Toxicon最新文献

英文中文

A review of bioanalytical methods, bioaccessibility, and toxicokinetics of emerging mycotoxins enniatins and beauvericin in the context of health risk assessment

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-10 DOI: 10.1016/j.toxicon.2025.108288

Anushka Pandey , Maandvi Sharma , Manisha Bhateria , C. Yahavi , Abdul Rahman Khan , Sheelendra Pratap Singh

Mycotoxins, toxic secondary metabolites produced by fungi, often contaminate agricultural products, posing risks to human and animal health. Among these, enniatins (ENNs) and beauvericin (BEA) have gained attention due to their widespread occurrence in food and feed products and their potential toxic effects. This review comprehensively examines bioanalytical methods for detecting ENNs and BEA in biological matrices, focusing on liquid chromatography-mass spectrometry (LC-MS/MS), solid-phase extraction (SPE), and advanced sample preparation techniques. It emphasizes the significance of assessing bioaccessibility, determining the proportion of mycotoxins absorbed during digestion and their associated exposure risk. The review also explores the toxicokinetic profiles of ENNs and BEA, providing insights into their absorption, distribution, metabolism, and excretion (ADME) in humans and animals. The review also explores the biotransformation of these mycotoxins, shedding light on their metabolism into various products. Biomonitoring studies are discussed, focusing on detecting the metabolites of ENNs and BEA in biological fluids such as urine, plasma, and tissues to assess exposure. Overall, this review advocates for more research on toxicokinetics and biotransformation to fully understand the health risks of ENNs and BEA, and calls for enhanced bioanalytical detection and biomonitoring methods to improve food safety and regulatory measures.

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引用次数: 0

Pharmacology, toxicology and homeopathy of Luffa operculata (L.) Cogniaux (Cucurbitaceae): Integrative review Cogniaux (Cucurbitaceae) Luffa operculata (L.) 的药理学、毒理学和顺势疗法：综合综述。

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-08 DOI: 10.1016/j.toxicon.2025.108286

Luís Pereira-de-Morais , Paulo Ricardo Batista , Andressa de Alencar Silva , Isaac Moura Araújo , Gabriela Lucena Calixto , Thais de Souza Amorim , Marília Cavalcante Araújo , Verônica Milesi , Roseli Barbosa

Scientific evidence on the pharmacological and toxicological effects of Luffa operculata has been produced on a smaller scale, even though the species: (i) is edible; (ii) widely recognized in folk medicine for treating sinusitis and inducing abortion; (iii) and the basis of allopathic and homeopathic medicines. In this sense, the objective of this review is to characterize the pharmacological, toxicological and clinical profile of products based on L. operculata. After consulting 14 databases, as well as a free search on Google/Google Scholar and checking references, 85 studies were selected that met our eligibility criteria. After analysis and synthesis, we found that the products have a wide range of pharmacological activities in vitro, ex vivo and in vivo. The toxicological spectrum is also alarming in different segments such as: cytogenotoxicity, tissue toxicity, (sub-) acute, reproductive, neuro- and phytotoxicity. The intensity of the pharmacological and toxicological effects is variable, and seems to be conditioned by various factors (examples: plant organ, polarity of the extracting solvent, quantity, experimental model and route of administration). Clinical data show that the products have satisfactory efficacy, tolerability and safety in the treatment of upper airway diseases (especially rhinitis and sinusitis). Finally, we hope that the presentation of toxicological information in this review can guide the safe and rational use of L. operculata in folk medicine. It may also serve as scientific evidence for exploring the pharmacological potential of the species, avoiding its side effects.

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引用次数: 0

The saga of the development of laboratory tests to evaluate the neutralizing efficacy of antivenoms for the treatment of snakebite envenoming

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-06 DOI: 10.1016/j.toxicon.2025.108274

