Role of anthraquinones in Cassia occidentalis induced hepato-myo-encephalopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: The different plant parts of Cassia occidentalis Linn, (CO) such as root, leaves, seeds and pods have traditionally been used in multifarious medicines for the treatment of dysentery, diarrhea, constipation, fever, eczema, cancer and venereal diseases. MATERIALS AND METHODS: A systematic search of literature has been done in books and scientific databases like Science Direct, Pubmed, Google Scholar and Scopus etc. These sources were used to compile, analyze and review the information regarding the phytochemistry, toxicology and mechanism of toxicity of CO. The various references on this subject are cited in our review ranging from 1956 to 2019. RESULTS: Unintentional exposure of CO causes serious pathological condition in children, known as hepato-myo-encephalopathy (HME). The toxicity after CO consumption is associated with the presence of anthraquinones (AQs), a class of secondary plant metabolites. These AQs at high concentrations are known to cause detrimental effects on essential vital organs such as liver, kidney, spleen, brain, muscle and reproductive organs. The animal studies in rodent models as well as clinical investigations have clearly revealed that CO toxicity is associated with enhanced hepatotoxicity serum markers (ALT, AST, and LDH) and presence of necrotic lesions in liver. Furthermore, CO also causes vacuolization in muscle tissue and increases the level of CPK which is a prominent muscle damage marker. Apart from these target organs, CO consumption also causes neuronal damage via disturbing the levels of different proteins such as (GFAP and b-tubulin III). The mechanistic studies show that AQs present in CO have the potential to disturb the cellular homeostasis via binding to DNA, increasing the production ROS and showing inhibitory effects on essential enzymes etc. Therefore, AQs have been observed to be the primary culprit agents contributing to the toxicity of CO in children and animals. CONCLUSION: Despite its therapeutic potential, CO consumption can be detrimental if consumed in high amounts. A thorough analysis of literature reveals that AQs are the primary factors contributing to toxicity of CO seeds. Exposure to CO seeds causes HME, which is a serious life threatening condition for the malnourished children from lower strata. Multiple mechanisms are involved in the CO induced HME in patients. Lack of appropriate diagnostic measures and a poor understanding of the CO toxicity mechanism in humans and animals complicate the clinical management of CO poisoning subjects. Therefore, development of point of care diagnostic kits shall help in early diagnosis & suitable management of CO poisoning.

Rumen and Serum Metabolomes in Response to Endophyte-Infected Tall Fescue Seed and Isoflavone Supplementation in Beef Steers.

Fescue toxicosis impacts beef cattle production via reductions in weight gain and muscle development. Isoflavone supplementation has displayed potential for mitigating these effects. The objective of the current study was to evaluate isoflavone supplementation with fescue seed consumption on rumen and serum metabolomes. Angus steers (n = 36) were allocated randomly in a 2 × 2 factorial arrangement of treatments including endophyte-infected (E+) or endophyte-free (E-) tall fescue seed, with (P+) or without (P-) isoflavones. Steers were provided a basal diet with fescue seed for 21 days, while isoflavones were orally administered daily. Following the trial, blood and rumen fluid were collected for metabolite analysis. Metabolites were extracted and then analyzed by UPLC-MS. The MAVEN program was implemented to identify metabolites for MetaboAnalyst 4.0 and SAS 9.4 statistical analysis. Seven differentially abundant metabolites were identified in serum by isoflavone treatment, and eleven metabolites in the rumen due to seed type (p < 0.05). Pathways affected by treatments were related to amino acid and nucleic acid metabolism in both rumen fluid and serum (p < 0.05). Therefore, metabolism was altered by fescue seed in the rumen; however, isoflavones altered metabolism systemically to potentially mitigate detrimental effects of seed and improve animal performance.

Cerbera odollam: A Case Report of Attempted Suicide by Pong Pong.

Cerbera odollam, commonly referred to as the "suicide tree" or "pong pong," produces highly toxic seeds that are used for suicidal and homicidal purposes. It is important that western physicians be aware of the symptoms associated with these seeds and how to diagnose and treat them.

