piperidines and Plant-Poisoning

Rhabdomyolysis (R) is a complex condition involving the rapid dissolution of damaged or injured skeletal muscle. This leads to the direct release of intracellular components, including myoglobin, creatine kinase, aldolase, and lactate dehydrogenase, as well as electrolytes, into the bloodstream and extracellular space. Clinically, R shows a triad of symptoms: myalgia, limb weakness, and myoglobinuria without hematuria, while myoglobin has been recognized as playing a part in the development of acute kidney injury. Coturnism is a relatively rare disease, mostly found in the European countries bordering the Mediterranean Sea, characterized by acute R. It follows the consumption of Coturnix coturnix, a species of quails common in Europe, that have ingested the toxic substances (and especially coniine) present in the herbaceous plant called hemlock (Conium maculatum). Coniine may be lethal at a dose of 150 mg but it has neurotoxic effects at smaller doses, with acute R and acute kidney injury. Freezing and cooking the meat does not inactivate the alkaloids present in the birds' flesh and digestive tract. The clinical course of coturnism includes neurotoxicosis, tremor, vomiting, muscle paralysis, respiratory paralysis/failure, R and acute kidney injury. In appropriate geographical and temporal settings, it should be considered when diagnosing patients with acute R. The genetic, biochemical and epidemiological characteristics of coturnism are not yet fully known, while we wait reliable data from experimental studies.

Topics: Acute Kidney Injury; Alkaloids; Animals; Foodborne Diseases; Humans; Muscle, Skeletal; Piperidines; Plant Poisoning; Quail; Rhabdomyolysis

The aim of this paper is to highlight the symptomatology in three Conium maculatum intoxication incidents, one of which was fatal. A number of studies were reviewed in order to update and summarize the relevant literature on the incidence, sociodemographic variables, method of poisoning, pathophysiology, diagnosis, variables associated with survival and fatality, management, and treatment of C. maculatum intoxication as well as the biosynthesis and biological effects of poison hemlock alkaloids. Results show that hemlock poisoning is relatively rare, although incidence varies in different regions, despite its worldwide distribution. Hemlock poisoning is more common in European and especially Mediterranean countries. The majority of the patients are adult males over 38 years of age. The clinical course of hemlock poisoning includes neurotoxicosis, tremor, vomiting, muscle paralysis, respiratory paralysis/failure, rhabdomyolysis, and acute renal failure. The therapeutic management focuses on absorption reduction, close observation for complications, and supportive therapy (especially for respiration). Acute occurrence is severe and life-threatening, but the survival rate is high if treatment is provided promptly. Recovery is rapid, generally taking only a few days.

Topics: Accidents; Aged; Alkaloids; Animals; Antidotes; Antiemetics; Charcoal; Chromatography, Liquid; Conium; Gas Chromatography-Mass Spectrometry; Gastric Lavage; Humans; Livestock; Male; Molecular Structure; Phytotherapy; Piperidines; Plant Poisoning; Respiratory Paralysis; Rhabdomyolysis; Suicide

Quinolizidine and piperidine alkaloid teratogens from Lupinus, Conium, and Nicotiana genera have been identified as causes of birth defects in livestock induced by poisonous plants. Many defects now known to be related to poisonous plant ingestion were once thought to have a genetic origin. This supposition delayed diagnosis, reporting, and understanding of such birth defects, because breeders and producers feared the news would make it difficult to sell breeding stock. Defects caused by quinolizidine and piperidine teratogens include cleft palate and contracture-type skeletal defects such as arthrogryposis, scoliosis, torticollis, and kyphosis. Teratogens have been identified, differences in susceptibility to teratogenic compounds among livestock species have been elucidated, periods of gestation when specific types of birth defects occur have been determined, and information about mechanism of action has been developed.

Topics: Alkaloids; Animals; Animals, Domestic; Congenital Abnormalities; Nicotiana; Piperidines; Plant Poisoning; Plants, Toxic

Topics: Alkaloids; Child, Preschool; Hemlock; Humans; Male; Piperidines; Plant Poisoning; Plants, Toxic; Pyridines

