A Zebrafish Embryo Model to Screen Potential Therapeutic Compounds in Sapindaceae Poisoning.

Hypoglycin A (HGA) and methylenecyclopropylglycine (MCPrG) are protoxins produced by Sapindaceae plants, particularly Acer pseudoplatanus, and are responsible for causing atypical myopathy (AM) in equids. These protoxins metabolise into toxic compounds, such as methylenecyclopropylacetyl-CoA (MCPA-CoA), which alters energy metabolism and induces severe rhabdomyolysis. Currently, no specific treatment exists for this poisoning, in vitro models fail to reproduce HGA's toxic effects on equine primary myoblasts, and mammalian models are impractical for large-scale drug screening. This study aimed to develop a zebrafish embryo model for screening therapeutic compounds against AM. Zebrafish embryos were exposed to various concentrations of HGA, MCPrG, and methylenecyclopropylacetate (MCPA) for 72 h. MCPrG did not induce toxicity, while HGA and MCPA showed median lethal concentration (LC50) values of 1.7 µM and 1 µM after 72 h, respectively. The highest levels of the conjugated metabolite MCPA-carnitine were detected 24 h after HGA exposure, and the acylcarnitines profile was highly increased 48 h post-exposure. Isovaleryl-/2- methylbutyrylcarnitine levels notably rose after 24 h, suggesting potential exposition biomarkers. Glycine and carnitine effectively reduced mortality, whereas riboflavin showed no protective effect. These findings suggest that the zebrafish embryo represents a valuable model for identifying therapeutic compounds for Sapindaceae poisoning.

[Epidemiological characteristics and toxicant type of acute poisoning cases in China, 2016-2022].

Objective: To analyze the acute poison epidemic and provide evidence for developing prevention and control strategies for acute poisoning. Methods: A retrospective analysis was conducted on acute poisoning cases collected from 2016 to 2022 in a health emergency information platform for acute poisoning accidents. The cases were grouped according to the distribution of poisoning occurrence time, geographic distribution, demographic distribution, types of toxicants, poisoning causes, and outcomes. Data were organized and analyzed using Excel 2016 and R 4.2.3. Results: A total of 95 754 acute poisoning cases were included in this study. The primary toxicants were pesticides, drugs, and industrial/household chemicals, accounting for 30.4%, 22.4%, and 20.4% of the total cases, respectively. Acute poisoning occurred throughout the year, with the highest frequency from June to August, accounting for 31.9%. The seasonal distribution varied among different types of toxicants. Except for plant poisoning, which showed a bimodal distribution, the other poisonings showed an unimodal distribution. There was a strong seasonality in fungal poisoning, which peaked in July. There was an obvious seasonality in animal poisoning, with a peak in August. The proportion of biological poisonings in the southwest region was higher than in other regions, including plants, animals, and fungi. There were more females than males, and their education level was mainly junior high school and below (35.2%). The main occupation was farmers (34.2%), and the main causes of poisoning were accidents and suicides. The case fatality rate of all poisoning cases was 1.24%. Pesticide poisoning was the most common type, and chlorfenapyr (11.68%), Diquat (7.23%), and paraquat (7.05%) ranked as the top three toxicants. Conclusions: The occurrence of acute poisoning has an obvious seasonal trend, and the toxicant spectrum of different regions and populations is different. A comprehensive poisoning surveillance system can provide a better understanding of the occurrence of poisonings, and facilitate the formulation of more scientifically precise poisoning prevention and control strategies.

Ricin intoxication by lethal dose of castor seeds ingestion: a case report.

