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PubMedDate not supplied

Poisoning due to ingestion of Veratrum viride (false hellebore).

We present six cases of poisoning due to ingestion of Veratrum viride (false hellebore) and review the physiology of veratrum alkaloids. Significant bradycardia and hypotension can occur after intoxication by veratrum plants, which grow widely in swampy areas of the eastern and western United States. Nausea and vomiting also occur typically after ingestion. Atropine is the mainstay of therapy, but pressors may be required to maintain blood pressure. Cases of veratrum poisoning have not been widely reported in the emergency medicine literature.

Administration, Oral↗
PubMed2003

Development of an enzyme-linked immunosorbent assay for the veratrum plant teratogens: cyclopamine and jervine.

Veratrum californicum was responsible for large losses of sheep grazing high mountain ranges in central Idaho in the 1950s. Veratrum induces various birth defects including the cyclopic-type craniofacial defect (monkey-faced lambs) that is specifically induced in lambs after pregnant ewes grazed the plant on the 14th day of gestation. The steroidal alkaloids cyclopamine (1) and jervine (2) were isolated from Veratrum and shown to be primarily responsible for the malformations. Cyclopamine (1) and jervine (2) are potent teratogens that inhibit Sonic hedgehog (Shh) signaling during gastrulation-stage embryonic development, producing cyclopia and holoprosencephaly. Although losses to the sheep industry from Veratrum are now relatively infrequent, occasional incidents of toxicoses and craniofacial malformations are still reported in sheep and other species. However, the benefits to biomedical research using cyclopamine (1) as a tool to study human diseases have greatly expanded. A competitive inhibition enzyme-linked immunosorbent assay (ELISA) to detect and measure cyclopamine (1) and jervine (2) was developed using polyclonal antibodies produced in ewes. The limits of detection of the assay were 90.0 and 22.7 pg for cyclopamine (1) and jervine (2), respectively. This assay was used for the detection and measurement of cyclopamine (1) spiked into sheep blood. The simple extraction-ELISA methods developed in this study demonstrate the potential of using these techniques for the rapid screening of biological samples to detect the presence and concentration of cyclopamine (1) and jervine (2) and will be beneficial to pharmacological studies and livestock diagnostics.

Abnormalities, Drug-Induced↗
PubMed2006

Veratrum poisoning.

Several species of the Veratrum genus are associated with toxicity in humans and animals. The principal toxins are steroid alkaloids; some have a modified steroid template, whereas others differ in their esterified acid moieties. These alkaloids act by increasing the permeability of the sodium channels of nerve cells, causing them to fire continuously. Increased stimulation, associated with the vagal nerve results in a reflex that causes the triad of responses known as the Bezold-Jarisch reflex: hypotension, bradycardia and apnoea. Clinically, various Veratrum extracts were marketed for clinical use as antihypertensive drugs, but because of their narrow therapeutic index were withdrawn from the market. Following the ingestion of Veratrum alkaloids, expected signs and symptoms include vomiting and abdominal pain, followed by cardiovascular effects such as bradycardia, hypotension and cardiac conduction abnormalities and death. Similar symptoms arise in other mammalian species ingesting these alkaloids; teratogenic effects may occur to the fetuses of animals that have grazed on Veratrum californicum. Treatment consists of supportive care, with an emphasis on haemodynamic stability with fluid replacement, atropine and vasopressors. The onset of symptoms occurs between 30 minutes and 4 hours, and the duration of the illness can range from 1 to 10 days; however, with prompt supportive care, patients typically make a full recovery within 24 hours.

Adult↗
PubMed1980

Analysis of the sensitizing effect of veratrum alkaloids to potassium on frog muscle.