Concentrations of various forms of vitamin B6 in ginkgo seed poisoning.

A 2-year-old girl required medical attention for a sudden onset of repetitive tonic-clonic convulsions after ingesting 20-30 ginkgo seeds. Concentrations of the major forms of circulating vitamin B6, pyridoxal-5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid, as well as the known ginkgo seed toxin 4'-O-methylpyridoxine (MPN) were measured in the serum and cerebrospinal fluid (CSF). PLP is an active form of vitamin B6 and necessary for γ-aminobutyric acid (GABA) production. High MPN concentrations were observed in both the serum and CSF. As the PLP to PL ratio was markedly decreased in serum and CSF examinations, we suspected the ratio to be important in GABA production. This case report provides novel information on the metabolism of vitamin B6 in humans as a result of ginkgo seed poisoning.

Cardiac arrhythmias, electrolyte abnormalities and serum cardiac glycoside concentrations in yellow oleander (Cascabela thevetia) poisoning - a prospective study.

BACKGROUND: Consumption of yellow oleander (Cascabela thevetia) is a popular method of intentional self-harm in South India. OBJECTIVES: The objectives of this study were to identify the cardiac arrhythmias and electrolyte abnormalities in yellow oleander poisoning and to identify the association between electrolyte abnormalities, cardiac glycoside concentrations at admission and the severity of cardiotoxicity. This study was also designed to identify clinical and biochemical parameters at presentation which predict serious arrhythmias and determinants of mortality. MATERIALS AND METHODS: This was a prospective study among 192 patients who attended our Emergency department after consuming yellow oleander seeds. Patients were monitored with serial ECGs. Serious cardiac arrhythmias included sinus bradycardia <40/min, sinus arrest/exit block, second or third degree AV block, atrial tachyarrhythmias and ventricular tachyarrhythmias. Serum sodium, potassium, magnesium, total calcium and cardiac glycoside concentrations were measured at presentation for all 192 patients. Serial estimation of cardiac glycoside concentration was done in 43 patients who presented within 24 hours of consuming at least five seeds. RESULTS: At presentation, 46 patients had serious arrhythmias and on follow-up, 11 developed new-onset serious arrhythmia. Sinus bradycardia (27%) was the most common arrhythmia followed by second-degree AV block (17%); multiple arrhythmias were observed in 18%. Digoxin effect in ECG correlated significantly with hyperkalemia. Mortality rate was 5%. Serum sodium, total calcium and magnesium levels did not correlate with cardiotoxicity. Cardiac glycoside concentration was of relatively modest clinical utility to discriminate patients with serious dysrhythmias (AUC: 0.719, 95% CI: 0.63-0.81). Prolonged PR interval and digoxin effect in ECG were significantly associated with an increased likelihood of serious dysrhythmias. Increase in 0.4 number of seed intake increased the odds of mortality by 1.5 times when all other independent variables were kept constant. CONCLUSION: Cardiac glycoside concentration at the time of presentation predicted the development of new-onset serious arrhythmias. Although serum potassium correlated significantly with cardiac glycoside concentration at admission and overall serious dysrhythmias, it did not predict the development of new-onset serious arrhythmia. On the whole, serious dysrhythmias were significantly associated with higher number of seeds ingested, hypotension at admission, PR interval prolongation, presence of digoxin effect in ECG, hyperkalemia and higher cardiac glycoside concentration. The independent determinants of mortality were larger number of seeds ingested and hypotension at admission. Cardiac glycoside concentration and hyperkalemia failed to be independent markers of serious dysrhythmias as well as mortality.

Acute myocardial infarction in yellow oleander poisoning.

Self-harm by consuming yellow oleander seeds has become more frequent in South Asian countries, especially Sri Lanka and in southern parts of India. Yellow oleander poisoning usually presents with gastrointestinal, cardiovascular, and neurological manifestations as well as electrolyte abnormalities. Cardiac effects can manifest as nearly any type of dysrhythmia and sudden death with very few premonitory signs. To our knowledge yellow oleander poisoning related acute myocardial infarction has not yet been reported. We report a 37-year-old man with yellow oleander poisoning who had normal sinus rhythm at presentation but within few hours developed acute ST-segment myocardial infarction.