INTRODUCTION: Ricin intoxication is a serious condition with symptoms ranging from mild gastroenteritis to fatal outcomes due to shock and multi-organ failure. Intoxication from the ingestion of castor seeds is uncommon. However, its diagnosis is crucial, particularly with a clear history of exposure to castor seeds, regardless of the route of exposure (enteral or parenteral). Prompt diagnosis is essential to monitor and manage the patient effectively and to prevent potentially fatal outcomes. We report a case where ingestion of castor seeds resulted in gastroenteritis severe enough to necessitate emergency medical care. CASE REPORT: We present the case of a 47-year-old Belgian woman of Moroccan descent, previously healthy who was admitted to the emergency department with symptoms of colicky abdominal pain, diarrhea, and vomiting following the ingestion of six castor beans. The patient was diagnosed with ricin intoxication, admitted for observation, and received symptomatic treatment. She was discharged home after a complete recovery three days later. CONCLUSION: Our report underscores the clinical manifestations, hemodynamic changes, laboratory findings, and treatment of intoxication due to castor seed ingestion. It contributes to the limited literature on castor seed poisoning in humans, with a specific focus on cases in Belgium. This report aims to raise awareness among clinicians about this condition and emphasizes the importance of a comprehensive history-taking to prevent misdiagnosis and malpractice.

Hair loss and endocrine dermatosis on horses raised in a Mimosa pudica var. unijuga-invaded area.

A Mimosa pudica var. unijuga-associated toxicity affecting horses occurred in Araguari, Triângulo Mineiro, Southeast Brazil. Affected horses had gradual hair loss of the mane and tail and endocrine dermatosis after grazing for three months during the dry season on a paddock invaded by the plant. The main histological lesions include compact ortho-keratotic hyperkeratosis and numerous flame follicles. Toxicological analysis by HPLC-UV demonstrated 0.8 mg/g of mimosine in the leaves.

A Feeding Trial to Investigate Strategies to Mitigate the Impacts of Pimelea Poisoning in Australian Cattle.

Pimelea poisoning of cattle causes distinct symptoms and frequently death, attributable to the toxin simplexin. Pimelea poisoning was induced via addition of ground Pimelea trichostachya plant to the daily feed in a three-month trial with Droughtmaster steers. The trial tested four potential mitigation treatments, namely, biochar, activated biochar, bentonite, and a bacterial inoculum, and incorporated negative and positive control groups. All treatments tested were unable to prevent the development of simplexin poisoning effects. However, steers consuming a bentonite adsorbent together with Pimelea showed lesser rates-of-decline for body weight (P < 0.05) and four hematological parameters (P < 0.02), compared to the positive control group fed Pimelea only. Microbiome analysis revealed that despite displaying poisoning symptoms, the rumen microbial populations of animals receiving Pimelea were very resilient, with dominant bacterial populations maintained over time. Unexpectedly, clinical edema developed in some animals up to 2 weeks after Pimelea dosing was ceased.

Nephrosis in cattle associated with consumption of Ludwigia peploides (Onagraceae).

This paper describes an outbreak of nephrosis in cattle associated with the consumption of Ludwigia peploides in Tucuman province, northwestern Argentina. Affected cows exhibited submandibular and chest edema, lethargy and ataxia, and eventually succumbed to these conditions. These animals were grazing in a floodable area severely invaded by this plant. The disease affected 7 out of a herd of 67 cows. Horses and goats grazing in the same location were not affected. The main gross and histological lesion corresponded to a severe nephrosis. The disease is similar to the poisoning by Ludwigia peruviana reported in Colombia.

Poor Survival Rate of Eastern Gray Kangaroos (Macropus giganteus) Affected by Chronic Phalaris Toxicity.