Hernán Bonilla , José María Gutiérrez

The parenteral administration of animal-derived antivenoms has been, since 1894, the mainstay of the therapy of snakebite envenoming, a neglected tropical disease that exerts a high toll of morbidity and mortality on a global basis. A key test in the development and quality control of antivenoms has been the neutralization of the lethal effect of venoms. Since the early times of antivenoms, the neutralization of venom's lethality has been predominantly based on the incubation of venom and antivenom prior to the injection in laboratory animals. The present narrative review summarizes the main milestones in the development of venom neutralization assays by antivenoms, starting with the pioneer work of Albert Calmette and Vital Brazil. Despite various initiatives along the 20th century to standardize these tests, the antivenom efficacy assays have been highly heterogeneous between laboratories and countries. Efforts carried out to understand the main variables that determine the lethality neutralization tests are discussed, together with the introduction of assays to assess the neutralization of other relevant toxic and enzymatic activities of venoms, which complement the lethality assay. In the last decades, international efforts coordinated by the World Health Organization (WHO) led to the publication of the WHO guidelines for the production and control of antivenoms, which comprise detailed descriptions of preclinical neutralization assays, including the essential test, i.e., lethality, and supplementary assays that assess other relevant toxic effects. The pain and suffering of animals in the traditional antivenom neutralization tests urge the implementation of the 3Rs principles (replacement, reduction, refinement) in antivenom efficacy assessment, and innovation is urgently needed in this field.

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引用次数: 0

A practical booklet for ultrasound-guided botulinum toxin injections

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-06 DOI: 10.1016/j.toxicon.2025.108287

Stefano Carda , Rajiv Reebye

In the last 15 years, the use of ultrasound to guide botulinum neurotoxin type A injections has been advocated by many authors, with growing evidence showing the benefits of using ultrasound guidance to improve the efficacy of injections.

Patients with spasticity may show severely altered postures, atrophy and fibrotic modifications of target muscles, leading to significant challenges in recognising and differentiating between the muscles to be injected or not. At present time, there are no available books with images that clarify how to identify and inject muscles in patients showing these problems.

Another problem we considered is the accessibility, from an economic standpoint, of medical books for clinicians in low-income countries.

We have created a practical booklet to help clinicians acquire the confidence and expertise needed to administer US-guided injections in patients with severe spasticity, combining the experience of more than 10 years in training clinicians in ultrasound-guided injections. We utilised our experience to create a method that offers a consistent way to recognise muscles, even in challenging conditions.

The aim of our booklet is to offer a reliable technique for identify and target muscles in patients with altered muscular structure and pathological postures due to spasticity, relying on easily identifiable anatomical structures such as bones, vessels or nerves, or “iconic” patterns that can easily be learned and remembered.

We have provided images and anatomical schemes, as well as ergonomic clinical pearls, to help clinicians providing reliable ultrasound-guided injections.

To reduce barriers to education, this booklet is be distributed for free without any royalties.

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引用次数: 0

DNA data (genome skims and metabarcodes) paired with chemical data demonstrate utility for retrospective analysis of forage linked to fatal poisoning of cattle

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-05 DOI: 10.1016/j.toxicon.2025.108285

Daniel Cook , Brandon Kocurek , Clint Stonecipher , Kevin D. Welch , Dale R. Gardner , Mark Mammel , Elizabeth Reed , Padmini Ramachandran , David Erickson , Seth Commichaux , Andrea Ottesen

Prepared and stored feeds, fodder, silage, and hay may be contaminated by toxic plants resulting in the loss of livestock. Several poisonous plants have played significant roles in livestock deaths from forage consumption in recent years in the Western United States including Salvia reflexa. Metagenomic data, genome skims and metabarcodes, have been used for identification and characterization of plants in complex botanical matrices including diet composition of animals, mixed forages, and herbal products. Here, chemistry, genome skims, and metabarcoding were used to retrospectively describe the composition of contaminated alfalfa hay from a case of Salvia reflexa (lanceleaf sage) poisoning that killed 165 cattle. Genome skims and metabarcoding provided similar estimates of the relative abundance of the Salvia in the hay samples when compared to chemical methods. Additionally, genome skims and metabarcoding provided similar estimates of species composition in the contaminated hay and rumen contents of poisoned animals. The data demonstrate that genome skims and DNA metabarcoding may provide useful tools for plant poisoning investigations.