Two anaesthetized sheep were intoxicated with epoxyscillirosidin, the main cardio-active bufadienolide, extracted from Homeria pallida (Natal yellow tulp). The epoxyscillirosidin was injected intravenously as a bolus of 50 micrograms/kg, followed 30 min later by a continuous infusion in a normal saline drip (0.9% NaCl) at 25 micrograms/kg/h. In addition, another two conscious sheep were poisoned by intraruminal dosing of 1,25 g/kg of dried H. pallida plant material. Electrocardiograms, heart and respiratory rates and venous-acid-base levels were recorded prior to and at approximately 30-60 min intervals during the course of the experiment. Additional recordings were made when animals showed signs of intoxication. R56865 (Janssen Pharmaceutica, Pty Ltd), a novel Ca++ antagonist, was administered at the first distinct signs of cardiac disturbances in the sheep given epoxyscillirosidin and after development of tachycardia and dyspnoea in those that received plant material. Activated charcoal was drenched at 3 g/kg to both sheep that received H. pallida about 1 h after the initial administration of R56865. All H. pallida sheep and one of the epoxyscillirosidin sheep survived. The signs of intoxication with H. pallida, namely groaning and tachypnoea, abated within minutes of treatment with R56865, but returned c. 30 min later in both animals. The treatment apparently had little effect on heart rate and EKG changes. One of the epoxyscillirosidin sheep was treated while exhibiting paroxysmal ventricular tachycardia. Although a transient improvement in conduction disturbance was recorded, the animal died soon afterwards. The results of this study indicate that the in vivo response of R56865 against induced bufadienolide cardiac disturbance in sheep is not as evident as that observed with R56865 against similar cardiac disturbance in vitro. The potential use of R56865 together with activated charcoal is discussed.

Topics: Animals; Benzothiazoles; Bufanolides; Calcium Channel Blockers; Cholenes; In Vitro Techniques; Piperidines; Plant Extracts; Plant Poisoning; Sheep; Sheep Diseases; Thiazoles; Toxins, Biological

We report the clinical and histological findings in patients with acute renal failure caused by the ingestion of wildfowl who had eaten hemlock buds. Neurotoxic effects were accompanied by rhabdomyolysis, myoglobinuria, and acute tubular necrosis. Histological studies showed diffuse degeneration of the tubular epithelium. Immunohistological studies demonstrated the presence of myoglobin and actin in renal tubular cells.

Topics: Acute Kidney Injury; Alkaloids; Animals; Birds; Humans; Kidney; Kidney Tubular Necrosis, Acute; Piperidines; Plant Poisoning

Cattle in two herds developed signs of bloating, increased salivation and lacrimation, depression, respiratory distress, ataxia, and death after ingestion of hay that contained large amounts of poison hemlock (Conium maculatum). Twenty of 30 Angus cows and calves were affected in the first herd (2 died). In the second herd, 5 of 30 Holstein heifers were affected (1 died). The Conium alkaloids, coniine and gamma-coniceine, were quantified in the hay, the plants from the responsible hayfield, and the urine of affected animals.

Topics: Alkaloids; Animal Feed; Animals; Cattle; Cattle Diseases; Chromatography, Gas; Female; Gastrointestinal Contents; Mass Spectrometry; Medicago sativa; Piperidines; Plant Poisoning; Plants, Toxic; Rumen

In the past, hemlock poisoning was only known for its neurotoxic effects; quite recently non-neurological features, consisting of rhabdomyolysis and acute renal failure, have been also described. Here we report our experience with these clinical findings, which we frequently observe in accidental hemlock poisoning. Between 1972 and 1990 we studied 18 patients: 17 of them were poisoned by conline (an alkaloid of Conium maculatim) in Apulia (Italy), and one by cicutoxin (the active principle of water hemlock) in New Mexico (USA). In the non-rapidly-fatal cases we tested myoglobinuria, serum muscle enzymes, and renal function. In the patients with acute renal failure we performed microscopical examination of kidney specimens; immunohistochemistry was carried out to identify myoglobin and actin in tubules. Coniine was detected in urine, serum, or tissues. Neurological features were present in all of our cases: coniine had a curare-like effect on the neuromuscular junction, whereas cicutoxin was convulsant on the central nervous system. In addition rhabdomyolysis was noted in the 17 subjects poisoned by coniine. Acute renal failure was observed in five patients; it was confirmed by histological evidence of tubular necrosis with intratubular deposition of myoglobin and actin released by rhabdomyolysis. Our cases seem to be the first with histopathologically proven acute tubular necrosis in coniine intoxication. In conclusion, in hemlock poisoning neurotoxic manifestations may be accompanied by rhabdomyolysis and acute tubular necrosis; increased awareness of these clinical features is recommended in order to improve the diagnostic and therapeutic procedure.

Topics: Adult; Aged; Alkaloids; Alkynes; Diynes; Fatty Alcohols; Female; Humans; Kidney Tubular Necrosis, Acute; Male; Middle Aged; Nervous System Diseases; Piperidines; Plant Poisoning; Rhabdomyolysis

Three piperidine alkaloid containing plants, Conium maculatum (poison-hemlock), Nicotiana glauca (tree tobacco) and Lupinus formosus (lunara lupine), induced multiple congenital contractures (MCC) and palatoschisis in goat kids when their dams were gavaged with the plant during gestation days 30-60. The skeletal abnormalities included fixed extension or flexure of the carpal, tarsal, and fetlock joints, scoliosis, lordosis, torticollis and rib cage abnormalities. Clinical signs of toxicity included those reported in sheep, cattle and pigs--ataxia, incoordination, muscular weakness, prostration and death. One quinolizidine alkaloid containing plant, Lupinus caudatus (tailcup lupine), on the other hand, which is also known to cause MCC in cows, caused only slight signs of toxicity in pregnant goats and no teratogenic effects in their offspring.