Chronic phalaris toxicity (CPT) is a neurological disease caused by animals ingesting toxins produced by early growth stages of Phalaris aquatica, a pasture plant introduced to the southeastern regions of Australia post colonization. Little is known about the clinical progression of CPT in wildlife, as incidents are sporadic and predominantly reported when animals are in the end stages of disease and in a poor welfare state. We studied a cohort of 35 eastern gray kangaroos (Macropus giganteus) affected by CPT to clarify clinical prognosis and survival rates. Kangaroos were captured in May, June, and July of 2022 at Plenty Gorge Parklands, Victoria, Australia. Each animal was radiotracked for 180 d, clinical progression and disease outcomes monitored twice a week. By the conclusion of the study, 24 animals had died (19 by euthanasia due to deterioration, five found dead). Ten animals survived, with two demonstrating a reduction in clinical signs and eight showing full resolution of clinical signs. One animal was disqualified from the study. The overall survival rate was 29.4% (95% confidence interval 17.5-49.5%). The survival duration of animals that died ranged from 5 to 133 d. There was no difference in survival rate based on sex (P=0.2), age class (P=0.49) or the month of capture (P=0.49). These results suggest that CPT is an important health and welfare concern for at-risk macropod populations, with high case-fatality rates and prolonged clinical durations. Further research to manage the disease via methods such as reducing Phalaris aquatica plant coverage and preventative treatments for animals is warranted to reduce disease incidences and improve disease outcomes in wildlife populations.

Poisonings in ruminants by Cenostigma pyramidale (Tul.) Gagnon & G.P.Lewis (Fabaceae): A mini-review of teratogenic potential and phytochemical evidence.

Teratogenic plants can be found in pastures in different parts of the world and represent a threat to the reproduction of ruminants. In the northeast region of Brazil, several studies have indicated that Cenostigma pyramidale (Tul.) Gagnon & G.P.Lewis is one of the main poisonous plants that causes reproductive problems in sheep and goats. In this context, the present study reviewed spontaneous and experimental poisonings reports by C. pyramidale in sheep and goats, as well as analyzing the phytochemical evidence related to this species. The scientific documents were retrieved from different databases and, after applying the selection criteria, a total of 16 articles published between 2000 and 2024 were included in this review. Cenostigma pyramidale causes embryonic loss, abortion, and congenital malformations in pregnant sheep and goats in the Brazilian semi-arid region. The main malformations observed in newborn animals are arthrogryposis, scoliosis, micrognathia, multiple skull deformities, cleft palate, and brachygnathism. Many secondary metabolites have already been isolated from C. pyramidale, however, to date, no evidence has been found regarding the possible teratogenic compounds that occur in this plant. From this perspective, new phytochemical studies are necessary to help unravel the mechanisms of action of embryotoxic agents from C. pyramidale.

Some phytotoxins causing reproductive alterations in ruminants.

The presence of phytotoxins in plants constitutes a health risk for herbivores, particularly on ruminants who accidently consume them. Among the adverse effects produced by these are reproductive alterations, represented by abortion, infertility, and morphological alterations in neonates, which are frequently attributed to other causes. While in some cases the plants that contain such metabolites are known, other times they are not, leading to alterations that are difficult to treat considering that their toxicodynamics are unknown. The objective of this documentary research is to provide information on how metabolites such as phytoestrogens, L-mimosine, labdane diterpenoids - isocupressic acid, quinolizidine alkaloids and piperidine swainsonine, anabasine, coniine and associated alkaloids, among others, exert their action in the animal organism and the effects they produce.

Solanum glaucophyllum intoxication in goats: Case study.

Solanum glaucophyllum is a toxic plant with calcinogenic effect that causes enzootic calcinosis (EC) characterized by soft tissue metastatic mineralization mainly in cattle and rarely sheep, buffaloes, pigs, horses, and goats. We describe an outbreak of EC in a herd of 64 goats due to S. glaucophyllum consumption. Thirty-four goats were affected exhibiting hirsutism, stiffening, kyphosis and emaciation. Twelve goats died. Grossly, tissue mineralization was observed in the aorta and carotid arteries, lungs, and heart. Lesions were characterized by multiple rough white plaques, and hardened tissues with loss of elasticity. Microscopically, multisystemic mineralization was observed in aorta and carotid arteries, heart, lung, abomasum, intestine, spleen, lymph nodes, kidney, spleen, and meninges, characterized by extensive granular basophilic deposits of tunica media and/or intima of blood vessels; confirmed as calcium salt deposits with Von Kossa stain. We conclude that ingestion of S. glaucophyllum can cause EC in goats. Though EC is rare in goats under some conditions such as heavy drought and abundant S. glaucophyllum exposure disease can develop.