Poisoning after Ingestion of Spartium junceum Seeds: Dose-Dependent Effects in Three Boys.

BACKGROUND: Spanish broom (Spartium junceum L.) is an ornamental, medicinal, and potentially poisonous plant. CASE REPORT: Three children, aged 5-6 years, were accidentally poisoned from ingesting a variable number of seeds of Spanish broom. This plant contains several quinolizidine alkaloids as cytisine, which act as an agonist of nicotinic acetylcholine receptors. The potential danger varies, depending on the dose. After having ingested one to two seeds, one of the boys was asymptomatic. A second boy ingested four to five seeds and presented some digestive problems with favorable clinical evolution. A third boy ingested seven to eight seeds, and presented with digestive and neurologic symptoms, as well as minor metabolic acidosis. In this case there was vomiting with remains of the seeds. He responded well to a gastric lavage and activated charcoal. He was discharged 24 h post ingestion. The intake within one to eight seeds was accompanied by moderate symptoms, with good response to treatment. Children poisoned by plants with nicotine-like symptomatology usually fully recover, but some fatal cases have been reported. Prevention is always a key aspect to consider so as to reduce the risk of poisoning. There is a lack of legislative measures, based on lists provided by experts, to regulate real or potentially poisonous plants in children's areas. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case serves as an example of accidental plant poisoning. For emergency physicians, it is usually complicated to identify the specific plant involved, so initial treatment often starts with basic measures (airway, breathing, and circulation).

Acute abrin poisoning treated with continuous renal replacement therapy and hemoperfusion successfully: A case report.

RATIONALE: Abrin is a highly toxic protein obtained from the seeds of Abrus precatorius, but poisoning due to ingestion of A precatorius is extremely rare in China. PATIENT CONCERNS: A 16-year-old girl, perfectly healthy before, was admitted to the department of gastroenterology owing to intentional ingestion of 10 crushed A precatorius seeds, with multiple episodes of somnolent and anxious mental status, vomiting, abdominal pain, diarrhea, hematochezia, and hematuria. DIAGNOSIS: Acute abrin poisoning. INTERVENTIONS: We immediately took effective measures including gastric lavage, purgation, gastric acid suppression by proton pump inhibitor (PPI), liver protection, hemostasis, blood volume and electrolytes resuscitation, continuous renal replacement therapy (CRRT), and hemoperfusion (HP). OUTCOMES: Her unwell mental status was improved to the point at which she became conscious and relaxed. The symptoms of vomiting, abdominal pain, diarrhea, hematochezia, and hematuria disappeared gradually. The girl eventually made an excellent recovery with no complications at her 3-month follow-up. LESSONS: The combination of CRRT and HP is an efficient measure in the treatment of abrin poisoning for which there is no specific antidote. This is the first reported case of an abrin poisoning patient successfully treated by CRRT plus HP. Our experience will be useful to other physicians in managing patients of acute abrin poisoning in the future.

Acute intoxication due to Wisteria floribunda seed in seven young children.

BACKGROUND: Wisteria floribunda is a vine commonly found in Korea, Japan, and the USA. The objective of this observational study was to assess the toxicity of W. floribunda seeds in young children. METHODS: Of 28 children in a kindergarten who participated in a field trip, seven ingested W. floribunda seeds: six half of the seed and one a whole seed. These seven children were admitted to the Gachon University Gil Medical Center in Incheon, Korea. RESULTS: All of the children had vomiting within 4 h of ingesting the W. floribunda seed; the child who ingested a whole seed began to vomit 2 h after ingestion. By 5 h after ingestion, they all complained of abdominal pain and one child was lethargic. Leukocytosis was observed in all of the children. Abdominal pain and vomiting subsided in all of the children within 2 days after admission. The average duration of hospitalization was 3.1 days. CONCLUSIONS: W. floribunda seed ingestion induced gastrointestinal and neurologic symptoms in these young children. Given that the onset of vomiting was earlier in the child who ingested a whole seed than in the children who had ingested only a half, the amount of ingested seeds may be associated with the severity of the symptoms. Ingestion of half a raw W. floribunda seed can cause gastrointestinal symptoms in young children and even result in hospitalization.