Topics: Abnormalities, Multiple; Alkaloids; Anabasine; Animals; Bone and Bones; Cleft Palate; Female; Goat Diseases; Goats; Nicotiana; Piperidines; Plant Extracts; Plant Poisoning; Plants, Toxic; Pregnancy; Pyridines; Teratogens

Topics: Alkaloids; Animals; Female; Male; Piperidines; Plant Poisoning; Plants, Toxic; Rabbits

A young adult male was found dead in a field. No cause of death was apparent at autopsy, and the only positive toxicological finding was the presence of a nicotine-like alkaloid isolated from the liver. Anabasine, the major, highly toxic alkaloid of the shrub, Nicotiana glauca (tree tobacco) was subsequently identified in all body specimens examined using gas chromatography/mass spectrometry. Concentrations of anabasine in blood, urine and other body organs are reported.

Topics: Adult; Alkaloids; Anabasine; Gas Chromatography-Mass Spectrometry; Humans; Male; Nicotiana; Piperidines; Plant Poisoning; Plants, Toxic

Topics: Alkaloids; Animals; Congenital Abnormalities; Female; Piperidines; Plant Poisoning; Pregnancy; Swine; Swine Diseases

Cleft palates were induced in newborn pigs of gilts fed Conium maculatum seed or plant during gestation days 30 through 45. Twelve of 23 newborn pigs born to 3 gilts given Utah-grown C maculatum seed and 9 of 12 newborn pigs born to a single gilt given the fresh Utah spring-growth C maculatum plant had cleft palates. The cleft palates ranged from a unilateral cleft, involving only 1 side of the palate, to a full bilateral cleft. Brachygnathia was also observed in some of these newborn pigs with cleft palate. Other malformations were not observed. Chemical analysis of seed and plant samples indicated that gamma-coniceine was the responsible teratogenic alkaloid. A daily dose of plant or seed that provided greater than or equal to 1.07 mg of gamma-coniceine/kg of body weight fed to gilts during the 30th through the 45th day of pregnancy resulted in teratogenic effects.

Topics: Alkaloids; Animals; Animals, Newborn; Chromatography, Gas; Cleft Palate; Female; Piperidines; Plant Poisoning; Plants, Toxic; Pregnancy; Pregnancy Complications; Pyridines; Seeds; Swine; Swine Diseases

Collections of Nicotiana glauca containing from 0.45-1.14 mg anabasine per gram dry weight of plant induced moderate - severe toxic signs in pregnant ewes and teratogenic effects in their offspring when the ewes were given single daily doses of the plant that provided from 1.66 - 3.42 mg anabasine per kg body weight. Toxic signs included excess salivation, irregular gait, wobbling while walking or standing, recumbency and death. Teratogenic effects occurred in offspring from animals fed those doses the 30th - 60th day of gestation. Terata expression included limb defects such as a fixed excessive carpal flexure with or without lateral or medial rotation of fore or rear limbs, lordosis, irregular shaped head or cleft palate.

Topics: Abnormalities, Drug-Induced; Alkaloids; Anabasine; Animals; Cattle; Cattle Diseases; Female; Gas Chromatography-Mass Spectrometry; Limb Deformities, Congenital; Male; Nicotiana; Piperidines; Plant Poisoning; Plants, Toxic; Pregnancy; Sheep; Sheep Diseases; Swine; Swine Diseases

Nicotiana glauca consumption by pregnant cows or sows produced arthrogryposis and other congenital deformities in their offspring. The plant material administered contained 0.11% anabasine, the suspect teratogen. But concentration varied among various plant parts; woody material was very low but leaves and bark were high. The anabasine was identified by mass spectral fragmentation analysis.

Topics: Anabasine; Animals; Arthrogryposis; Cattle; Cattle Diseases; Congenital Abnormalities; Female; Piperidines; Plant Poisoning; Plants, Toxic; Pregnancy; Swine; Swine Diseases; Teratogens

Topics: Abnormalities, Drug-Induced; Alkaloids; Animals; Animals, Newborn; Cattle; Chromatography, Gas; Female; Mass Spectrometry; Piperidines; Plant Poisoning; Plants; Pregnancy; Sheep

Topics: Abnormalities, Drug-Induced; Animals; Cats; Cattle; Chromosome Aberrations; Chromosome Disorders; Disease Models, Animal; Dogs; Ehlers-Danlos Syndrome; Freemartinism; Genetic Diseases, Inborn; Genetic Linkage; Heart Defects, Congenital; Humans; Immunologic Deficiency Syndromes; Karyotyping; Leukocytes; Mercury Poisoning; Mink; Mosaicism; Nicotiana; Piperidines; Plant Extracts; Plant Poisoning; Plants, Medicinal; Plants, Toxic; Sheep; Swine; Veratrum