Unveiling the Dark Side of Datura in Pediatric Poisoning With Insights From Jordanian Experience : A Retrospective Clinical Study.

OBJECTIVES: Datura stramonium , jimsonweed, is a toxic plant with hallucinogenic properties. Although there are many studies on Datura poisoning, none reported cases in Jordan. This study offers a comprehensive review on D. stramonium ingestion, covering its epidemiology, clinical presentation, and treatment. We aimed to provide better understanding of the factors for Datura ingestion, identify prevention and management strategies, and address research challenges. METHODS: This study adopted a retrospective review design to evaluate the cases of Datura poisoning in Al Karak, province of Jordan during the spring of 2022. Data collected from medical records, toxicology databases, and consultation records were analyzed using descriptive statistics. RESULTS: The common symptoms of Datura poisoning included agitation, mydriasis, and tachycardia. The management approaches comprised supportive care, administration of Diazepam for agitation, and, in some cases, neostigmine to counteract anticholinergic effects. CONCLUSIONS: Understanding the risks associated with D. stramonium poisoning and implementing effective prevention and management strategies are crucial. This study highlights the importance of recognizing Datura poisoning as a potential diagnosis in children presenting with unexplained anticholinergic symptoms or agitation to the emergency room.

Japanese Yew (Taxus) poisoning of wild ungulates in Utah during the winter of 2022-2023.

Taxus is a genus of coniferous shrubs and trees, commonly known as the yews, in the family Taxaceae. All species of yew contain taxine alkaloids, which are ascribed as the toxic principles. Anecdotally, free ranging ruminants such as antelope, deer, elk, and moose have been regarded as tolerant to yew. Herein several cases of intoxication of deer, elk, and moose by yew from the state of Utah in the winter of 2022-2023 are documented. Ingestion of yew was documented by three means among the poisoned cervids; plant fragments consistent with yew were visually observed in the rumen contents, chemical analysis, and subsequent detection of the taxines from rumen and liver contents, and identification of exact sequence variants identified as Taxus species from DNA metabarcoding. Undoubtedly, the record snowfall in Utah during the winter of 2022-2023 contributed to these poisonings.

Lisosomal storage disease caused by ingestion of Astragalus spp in llamas: an emergent concern.

Lysosomal storage diseases are inherited or acquired disorders characterized by dysfunctional lysosomes that lead to intracytoplasmic accumulation of undegraded substrates, causing impaired cellular function and death. Many acquired lysosomal storage diseases are produced by toxic plants, which have indolizidine alkaloids, including swainsonine, that inhibits lysosomal α-mannosidase and Golgi α-mannosidase II. Swainsonine-induced nervous disease associated with various plants has been reported, including species of the genus Astragalus, Sida, Oxitropis, Swainsona, and Ipomoea. Two species of Astragalus (i.e. Astragalus garbancillo and Astragalus punae) have been found to cause neurologic disease in llamas. In addition, A. garbancillo was also associated with malformations in the offspring, and possibly abortions and neonatal mortality in llamas. The diagnosis of Astragalus spp. intoxication is established based on clinical signs, microscopic and ultrastructural findings, lectin histochemistry, abundance of these plants in the grazing area and determination of swainsonine in plant specimens.

Pine needle abortions in cattle due to consumption of Pinus ponderosa in Argentina: Case reports.

