Analytical confirmation of Xanthium strumarium poisoning in cattle.

Xanthium strumarium, commonly referred to as "cocklebur," rarely causes poisoning in cattle. When mature, this robust, annual weed bears numerous oval, brownish, spiny burs. Only the seeds in the burs and young seedlings (cotyledonary leaves) contain the toxic principle, carboxyatractyloside. In the Frankfort district of the Free State Province of South Africa, a herd of 150 Bonsmara cows were allowed to graze on the banks of a small river, where mature cocklebur was growing. Four cows died while grazing in this relatively small area. Clinical signs ranged from recumbency, apparent blindness, and hypersensitivity to convulsive seizures. During necropsy, burs completely matted with ingesta were located in the rumen content. The most distinctive microscopic lesions were severe, bridging centrilobular to midzonal hepatocyte necrosis and hemorrhage. Ultrastructurally, periacinar hepatocytes were necrotic, and novel electron-dense cytoplasmic needle-like crystals were observed, often in close association with peroxisomes. Carboxyatractyloside concentrations were determined using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Carboxyatractyloside was present in rumen contents at 2.5 mg/kg; in burs removed from the rumen at 0.17 mg/kg; in liver at 66 ng/g, and was below the limit of quantitation in the kidney sample, estimated at approximately 0.8 ng/g. Based on the presence of the plants on the riverbank, the history of exposure, the clinical findings, the presence of burs in the rumen, and the microscopic and ultrastructural lesions, X. strumarium poisoning in the herd of cattle was confirmed and was supported by LC-HRMS.

[Atractylis gummifera: from poisoning to the analytic methods]. / Atractylis gummifera : de l'intoxication aux méthodes analytiques.

Atractylis L gummifera is a plant that causes every year serious and often deadly poisonings. In Morocco, 153 cases of poisoning have been recorded between January 1980 and June 1995 by the Moroccan Antipoison Centre. The ignorance by the clinicians, the fast evolution and the frequency of these poisonings are the origin of diagnosis problems. The solution of those problems is to detect atractyloside and carboxyatractyloside in the biologic liquids. Since several decades, some toxicological analytical methods were established in view of an assay. The aim of our paper is to describe the poisoning by this plant and to review the methods of toxicological analysis used from the colorimetric technique until the news recent chromatographic methods.

Hepatorenal injury induced by cutaneous application of Atractylis gummifera L.

INTRODUCTION: In Mediterranean countries, intoxication by Atractylis gummifera L. is frequent and characterized principally by hepatorenal injury, often fatal. Its toxicity after a cutaneous application is unknown. We report a case of poisoning by A. gummifera L. induced by repeated cutaneous application. CASE REPORT: A 30-month-old boy was admitted in our pediatric intensive care unit in coma (Glasgow Coma Scale 8). Investigations showed hepatic cellular injury, cholestasis, decreased prothrombin level, and increased creatinine. History from the parents revealed repeated and occlusive cutaneous application of A. gummifera L. on a skin burn. Qualitative analysis of urine confirmed the diagnosis of A. gummifera poisoning. The child was discharged after 16 days of hospitalization with residual renal insufficiency. DISCUSSION: Poisoning by A. gummifera L. after cutaneous application has not previously been reported in the literature. The prevention of this poisoning, particularly frequent in Mediterranean countries, is mainly based on the education of the public concerning the dangers of this plant.

Identification of atractyloside by LC-ESI-MS in alleged herbal poisonings.

An LC-MS screening method was developed to detect the presence of atractyloside (ATR), the toxic principle of a commonly used medicinal plant in South Africa, Callilepis laureola, in biological matrices such as body fluids and human viscera.

Carboxyatractyloside poisoning in humans.

