Plant toxin poisoning–a disguised diagnosis?

Abstract

Many very poisonous plants grow outdoors, or can be purchased at the store, and some popular wild edible plants can easily be confused with a toxic ‘twin’ plant. Diagnosis of plant poisoning can, however, be challenging. Would yew (Taxus baccata) intoxication have crossed your mind, when finding a person unconscious with signs of acute heart failure, just a few hours after last observed physically fit? We present a challenging analytical investigation, of what turned out to be a fatal yew poisoning. Further, we will present our development of a new comprehensive screening method for plant toxins in blood, using UHPLC-QTOF-MS (ultra-high performance liquid chromatography quadrupole time-of-flight/mass spectrometry). Thanks to excellent interdisciplinary cooperation and new advanced technology, we have identified a death caused by yew toxins. No substances were initially detected by our extensive routine chromatographic toxicological analysis in postmortem blood and urine, including high-resolution mass spectrometry (UHPLC-QTOF-MS) with a repertoire of approximately 850 substances in blood. However, when comparing MS findings in the postmortem blood sample against a large library of approximately 3000 toxicologically relevant compounds, the substance 3,5-dimethoxyphenol (3,5-DMP) was found. 3,5-DMP is a non-toxic marker of yew poisoning. Since the toxic substances in yew, taxine B and taxine A, were not available for purchase as pure reference materials, we produced and analyzed extracts of needles, bark and twigs of three types of yew from our own gardens. The identities of taxine B and taxine A in the deceased's blood and urine sample were then confirmed by comparison with the results for these extracts. The concentration of 3,5-DMP in postmortem blood was found to be 0.7 μmol/L (0.11 mg/L), using purchased reference material for 3,5-DMP. The breakthrough experienced in this yew case spurred us on to develop a new advanced UHPLC-QTOF-MS method for screening of a broad range of plant toxins in blood samples. For many toxins, we will also be able to perform quantitative analysis. A seldom cause of death that could easily have been overlooked was revealed, due to perseverance and some luck. Yew has a high content of cardiotoxic alkaloids, which can lead to death within few hours after ingestion. Taxine B mediates cardiotoxicity by blocking calcium channels, and to some extent sodium channels, in heart muscle cells, and this can induce refractory ventricular fibrillation. In order to improve diagnostics, knowledge and national cooperation on plant and mushroom poisonings in Norway, we are developing a new advanced analytical screening method, and we have also established a nationwide and tightly cooperating ‘Competence group on plant and mushroom toxins’. The group is composed of medical pharmacologists, toxicologists, an anesthesiologist, chemists, veterinarians, and botanists. Plant toxin poisoning, like the presented fatality caused by yew, is a diagnosis that can easily be missed. We are developing an advanced screening method (UHPLC-QTOF-MS) for a large selection of plant toxins in blood, to improve diagnostics and knowledge on such poisonings.