1. The sensitizing effect of veratrum alkaloids to potassium is not specific. Reducing the concentration of chloride in Ringer's solution, or treating the muscle with nicotine in a concentration close to threshold after pretreatment with subliminal concentration of cevadine result in a marked mechanical response of the muscle. However, cevadine does not alter the sensitivity of the muscle to caffeine. On the basis of these observations it has been suggested that veratrum alkaloids sensitize the muscle membrane essentially to depolarizing processes. 2. Cevadine, 0.01 mM, fails to depolarize the muscle membrane but increases the depolarizing effect of 10 mM potassium. The depolarizing effect of a reduction of the concentration of chloride from 120 mM to 30 mM is also increased in cevadine pretreated muscle. Cevadine pretreatment increases the depolarizing effect of nicotine, too. 3. The above sensitizing effects are unanimously Na-dependent. Accordingly there is no mechanical response and increased depolarization in muscles equilibrated in sodium-free (choline) Ringer's solution before the cevadine treatment. 4. On the basis of the present data it is suggested that the membrane, when sensitized by veratrum alkaloids, can be triggered by different depolarizing processes and the depolarization increases as the result of increased Na permeability. The increased depolarization at the threshold level becomes sufficient for the automatic regenerative processes of the action potential to develop which activate the contractile elements. However, the mechanical response is a prolonged contraction rather than a contracture, its long period being the result of a very slow repolarization caused by the well-known inhibitory effect of veratrum alkaloids on Na inactivation.

Animals↗
PubMed1994

[Veratrum alkaloids. I].

Alkaloids represent an important group of therapeutically significant secondary metabolites. The plants of the genus Veratrum contain alkaloids with an antihypertensive effect. Also the genera Schoenocaulon and Zygadenus are sources of veratrum alkaloids. The present paper presents a survey of isolated alkaloids from the underground and aerial parts of 17 species of the genus Veratrum. The alkaloids occur as glycosides, aglycones or in the form of esters with various acids. In conformity with the IUPAC regulations for the nomenclature of steroids, Veratrum alkaloids were divided into 7 groups. The present paper lists the compounds of the first two groups, i.e. (1) alkaloids of the jervanine and veratranine types (I-XXIII), and (2) alkaloids with the cevanine skeleton (XXIV-XXXV). The individual compounds are characterized by their physico-chemical constants (melting point, optical rotation).

Veratrum Alkaloids↗
PubMed2006

Development of in vitro techniques for the important medicinal plant Veratrum californicum.

VERATRUM CALIFORNICUM (Liliaceae) is an important monocotyledonous medicinal plant which is the only source of the anticancer compound cyclopamine. An IN VITRO culture system for somatic embryogenesis and green plant regeneration of VERATRUM CALIFORNICUM was developed. Embryogenic calli were induced from mature embryos on induction medium. Five basal media supplemented with different growth regulators were evaluated for embryogenic callus induction, modified MS medium with 4 mg/L picloram showing the best result for embryogenic callus production. Fine suspension cell lines were established by employing friable embryogenic calli as starting material and AA medium and L2 medium as culture media. The suspension cell lines cultured in AA medium with 4 mg/L NAA appeared to be fresh yellow and fast growing. The suspension cells were cryopreserved successfully and recovered at a high rate. Green plants were regenerated from embryogenic calli maintained on solid medium with 73 % regeneration ability (green plants/100 calli) in 27-month-old culture. The IN VITRO plantlets contained the steroid alkaloids cyclopamine and veratramine. This IN VITRO system will form the basis for metabolic engineering of VERATRUM cells in the context of biotechnological production of pharmaceutically important secondary metabolites. DMSO:dimethyl sulfoxide fw:fresh weight NAA:naphthaleneacetic acid 2,4-D:2,4-dichlorophenoxyacetic acid picloram:4-amino-3,5,6-trichloro-2-pyridinecarboxylic acid dicamba:3,6-dichloro-2-methoxybenzoic acid.

Cryopreservation↗
PubMed2005

The importance of nitrogen and carbohydrate storage for plant growth of the alpine herb Veratrum album.