Two outbreaks of pine needle abortions in cattle are here reported for the first time in Argentina. The cases occurred in Chubut and Neuquén provinces in the Patagonia region, causing 29.6% and 9% of abortions in each herd respectively. In both outbreaks, the dams were in the last third of gestation, and, due to a period of cold, snow and lack of available forage, they gained access to Pinus ponderosa and Pinus contorta forests. No pathological lesions, serological, molecular, or microbiological evidence of infectious causes were observed in any of the six fetuses analyzed. Microhistological analysis of feces confirmed higher presence of fragments of Pinus spp. needles in the diet of affected dams than in that of non-affected ones (12.2 vs 3.0%). Moreover, toxicological analysis showed higher tetrahydroagathic acid in the sera of affected dams than in that of non-affected ones (10.05 vs 2.81 ppm). In addition, this acid was detected in different fetal fluids (3.6-8.1 ppm) of the six fetuses analyzed. Interestingly, isocupressic acid was detected only in needles of P. ponderosa, and its content was lower than that found in other areas of the world (0.31 and 0.5% in Chubut and Neuquén respectively). These results confirm that the consumption of P. ponderosa by dams could have been the cause of these abortion outbreaks, a fact that should be considered as differential diagnosis in abortions of cattle, especially in silvopastoral systems of Argentina.

Acute death as a result of poisoning tropical (Bos taurus indicus) but not temperate (Bos taurus taurus) cattle after oral dosing with Lupinus leucophyllus (velvet lupine).

Due to climate change and increasing summer temperatures, tropical cattle may graze where temperate cattle have grazed, exposing tropical cattle to toxic plants they may be unfamiliar with. This work compared the toxicity of Lupinus leucophyllus (velvet lupine) in temperate and tropical cattle. Orally dosed velvet lupine in tropical cattle caused death. If producers opt to graze tropical cattle, additional care must be taken on rangelands where toxic lupines like velvet lupine grow.

Rhododendron poisoning in alpacas (Vicugna pacos) in Northern Germany.

Poisoning is often suspected to be the origin of disease in South American camelids (SACs) by owners, but only in a few cases this assumption can be confirmed. In small ruminants, rhododendron poisoning is a common emergency for livestock veterinarians. However, this condition has rarely been reported in SACs so far. This paper provides information regarding clinical findings, hematology, clinical chemistry, and treatment of four alpacas after presumed intake of rhododendron leaves including pathological findings of one of the animals. Rhododendron leaves contain grayanatoxins that lead to hyperpolarization of excitable cells. Clinical signs that were observed in the presented alpacas comprised: salivation, dehydration, decreased motility of compartment 1, uncoordinated regurgitation, and cardiac arrhythmia. Clinical chemistry revealed that rhododendron poisoning was associated with metabolic acidosis and azotaemia, hyponatremia and hyperkalemia. Most striking macroscopic and histopathological findings included gastric ulceration, and renal infarcts along with inflammatory changes. Leaves of Rhododendron spp. were identified in the forestomach content of this animal. Affected animals were treated symptomatically as there is no specific antidote in rhododendron poisoning. This included parenteral rehydration, treatment of metabolic acidosis (infusion of sodium bicarbonate solution), and oral administration of activated charcoal to bind potential toxins. In addition, antibiotic treatment might be necessary to prevent aspiration pneumonia in case of uncoordinated regurgitation. Of the four animals, the worst affected alpaca was euthanized, one had minimal signs and two responded to supportive care and recovered. In conclusion, rhododendron poisoning might be fatal for alpacas in individual cases and therefore rhododendron bushes should not be placed in the habitat of SACs.

Indigofera cryptantha-induced pigmenturia in cattle in South Africa.

