Emerson
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L
D002018:Bufanolides / Q000032:analysis / Q000097:blood; D002298:Cardenolides / Q000032:analysis / Q000097:blood; D002316:Cardiotonic Agents / Q000032:analysis* / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003429:Cross Reactions; D004074:Digitoxin / Q000032:analysis / Q000097:blood; D004077:Digoxin / Q000276:immunology; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000378:metabolism*; D013058:Mass Spectrometry; D009500:Neutralization Tests
D002018:Bufanolides; D002298:Cardenolides; D002316:Cardiotonic Agents; D007140:Immunoglobulin Fab Fragments; C050199:digoxin antibodies Fab fragments; C008701:oleandrigenin; D004077:Digoxin; D004074:Digitoxin; C021065:oleandrin; C063451:cinobufotalin; C022777:bufalin