OBJECTIVE: Cocklebur (Xanthium strumarium) is an herbaceous annual plant with worldwide distribution. The seeds contain the glycoside carboxyatractyloside, which is highly toxic to animals. We describe nine cases of carboxyatractyloside poisoning in humans which, to our knowledge, has not previously been reported. The clinical, laboratory and histopathological findings and our therapeutic approach are also discussed. SUBJECTS AND METHODS: The patients presented with acute onset abdominal pain, nausea and vomiting, drowsiness, palpitations, sweating and dyspnoea. Three of them developed convulsions followed by loss of consciousness and death. RESULTS: Laboratory findings showed raised liver enzymes, indicating severe hepatocellular damage. BUN and creatinine levels were raised, especially in the fatal cases who also displayed findings of consumption coagulopathy. CPK-MB values indicative of myocardial injury were also raised, especially in the fatal cases. Three of the patients died within 48 hours of ingesting carboxyatractyloside. Post-mortem histopathology of the liver confirmed centrilobular hepatic necrosis and renal proximal tubular necrosis, secondary changes owing to increased permeability and microvascular haemorrhage in the cerebrum and cerebellum, and leucocytic infiltrates in the muscles and various organs including pancreas, lungs and myocardium. CONCLUSIONS: Carboxyatractyloside poisoning causes multiple organ dysfunction and can be fatal. Coagulation abnormalities, hyponatraemia, marked hypoglycaemia, icterus and hepatic and renal failure are signs of a poor prognosis. No antidote is available and supportive therapy is the mainstay of treatment.

Gas chromatographic-mass spectrometric confirmation of atractyloside in a patient poisoned with Callilepis laureola.

The South African traditional remedy Impila (Callilepis laureola) contains the mitochondrial toxin atractyloside. The plant is sold widely and continues to lead to fatalities in patients. We describe, for the first time, a simple GC-MS procedure for the identification of atractyloside, which we have applied to the gastric washing from a poisoned patient and to extracts of Impila tuber.

The biochemistry and toxicity of atractyloside: a review.

Atractyloside poisoning is an infrequent but often fatal form of herbal poisoning, which occurs worldwide but especially in Africa and the Mediterranean regions. The primary mechanism of atractyloside poisoning is known to be inhibition of the mitochondrial ADP transporter. Poisoning in humans may present with either acute hepatic or renal pathology and it is possible that there is a second, different mechanism of toxicity to the hepatocyte. Atractyloside in large amounts gives rise to massive necrosis, but in vitro studies have shown that at lower doses cells progress to apoptosis. Simple methods for the detection of atractyloside poisoning are at present restricted to thin-layer chromatography in urine and are useful only in the case of severe poisoning. Immunoassays, high-performance liquid chromatography, nuclear magnetic resonance, and a recently developed high-performance liquid chromatography/mass spectrometry method have yet to be applied to clinical diagnoses. There is at present no treatment, but a fuller understanding of the mechanisms of toxicity may lead to the application of a number of compounds that are effective in vitro.

Detection of poisoning by Impila (Callilepis laureola) in a mother and child.

Poisoning with impila (Callilepis laureola) is a recurring phenomenon in South Africa. Cases of poisoning with other plants which contain atractyloside also occur in Europe and the Americas. Since poisoning leads to rapid death from renal and/or hepatic failure, it is suspected that many cases are undiagnosed; this is especially so in South Africa, where patients may die without reaching hospital and do not often admit to ingestion of a traditional remedy. We have developed a thin layer chromatographic method for the detection of impila constituents in urine. We describe the clinical symptoms and the application of the screening method to diagnosis in the case of a mother and child, who both showed symptoms of impila poisoning; the mother died but the child survived. This method is rapid and may be used for the definitive diagnosis in cases of poisoning with atractyloside-containing plants.

Cocklebur poisoning in cattle.

Cocklebur poisoning occurred in a herd of cattle in Oklahoma during the month of July. The poisonous dicotyledonary stage of cocklebur plant growth usually occurs during the early spring in Oklahoma. In this instance, dicotyledonary sprouts were in a lowland pasture adjacent to a river. Sprouting and growth occurred after receding water and hot dry weather had created favorable conditions for germination. The diagnosis was made on the basis of the finding of the dicotyledonary stage of plant growth and evidence of the plants having been grazed, as well as the clinical signs, gross necropsy findings, and histopathologic findings in the affected cattle.

