digitoxin and oleandrigenin

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.

Topics: Bufanolides; Cardenolides; Cardiotonic Agents; Chromatography, High Pressure Liquid; Cross Reactions; Digitoxin; Digoxin; Humans; Immunoassay; Immunoglobulin Fab Fragments; Mass Spectrometry; Neutralization Tests

Toxicity from ingestion of the oleander plant is common. Oleandrin, the oleander glycoside, has structural similarity to cardiac glycoside digoxin and is known to cross react with various digoxin immunoassays. The authors studied the cross reactivity of oleandrin and its deglycosylated congener oleandrigenin with a fluorescence polarization immunoassay for digitoxin and compared their results with a new chemiluminescent assay for digitoxin on the Automated Chemiluminescent System (ACS:180 Plus) from Chiron Diagnostics. Even though the chemiluminescent assay has been reported to be comparable with the fluorescence polarization assay among normal patient population, oleandrin and oleandrigenin showed very high cross reactivities with the fluorescence polarization immunoassay and minimal cross reactivity with the new chemiluminescent assay. When the authors supplemented a serum specimen containing no digitoxin with 50 micrograms/ml of oleandrin, the fluorescence polarization assay recorded a value of 535.7 ng/ml of digitoxin equivalent, whereas the new chemiluminescent assay recorded a value of 10.3 ng/ml of digitoxin equivalent. The cross reactivity of oleandrigenin with the fluorescence polarization immunoassay for digitoxin was significantly lower than oleandrin. The presence of oleandrin also falsely elevated total digitoxin level in a specimen supplemented with digitoxin and oleandrin. The authors also measured free digitoxin concentration by the fluorescence polarization immunoassay in the ultrafiltrate of serum supplemented with digitoxin and oleandrin. Because digitoxin and oleandrin are bound strongly to protein, monitoring free digitoxin concentration by the fluorescence polarization immunoassay instead of total digitoxin concentration does not eliminate oleandrin interference. The authors conclude that fluorescence polarization immunoassay for digitoxin has a high cross reactivity with oleandrin and can falsely elevate digitoxin concentration in the presence of oleandrin, whereas the new chemiluminescent assay for digitoxin is almost free from interferences from oleandrin.

Topics: Anti-Arrhythmia Agents; Cardenolides; Cross Reactions; Digitoxin; Fluorescence Polarization Immunoassay; Immunoassay; Luminescent Measurements

Topics: Acetyldigoxins; Cardenolides; Digitalis; Digitalis Glycosides; Plant Extracts