Case report: a rare case of attempted homicide with Gloriosa superba seeds.

BACKGROUND: Gloriosa superba, well known as the glory lily or superb lily, is a tropical climbing plant that features an exotic red flower. The plant is poisonous because of high concentrations of colchicine in all parts of the plant. It is commercially grown for use in Ayurveda medicine and as a cash crop for extracting colchicine in India and Africa. It is a wild plant in Sri Lanka and commercial cultivation is rare. Accidental and suicidal poisonings with Gloriosa tubers are well known and reported. There are no case reports of poisoning by Gloriosa seeds in Sri Lanka. Google and PubMed searches showed no reported cases of poisoning with seeds or their use with homicidal intent in other parts of the world. CASE PRESENTATION: A 27-year-old man was brought to hospital with profuse vomiting and diarrhea after drinking coriander tea, which is a common traditional treatment for common cold. The family members suspected poisoning by Gloriosa because they had seeds at home and the victim's sister-in-law who had made the herbal tea went missing from home. They were able to identify Gloriosa seeds, which looked similar to coriander, in the pot. The patient developed shock and respiratory distress and needed ventilation and intensive care. He also developed mild renal impairment, and thrombocytopenia. He developed massive generalized alopecia while recovering from acute illness. Full recovery was achieved after 15 days of hospital care. CONCLUSIONS: There are many poisonous plants in Asian countries. This case highlights the possibility of accidental or intentional use of Gloriosa seeds or its extracts to cause potentially fatal poisoning. It would be difficult to identify Gloriosa as the cause of poisoning without any background information because of multiple complications that can mimic a systemic infection. This case is a good example of the use of plants as biological weapons.

Hypoglycin A Content in Blood and Urine Discriminates Horses with Atypical Myopathy from Clinically Normal Horses Grazing on the Same Pasture.

Hypoglycin A (HGA) in seeds of Acer spp. is suspected to cause seasonal pasture myopathy in North America and equine atypical myopathy (AM) in Europe, fatal diseases in horses on pasture. In previous studies, this suspicion was substantiated by the correlation of seed HGA content with the concentrations of toxic metabolites in urine and serum (MCPA-conjugates) of affected horses. However, seed sampling was conducted after rather than during an outbreak of the disease. The aim of this study was to further confirm the causality between HGA occurrence and disease outbreak by seed sampling during an outbreak and the determination of i) HGA in seeds and of ii) HGA and MCPA-conjugates in urine and serum of diseased horses. Furthermore, cograzing healthy horses, which were present on AM affected pastures, were also investigated. AM-pastures in Germany were visited to identify seeds of Acer pseudoplatanus and serum (n = 8) as well as urine (n = 6) from a total of 16 diseased horses were analyzed for amino acid composition by LC-ESI-MS/MS, with a special focus on the content of HGA. Additionally, the content of its toxic metabolite was measured in its conjugated form in body fluids (UPLC-MS/MS). The seeds contained 1.7-319.8 µg HGA/g seed. The content of HGA in serum of affected horses ranged from 387.8-8493.8 µg/L (controls < 10 µg/L), and in urine from 143.8-926.4 µg/L (controls < 10 µg/L), respectively. Healthy cograzing horses on AM-pastures showed higher serum (108.8 ± 83.76 µg/L) and urine concentrations (26.9 ± 7.39 µg/L) compared to control horses, but lower concentrations compared to diseased horses. The range of MCPA-carnitine and creatinine concentrations found in diseased horses in serum and urine were 0.17-0.65 mmol/L (controls < 0.01), and 0.34-2.05 µmol/mmoL (controls < 0.001), respectively. MCPA-glycine levels in urine of cograzing horses were higher compared to controls. Thus, the causal link between HGA intoxication and disease outbreak could be further substantiated, and the early detection of HGA in cograzing horses, which are clinically normal, might be a promising step in prophylaxis.

