Veratrum Steroidal Alkaloid Toxicity Following Ingestion of Foraged Veratrum Parviflorum M Anwar 1, MW Turner 2, N Farrell 3, R Kleiman 4, WB Zomlefer 5, OM McDougal 2, BW Morgan 1 1Emory University School of Medicine, Atlanta, GA; 5Boise State University, Boise, ID; 3Rhode Island Hospital, Providence, RI; 4Wellstar Kennestone Hospital, Marietta, GA; 5University of Georgia, Athens, GA

BACKGROUND RESULTS DISCUSSION • Steroidal alkaloids are found in the Veratrum genus of • The specimen was identified as V. parviflorum by botanists • Steroidal alkaloids have previously been isolated and toxicity plants. at the University of Georgia . has been reported from many species of Veratrum plants. ¦ ¢ ¥ ¤ ¡ £ ¢ ¡ ¨ § • Their toxicity manifests as GI illness followed by a x10 7 1.0 • This is the first reported case of Veratrum toxicity from V. Bezold-Jarisch reflex: hypopnea, hypotension and 0.5

©¨ parviflorum with identified steroidal alkaloids. bradycardia. x10 7 1.0 • As far as we know, there is no previous study to characterize • Some Veratrum steroidal alkaloids are also teratogens 0.5 ¨

x10 7 the steroidal alkaloids in V. parviflorum . interfering with the hedgehog-2 signaling pathway which 1.0 causes cyclopsia and holoprosencephaly. 0.5

¨ • A prior study shows some cross reactivity between Veratrum x10 7 1.0 steroidal alkaloids and the digoxin assay but no digoxin CASE PRESENTATION 0.5

¨ immune fab binding.

x10 7 • A 27 year old man (patient 1) and his 25 year old wife 1.0 0.5

(patient 2) presented to the ED with nausea and 0 x10 7 f) vomiting after foraging and ingesting what they believed 1.0 to be wild leeks from the Appalachian Trail in Georgia, 0.5 10 USA. 0 20 30 40 50 Time [min] Figure 1. Total ion chromatograms (TIC) for (a) Patient 1 Plasma, (b) Patient 1 • The man and woman had BP 87/40, HR 53 and BP Serum, (c) Patient 2 Plasma, (d) Control serum, (e) plant extract spiked serum, and (f) V. parviflorum extract.

Intensity Intensity 88/40, HR 50 respectively after antiemetics and fluid 5 5 x10 x10 a) 398.3126 b) resuscitation. They were alert and awake throughout. 1.25 1.25 1.00 1.00 • ECGs showed sinus bradycardia. 0.75 0.75 0.50 0.50 268.1232

0.25 0.25 758.3882 • 10 vials of digoxin immune Fab were given due to 0.00 0.00 0 10 20 30 40 50 60Time [min] 100200300400500600700800900 m/z 6 6 x10 Figure 4. (L) A lamb head displaying the teratogenic effects of cyclopamine (Biins et al.). concern for cardiac glycoside toxicity with no response. x10 c) 410.3140 d) 3.00 3.00 (M) V. parviflorum. (R) Allium tricoccum - Ramps/wild leeks (UGA).

• Laboratory analysis showed undetectable digoxin 2.00 2.00 concentrations in both patients. 1.00 1.00 0.00 0.00 CONCLUSIONS 0 10 20 30 40 50 60Time [min] 100 200 300 400 500 600 700 800 900 m/z 5 5 x10 x10 • Their symptoms resolved 12 hours after arrival and they e) 412.3284 f) 2.00 2.00 • V. Parviflorum contains the steroidal alkaloids verazine, were discharged within 34 hours. 1.50 1.50 1.00 1.00 veratramine, cyclopamine, and veratridine. 0.50 0.50 141.9615 268.1230 658.3698 METHODS 0.00 0.00 0 10 20 30 40 50 60Time [min] 100 200 300 400 500 600 700 800 900 m/z • In patients presenting with cardiotoxicity after ingestion of 4 4 x10 x10 161.0996 g) 8.00 h) • We collected and analyzed the implicated fresh plant 2.50 wild plants in the Southeastern USA, consider V. parviflorum 2.00 6.00 1.50 toxicity. material and both patients’ serum/plasma. 4.00 1.00 674.4174 0.50 2.00

• We used liquid chromatography-mass spectroscopy and 0.00 0.00 0 10 20 30 40 50 60Time [min] 100 200 300 400 500 600 700 800 900 m/z REFERENCES high resolution electrospray ionization time of flight Figure 3. TICs and corresponding mass/spectrometry for Veratrum alkaloids Kang, et al. “Steroidal alkaloids from Veratrum nigrum enhance glucose uptake in skeletal muscle cells.” J. Nat. Prod. (2015) 78 : 803-810. tandem mass spectrometry to extract and characterize identified from the extracted biomass of V. parviflorum ; a-b: verazine (m/z Lui, et al. “Isolation, identification, and bioactivity of microbial metabolites of cyclopamine and its congeners.” Phytochemistry Letters. (2015) 12 : 203-208. 398.3125); c-d: veratramine (m/z 410.3141); e-f: cyclopamine (m/z 412.3285); Betchel LK, et al. Ingestion of false hellebore plants can cross-react with a digoxin clinical chemistry assay. Clinical Toxicology 2010;48:435- steroidal alkaloids from the foraged plant and patients’ 442 g-h: veratridine (m/z 674.4174). Grobosch T, et al. Accidental intoxication with Veratrum album. Journal of Analytical Toxicology 2008;32:768-73. serum. Froberg B, et al. Plant poisoning.Emerg Med Clin N Am 2007;25:375-433