We examined whether nitrogen (N) and carbohydrates reserves allow Veratrum album, an alpine forb, to start spring growth earlier than the neighbouring vegetation and to survive unpredictable disturbances resulting in loss of above-ground biomass. * Seasonal dynamics of plant reserves, soil N availability and vegetation growth were monitored. Veratrum album shoots were experimentally removed when carbohydrate reserves were at a seasonal minimum and the subsequent changes in biomass and reserves were compared with those in control plants. Reserves did not give V. album a competitive advantage in spring; however, they did function as a buffer against the impact of calamities. Shoot removal resulted in significantly lower root dry weight, higher N concentration in rhizome and roots and lower starch concentrations in rhizome and roots but no plant mortality was observed. Veratrum album used stored N reserves to supplement N uptake and establish high leaf N concentrations, which facilitated a rapid refilling of depleted carbohydrate reserves. The primary function of N reserves appears to be to allow V. album to complete the growing cycle in as short a period as possible, thus minimizing exposure to above-ground risks.

Carbohydrate Metabolism↗
PubMed1985

[Acute dietary poisoning by white hellebore (Veratrum album L.). Clinical and analytical data. A propos of 5 cases].

Five cases of acute accidental poisoning with White Hellebore are reported. All cases occurred several minutes after the ingestion of home-made gentian wine. The clinical signs were nausea, vomiting, abdominal pain, hypotension and bradycardia. The initial ECG showed sinus bradycardia in 4 cases. In one patient, complete atrioventricular block with an ectopic atrial bradycardia and an intermittent idioventricular rhythm was recorded. Symptomatic treatment and/or atropine led to recovery within a few hours. These symptoms suggested poisoning with a veratrum alkaloid. The White Hellebore (Veratrum Album L.) and the Yellow Gentian (Gentiana Lutea L.) often grow side by side in the fields; it is easy to confuse the two plants before they flower if one is not a botanist. Each gentian wine was analysed by thin layer chromatography and chemical ionisation spectrometry. All the wines contained Veratrum alkaloids.

Abdomen↗
PubMed1981

[Veratrum album poisoning (author's transl)].

Ingestion of plant material rarely gives rise to manifest clinical intoxication. This is due to the relatively low toxicity of most of the poisonous plants of Central Europe. Veratrum album is an important exception on account of its highly toxic alkaloids. Seven cases of overt intoxication from veratrum album have been reported to the Austrian Poison Information Centre during the past 5 years. On the basis of these case reports toxicological and clinical aspects of this rare form of poisoning are discussed.

Adult↗
PubMed1980

Stimulation of cardiac receptors with veratrum alkaloids inhibits ADH secretion.

The purpose of this study was to determine whether cardiac receptors that are stimulated by veratrum alkaloids exert an inhibitory influence on the secretion of vasopressin (ADH). In six chloralose-anesthetized dogs, injection of cryptenamine (2 microgram/kg) into the circumflex coronary artery resulted in a significant (P < 0.05) fall in arterial pressure (-45 +/- 5 mmHg). Despite this hypotension and the presence of intact arterial baroreflexes, there was no change in plasma ADH (measured in the superior vena cava). In eight dogs with sinoaortic baroreceptor denervation, hemorrhage of 10 ml/kg decreased arterial pressure 20 +/- 5 mmHg (P < 0.05) and increased plasma ADH from 14 +/- 5 to 38 +/- 13 microU/ml (P < 0.05). Intracoronary injection of cryptenamine (1 microgram/kg) decreased plasma ADH to 23 +/- 7 microU/ml during the 5 min immediately after cryptenamine injection and to 16 +/- 4 microU/ml 20 min after injection. In eight dogs with sinoaortic denervation, hemorrhage and injection of vehicle resulted in a progressive increase in plasma ADH over the same time period. Vagotomy abolished the inhibitory response to cryptenamine injection. These data show that stimulation of cardiac receptors with vagal afferents by intracoronary injection of a veratrum alkaloid inhibits ADH secretion. Activation of these receptors can prevent arterial baroreflex-induced increases in ADH.