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引用次数: 0

Raptors without resistance: No evidence for endogenous inhibition of rattlesnake venom metalloproteinases in a Great Plains raptor assemblage

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-04 DOI: 10.1016/j.toxicon.2025.108275

Neil R. Balchan , Tim W. Crowther , Gail Kratz , Stephen P. Mackessy

Snake venoms are complex biochemical secretions under strong selection for prey subjugation, and venoms are tightly linked to the biotic communities that snakes inhabit. Physiological adaptations for venom resistance have been identified in various snake prey species, but fewer snake predators, with research in this area largely biased towards mammalian species. Fewer investigations have assayed for the presence of resistance mechanisms in avian systems. Birds of prey (hereafter “raptors”; orders Accipitriformes, Falconiformes, and Strigiformes) represent major sources of predation for snakes. Raptor dietary habits range from snake specialists to non-snake feeders, and this continuum of snake predation frequency among species creates the ideal system in which to explore the presence and strength of venom resistance. We assayed sera from a suite of Great Plains raptors against snake venom metalloproteinases (SVMPs) of the Prairie rattlesnake (Crotalus v. viridis) to test the general hypotheses that 1) raptor sera will display elevated SVMP inhibition compared to a naïve avian model (domestic chicken; Gallus gallus) and 2) raptor species with high levels of rattlesnake predation will more effectively inhibit SVMP activity than those that are not known to feed on rattlesnakes. We found that raptors do possess elevated SVMP inhibition in comparison to a naïve avian model, but this level of inhibition remains low and is unlikely to be biologically significant in detoxifying venoms. We found no evidence suggesting that inhibitory potential of different raptor sera corresponds to the level of rattlesnake predation associated with each species. The widespread lack of SVMP inhibition in diverse raptors underscores the complexity of venom resistance dynamics in natural systems and further suggests that physiological venom resistance mechanisms may be poorly developed in birds more broadly.

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引用次数: 0

High-dose rimabotulinumtoxinB for chronic sialorrhea: A case report on the safety and efficacy of 20,000 Units injection

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-04 DOI: 10.1016/j.toxicon.2025.108276

Ali Zare Dehnavi , Farzin Pedouim , Rodolfo Savica , Khashayar Dashtipour

Chronic sialorrhea is a debilitating condition commonly seen in patients with neurological disorders such as cerebral palsy. RimabotulinumtoxinB (RIMA) is approved for treating sialorrhea, with a recommended dose range of 1500–3500 units. We report a case of a 48-year-old female with spastic quadriplegic cerebral palsy, profound intellectual disability, and chronic sialorrhea who was treated with progressively higher doses of RIMA, culminating in a dose of 20,000 units administered via injections into the parotid and submandibular glands. So far, the patient has received 22 treatment cycles of high-dosage RIMA spaced three months apart with remarkable improvement in sialorrhea without any severe adverse effects. This case demonstrates the potential safety and efficacy of using RIMA at a dose of 20,000 units for managing refractory chronic sialorrhea in patients with cerebral palsy, warranting further research into higher dosing regimens.

引用次数: 0

A novel zearalenone lactonase can effectively mitigate zearalenone-induced reproductive toxicity in gilts 一种新型玉米赤霉烯酮内酯酶能有效减轻玉米赤霉烯酮对后备母猪的生殖毒性。

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-01 DOI: 10.1016/j.toxicon.2025.108257

Jun-Chao Song , Zhe Peng , Yan-Qi Ning , Alainaa Refaie , Cheng-Fei Wang , Meng Liu , Lv-Hui Sun

Zymdetox Z-2000 is a novel zearalenone (ZEN) lactonase produced by Bacillus subtilis that can biodegrade ZEN to hydrolyzed ZEN and decarboxylated hydrolyzed ZEN with much lower estrogenic activity. This study aims to evaluate the efficacy of Zymdetox Z-2000 in mitigating the adverse effects of ZEN on the growth performance and reproductive health of gilts. A total of 80 crossbred Landrace × Yorkshire gilts (9.82 ± 0.79 kg) were allocated into five groups and received a basal diet (BD; CON), BD supplemented with 0.4 mg/kg ZEN (ZEN), BD plus ZEN with 0.01% Zymdetox Z-2000 (ZEN-Zym), BD plus ZEN with 0.01% coated Zymdetox Z-2000 (ZEN-CoZym), and BD plus ZEN with 0.1% B. subtilis (ZEN-Bs), respectively, for 28 days. Compared to the CON group, ZEN treatment reduced the body weight gain of the gilts, increased vulva area and vaginal and uterus indices, and increased serum aspartate aminotransferase (AST) activity and estradiol (E2) concentration. ZEN treatment also induced ovaries histopathology changes, decreased the total antioxidant capacity (T-AOC) in uterus but increased T-AOC in ovaries, and increased ZEN concentration in stomach and duodenum than those of the CON group. Interestingly, dietary supplementation with the three products effectively alleviated these ZEN-induced adverse effects, as Zymdetox Z-2000 and coated Zymdetox Z-2000 showed better mitigating effects than B. subtilis. In conclusion, ZEN exposure impaired the growth and reproductive health of gilts, while dietary supplementation with Zymdetox Z-2000 and coated Zymdetox Z-2000 can effectively alleviate ZEN-induced reproductive toxicity in gilts.