Toxicologic study of carboxyatractyloside (active principle in cocklebur--Xanthium strumarium) in rats treated with enzyme inducers and inhibitors and glutathione precursor and depletor.

Male rats (10 rats/group) were treated with phenobarbital (PB), phenylbutazone (PBZ), stanozolol (3 inducers of cytochrome P450-dependent enzymes), piperonyl butoxide (PBO; a P450 inhibitor), cobaltous chloride (CoCl2; an inhibitor of hemoprotein synthesis), 5,6-benzoflavone (BNF; an inducer of cytochrome P448 dependent enzymes), cysteine [CYS; a glutathione (GSH) precursor], or ethyl maleate (EM; a GSH depletor). The rats were then given a calculated LD50 dosage (13.5 mg/kg of body weight) of carboxyatractyloside (CAT) intraperitoneally. Clinical signs of toxicosis, duration of illness, lethality, gross lesions, and hepatic and renal histopathologic lesions were recorded. Seemingly, (i) CAT toxicosis has independent lethal and cytotoxic components (PBZ decreased lethality and cytotoxicity; CoCl2 decreased cytotoxicity but not lethality; BNF decreased duration of illness, and perhaps lethality, but not cytotoxicity); (ii) CAT cytotoxicity could be partly due to an active metabolite formed by de novo-synthesized, P450-/P448-independent hemoprotein (PBZ and CoCl2 had anticytotoxic effects, but PB, stanozolol, PBO, and BNF did not); (iii) CAT detoxification may occur partly through a hemoprotein-independent, PBZ-inducible enzyme, and partly through a P448-dependent (BNF-inducible) enzyme; and (iv) CAT detoxification apparently is not P450 or GSH-dependent because PB, stanozolol, and CYS had no beneficial effects, and PBO, CoCl2, and EM did not enhance toxicosis. Metabolism of CAT may have a role in its cytotoxic and lethal effects.

Cocklebur (Xanthium strumarium, L. var. strumarium) intoxication in swine: review and redefinition of the toxic principle.

Cocklebur (Xanthium strumarium) fed to feeder pigs was associated with acute to subacute hepatotoxicosis. Cotyledonary seedings fed at 0.75% to 3% of body weight or ground bur fed at 20% to 30% of the ration caused acute depression, convulsions, and death. Principle gross lesions were marked serofibrinous ascites, edema of the gallbladder wall, and lobular accentuation of the liver. Acute to subacute centrilobular hepatic necrosis was present microscopically. The previously reported toxic principle, hydroquinone, was not recovered from the plant or bur of X. strumarium. Authentic hydroquinone administered orally failed to produce lesions typical of cocklebur intoxication but did produce marked hyperglycemia. Carboxyatractyloside recovered from the aqueous extract of X. strumarium and authentic carboxyatractyloside, when fed to pigs, caused signs and lesions typical of cocklebur intoxication. Marked hypoglycemia and elevated serum glutamic oxaloacetic transaminase and serum isocitric dehydrogenase concentrations occurred in pigs with acute hepatic necrosis that had received either cocklebur seedlings, ground bur or carboxyatractyloside.

[Poisoning by bird-line thistle (Astractylis gummifera L.) (author's transl)]. / L'intoxication par le charcon à glu (Atractylis gummifera l.).

The thistle grows in the dry areas of North-Africa and is rather common. The juice of the root is poisonous. Two toxic components have been isolated and their formulas specified. They induce liver necrosis, and block the ADP-ATP conversion. Prognosis is most often fatal, except in mild forms when symptomatic treatment is very early.

[Fulminating hepatitis caused by glue thistle (Atractylis glummifera-L.), poisoning. Anatomo-pathological study of 4 cases]. / Hépatite fulminante par intoxication due au chardon à glu (Atractylis gummifera-L). Etude anatomo-pathologique de 4 cas

The toxicity of the "glue thistle" is well known in Algeria. 10 children were involved in a case of collective poisoning. Only two survived. Histo-pathological studies were made in four cases, the clinical and histological picture being that of a fulminating hepatitis with major hepatocellular necrosis.