Afferent Pathways↗
PubMed1993

Intoxication from Veratrum album.

Two new cases of Veratrum poisoning are described. Clinical symptoms occurred quickly, within 30 min. Vomiting, a fall in blood pressure and bradycardia were observed. The outcome was favourable in both cases, producing a cure without sequellae. Examination of the literature showed that such cases are nearly always accidental, resulting from the difficulty in distinguishing Veratrum album and Gentiana.

Blood Pressure↗
PubMed1990

Early embryonic death in lambs induced by Veratrum californicum.

Both field and laboratory observations have suggested the possibility of embryonic death from 14th day ingestion of Veratrum californicum by pregnant sheep. An experiment was conducted to tabulate the incidence of embryonic death from 14th day ingestion of high doses of plant material. Six of eight ewes so dosed were non-pregnant at term (75%), compared to none in controls, and were, therefore, believed to have experienced embryonic death from the plant ingestion. Results suggest that ingestion of plant material could account for many open ewes at lambing time in ranching operations where Veratrum has been ingested in early gestation.

Animals↗
PubMed1995

Time course and inhibition of stavaroside K, veratramine and cevine-induced hemolysis by other pregnane glycosides and Veratrum alkaloids.

Stavaroside K, veratramine and cevine induce hemolysis, whereas 7 other pregnane stavarosides and 8 Veratrum alkaloids are not hemolytic. On the other hand, erythrocytes pretreated or incubated with low concentrations of stavarosides D-F or with the 8 other Veratrum alkaloids were resistant to hemolysis induced by authentic saponin, stavaroside K, cevine or veratramine. Veratridine, zygadenine and angeloylzygadenine (the known Na-Channel-Gate toxins) revealed the most potent reduction of hemolytic activity.

Cevanes↗
PubMed2006

Useful plants of dermatology. VIII. The false hellebore (Veratrum californicum).

Plants have and continue to provide medicine with an abundance of pharmacologically interesting and useful chemicals. In recent years, cyclopamine, a steroidal alkaloid isolated from Veratrum californicum, has been instrumental in dissecting the sonic hedgehog pathway. This brief report outlines cyclopamine's discovery with discussion of its potential application to clinical dermatology.

Animals↗
PubMed1960

Interactions of veratrum alkaloids, procaine, and calcium with monolayers of stearic acid and their implications for pharmacological action.

The interactions of veratridine, cevadine, veracevine, and veratramine with monolayers of stearic acid show marked differences. Veratridine and cevadine, at concentrations that are known from potential, ionic flux, and other measurements to affect living membranes, react strongly with the film and appear to cause an "interfacial dissolution" whereby both the alkaloid and the stearate leave the surface. Veracevine at the same concentration does not interact with the film. The veratramine reaction is weak, much like that of the local anesthetic procaine. The veratridine and cevadine effects are antagonized by 10(-3)M Ca(++), low pH, and 3.7 and 7.4 x 10(-3)M procaine. These differences among the veratrum alkaloids and the antagonisms parallel effects observed in living systems. Such parallelism suggests that similar physical interactions are involved in the stearate film and in natural membranes.

Anesthetics, Local↗
PubMed2000

Prolonged cardiotoxicity from poison lilly (Veratrum viride).

A 51-y-o otherwise healthy male presented to the emergency department 45 min after ingesting a soup made with boiled "leeks". Physical examination was significant for severe vomiting depressed mental status, and sluggishly reactive 2-3 mm pupils. Heart rate was 30 bpm and bp was 40/p mmHg requiring atropine and fluid resuscitation. After 60 min substernal chest pressure was noted and an ECG showed new V2-V6 ST segment depression. Recurrent hypotension required the use ofa dopamine infusion. At this time, the regional poison control center botanist identified a sample of the ingested material as Veratrum viride. The patient improved slowly over the next 24 hours, although bradycardia and heart block persisted for approximately 48 hours.

Antihypertensive Agents↗