Zymdetox Z-2000是一种由枯草芽孢杆菌产生的新型玉米赤霉烯酮（ZEN）内酯酶，可将ZEN生物降解为水解ZEN和脱羧水解ZEN，具有较低的雌激素活性。本研究旨在评价Zymdetox Z-2000在缓解ZEN对后备母猪生长性能和生殖健康不利影响方面的效果。选取80头长×大杂交后备母猪（体重9.82±0.79 kg），随机分为5组，分别饲喂基础饲粮(BD；BD + ZEN添加0.01% Zymdetox Z-2000 (ZEN- zym)， BD + ZEN添加0.01%包被Zymdetox Z-2000 (ZEN- cozym)， BD + ZEN添加0.1%枯草芽胞杆菌（ZEN- bs），分别处理28 d。与CON组相比，ZEN处理降低了母猪增重，增加了外阴面积、阴道和子宫指数，提高了血清天冬氨酸转氨酶（AST）活性和雌二醇（E2）浓度。与CON组相比，ZEN组卵巢组织病理学改变，子宫总抗氧化能力（T-AOC）降低，卵巢总抗氧化能力（T-AOC）升高，胃和十二指肠ZEN浓度升高。有趣的是，在饮食中添加这三种产品可以有效缓解zen引起的不良反应，其中Zymdetox Z-2000和被包衣的Zymdetox Z-2000的缓解效果优于枯草芽孢杆菌。综上所述，ZEN暴露会损害后备母猪的生长和生殖健康，而饲粮中添加Zymdetox Z-2000和包被Zymdetox Z-2000能有效减轻ZEN对后备母猪的生殖毒性。

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引用次数: 0

Medicinal plants and home remedies for scorpion sting envenomation: Why proven therapies should take precedence pending robust evidence

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-01 DOI: 10.1016/j.toxicon.2025.108261

Eduardo Alfonso Hernández-Muñoz , Adolfo Borges , Eugenio Vladimir Zavala-Sánchez

引用次数: 0

BoNT/Action beyond neurons

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-01 DOI: 10.1016/j.toxicon.2025.108250

Sara Marinelli

Botulinum neurotoxin type A (BoNT/A) has expanded its therapeutic uses beyond neuromuscular disorders to include treatments for various pain syndromes and neurological conditions. Originally recognized for blocking acetylcholine release at neuromuscular junctions, BoNT/A's effects extend to both peripheral and central nervous systems. Its ability to undergo retrograde transport allows BoNT/A to modulate synaptic transmission and reduce pain centrally, influencing neurotransmitter systems beyond muscle control.

BoNT/A also interacts with glial cells, such as Schwann cells, satellite glial cells, astrocytes, microglia, and oligodendrocytes. Schwann cells, key to peripheral nerve regeneration, are directly influenced by BoNT/A, which promotes their proliferation and enhances remyelination. Satellite glial cells, involved in sensory neuron regulation, show reduced glutamate release in response to BoNT/A, aiding in pain relief.

In the CNS, BoNT/A modulates astrocyte activity, reducing excitotoxicity and inflammation, which is relevant in conditions like epilepsy. Microglia, the CNS's immune cells, shift from a pro-inflammatory to a neuroprotective state when treated with BoNT/A, enhancing tissue repair. Additionally, BoNT/A promotes oligodendrocyte survival and remyelination, especially after spinal cord injury.

Overall, BoNT/A's ability to target both neurons and glial cells presents a multifaceted therapeutic strategy for neurological disorders, pain management, and CNS repair. Further research is necessary to fully elucidate its mechanisms and optimize its clinical application.

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