Rapid detection of convallatoxin using five digoxin immunoassays

Abstract

CONTEXT Cardiac glycosides of plant origin are implicated in toxic ingestions that may result in hospitalization and are potentially lethal. The utility of commonly available digoxin serum assays for detecting foxglove and oleander ingestion has been demonstrated, but no studies have evaluated the structurally similar convallatoxin found in Convallaria majalis (lily of the valley) for rapid laboratory screening, nor has digoxin immune Fab been tested as an antidote for this ingestion. OBJECTIVE We aimed to (1) evaluate multiple digoxin assays for cross-reactivity to convallatoxin, (2) identify whether convallatoxin could be detected in vivo at clinically significant doses and (3) determine whether digoxin immune Fab could be an effective antidote to convallatoxin. MATERIALS AND METHODS Cross-reactivities of purified convallatoxin and oleandrin with five common digoxin immunoassays were determined. Serum from mice challenged with convallatoxin was tested for apparent digoxin levels. Binding of convallatoxin to digoxin immune Fab was determined in vitro. RESULTS Both convallatoxin and oleandrin were detectable by a panel of commonly used digoxin immunoassays, but cross-reactivity was variable between individual assays. We observed measurable apparent digoxin levels in serum of convallatoxin intoxicated mice at sublethal doses. Convallatoxin demonstrated no binding by digoxin immune Fab. CONCLUSION Multiple digoxin immunoassays detect botanical cardiac glycosides including convallatoxin and thus may be useful for rapid determination of severe exposures, but neutralization of convallatoxin by digoxin immune Fab is unlikely to provide therapeutic benefit.

Anti‐Tumor Effects of Cardiac Glycosides on Human Lung Cancer Cells and Lung Tumorspheres

“…Regardless of the source, CT exerts cytotoxic effects on a number of cancer cell lines (Felth et al, ; Levrier et al, ; Yang et al, ; Schneider et al, ) but its effects in cancer‐stem like cells is not known. In humans, the serum concentration of CT required to produce symptoms is unknown but in animal models the toxic levels of CT has been reported to be in the range of 18–180 μM (Fink et al, ). Therefore our report that CT can target cells with increased stemness properties at nanomolar concentrations (50–100) makes this drug an interesting candidate for the treatment of chemoresistant tumors.…”

Comprehensive review of cardiovascular toxicity of drugs and related agents

“…In addition, a placebo‐controlled clinical study confirmed their effectiveness against yellow oleander intoxication . However, the digoxin‐specific antibody fragments do not seem to be useful for the intoxication with glycosides from the lily‐of‐the‐valley ( Convallaria majalis ) . Limited shelf‐life and their higher cost make these antidotes available only at special cardiology, or toxicology centers.…”

“…316 However, the digoxin-specific antibody fragments do not seem to be useful for the intoxication with glycosides from the lily-of-the-valley (Convallaria majalis). 317 Limited shelf-life and their higher cost make these antidotes available only at special cardiology, or toxicology centers. Correction of possible hypokalemia should be performed as soon as possible and ventricular dysrhythmias may require additional symptomatic treatment.…”

The Molecular Basis of Toxins’ Interactions with Intracellular Signaling via Discrete Portals

“…The toxicity (LD 50 ) of cardiac glycoside is about 10 mg /kg upon i.p. injection in mice, [151]. Development of clinically relevant cardiac glycosides could be helped by systematic evaluation of the large family of cardiac glycosides and synthetic analogs available to date.…”