Abrin poisoning in an 18-month-old child.

BACKGROUND: When discussing known poisons and their clinical consequences, few physicians are aware of the deadly poison abrin. The common symptoms of abrin toxicity include nausea, vomiting, abdominal pain, and diarrhea with or without bloody stool. However, with an estimated fatal human dose of less than 1 microgram/kg, death due to complications such as liver failure, renal failure, and cerebral edema are possible. CASE REPORT: An 18-month-old male presented to the emergency department with an abrupt onset of fever, vomiting, diarrhea, and dehydration. The parents had assumed the child was suffering from a severe gastroenteritis until they noticed 3 consecutive diapers containing colorful seeds that were identified by poison control as belonging to the Abrus precatorius plant. The child's gastrointestinal symptoms were consistent with reported cases of abrin poisoning, but the patient also had an isolated and significantly elevated alkaline phosphatase, with testing unable to reveal the responsible pathological process. CONCLUSIONS: To reduce morbidity and possible mortality, parents and pediatricians alike should be conscious of the danger the Abrus precatorius seed poses to the pediatric population. Children are at a greater risk of ingesting these seeds due to their colorful appearance, and the consequences could be fatal. Through this case report we hope to raise public awareness regarding this toxin. This includes the management of known cases, as well as the possibility of encountering an isolated elevated alkaline phosphatase level as a laboratory finding if ingestion occurs.

Severe cyanide poisoning from an alternative medicine treatment with amygdalin and apricot kernels in a 4-year-old child.

BACKGROUND: The use of complementary and alternative medicine (CAM) is widespread in children with cancer and is poorly regulated. PATIENTS AND METHODS: Case report. RESULTS: We describe a case of severe cyanide poisoning arising from CAM use. A severely agitated, encephalopathic, unresponsive 4-year-old boy (initial Glasgow Coma Scale of 3) with a history of metastatic ependymoma was brought to our emergency department by ambulance services. Initial blood gas analysis demonstrated severe metabolic/lactic acidosis. On detailed questioning of the parents, the use of CAM including intravenous and oral "vitamin B 17" (amygdalin) and oral apricot kernel was reported. After administering sodium thiosulfate, rapid improvement in his medical condition with complete recovery without need for further intensive care treatment was seen. Serum cyanide level was markedly elevated. CONCLUSIONS: Cyanide poisoning can be the cause of severe encephalopathy in children receiving CAM treatment with substances containing cyanogenic glycosides.

Oxidant-induced damage to equine erythrocytes from exposure to Pistacia atlantica, Pistacia terebinthus, and Pistacia chinensis.

Two horses were referred for methemoglobinemia and hemolytic anemia following 5 acute deaths in their herd from an unidentified toxin source. Horses have a greater risk than other mammalian species of developing methemoglobinemia and hemolytic anemia following ingestion of oxidizing toxins, due to deficiencies in the mechanisms that protect against oxidative damage in erythrocytes. Their susceptibility to oxidative erythrocyte damage is evident in the numerous cases of red maple (Acer rubrum) toxicosis. The suspected toxins causing A. rubrum toxicosis are tannic acid, gallic acid, and a metabolite of gallic acid, pyrogallol. These compounds can be found in a variety of plants, posing a risk to equine health. In order to quickly identify toxin sources, 2 rapid in vitro assays were developed to screen plant extracts for the ability to induce methemoglobin formation or cause hemolysis in healthy equine donor erythrocytes. The plant extract screening focused on 3 species of the genus Pistacia: P. atlantica, P. terebinthus, and P. chinensis, which were located in the horse pasture. Extracts of the seeds and leaves of each species induced methemoglobin formation and resulted in hemolysis, with seed extracts having greater potency. The in vitro assays used in the current study provide a useful diagnostic method for the rapid identification of oxidizing agents from unidentified sources. There is no effective treatment for oxidative erythrocyte damage in horses, making rapid identification and removal of the source essential for the prevention of poisoning.