Two field cases of reddish-black pigmenturia occurred where cattle grazed on an established Cenchrus ciliaris (blue buffalo grass) pasture in South Africa. The pasture was noticeably invaded by Indigofera cryptantha, which was heavily grazed. Apart from the discolored urine, no other clinical abnormalities were detected. Urinalysis revealed hemoglobinuria, proteinuria and an alkaline pH. When the animals were immediately removed from the infested pasture, they made an uneventful recovery. However, a bull died when one of the herds could not be removed from the I. cryptantha-infested pasture. Macroscopically, the kidneys were dark red in color and the urinary bladder contained the dark pigmented urine. Microscopically, the renal tubules contained eosinophilic, granular pigment casts in the lumen. In addition, many renal tubular epithelial cells were attenuated with granular cytoplasm and were detached from the basement membranes. Chemical analysis was performed on dried, milled plant material and two urine samples collected during the field investigations. Qualitative UPLC-UV-qTOF/MS analysis revealed the presence of indican (indoxyl-ß-glucoside) in the stems, leaves and pods of I. cryptantha and indoxyl sulfate was identified, and confirmed with an analytical standard, in the urine samples. It is proposed that following ingestion of I. cryptantha, indican will be hydrolysed in the liver to indoxyl and conjugated with sulfate. Indoxyl sulfate will then be excreted in relatively high concentrations in the urine. In the alkaline urine, two indoxyl molecules might dimerize to form leucoindigo with subsequent oxidation to indigo, thus, contributing to the dark pigmentation of the urine. It is also possible that indoxyl sulfate contributed to the renal failure and death of the bull. Although I. suffruticosa-induced hemoglobinuria has been described in Brazil, this is the first report of I. cryptantha-induced pigmenturia in cattle in South Africa.

Chronic phalaris toxicity in macropods is widespread and peaks in July in Victoria, Australia.

Phalaris aquatica is pasture species introduced into Australia during early European settlement. Consumption of the plant can cause the neurological condition chronic phalaris toxicity (CPT) in sheep and cattle. In recent years, there has been an increase in reports of CPT in macropods, which has raised concerns regarding its impacts on their welfare. Currently, little is known about the distribution or seasonal patterns of this disease in wildlife, information pivotal in assessing its potential risks. Between 2021 and 2022, we conducted a survey targeting government bodies, veterinary businesses and wildlife organisations to investigate the locations and time of occurrence of CPT in macropods in the state of Victoria, Australia. We received 13 survey responses, 12 verbal reports, a full record of investigated cases from a university veterinary school and cases from a wildlife rescue organisation. Over the period of 11 years, Victoria had 918 cases of CPT recorded in macropods from 36 local government areas, with cases concentrated centrally just north of the state capital of Melbourne and July (midwinter) being the month with the highest case count (n = 220). There was a significant positive correlation between case count and both the abundance of kangaroos (Macropus giganteus and Macropus fuliginosus) (P < 0.01) and the abundance of P. aquatica (P = 0.009), and a significant negative correlation between annual case count and average rainfall of March (P = 0.016) and April (P = 0.02). Understanding these relationships will assist land and wildlife managers in predicting the risk and magnitude of disease outbreaks of CPT each in Victoria.

Death of Socrates: a likely case of poison hemlock (Conium maculatum) poisoning.

INTRODUCTION: The death of Socrates in 399 BCE is described in Plato's dialogue, the Phaedo, written an unknown time afterwards from accounts by others. THE EVIDENCE: Socrates' death has almost always been attributed to his drinking an extract of poison hemlock, Conium maculatum, despite apparent discrepancies between the clinical features described in classical translations of the Phaedo and general clinical experience of poisoning with the toxic alkaloids it contains. EVALUATION: Recent acute philological analysis of the original Greek text has resolved many of the discrepancies by showing that the terms used in the classical translations were misinterpretations of the clinical signs described. It is also likely that the unpleasant clinical effects, such as vomiting, abdominal pain, diarrhoea and muscle fasciculation commonly described in modern reports of poison hemlock poisoning, were not mentioned to present the death of Socrates in a way consistent with his philosophical ideals and those of his pupil Plato. CONCLUSIONS: Seen in this way, the death of Socrates can be accepted as a limited case report of Conium maculatum poisoning. Even after reaching that conclusion, intriguing scientific questions remain about the toxicity of the coniine alkaloids and the mechanisms of their effects.