Toxins

20 pages, 3411 KiB

Open AccessArticle

Veratridine Induces Vasorelaxation in Mouse Cecocolic Mesenteric Arteries

by Joohee Park, Christina Sahyoun, Jacinthe Frangieh, Léa Réthoré, Coralyne Proux, Linda Grimaud, Emilie Vessières, Jennifer Bourreau, César Mattei, Daniel Henrion, Céline Marionneau, Ziad Fajloun, Claire Legendre and Christian Legros

Toxins 2024, 16(12), 533; https://doi.org/10.3390/toxins16120533 - 10 Dec 2024

Abstract

The vegetal alkaloid toxin veratridine (VTD) is a selective voltage-gated Na⁺ (Na_V) channel activator, widely used as a pharmacological tool in vascular physiology. We have previously shown that Na_V channels, expressed in arteries, contribute to vascular tone in mouse [...] Read more.

The vegetal alkaloid toxin veratridine (VTD) is a selective voltage-gated Na⁺ (Na_V) channel activator, widely used as a pharmacological tool in vascular physiology. We have previously shown that Na_V channels, expressed in arteries, contribute to vascular tone in mouse mesenteric arteries (MAs). Here, we aimed to better characterize the mechanisms of action of VTD using mouse cecocolic arteries (CAs), a model of resistance artery. Using wire myography, we found that VTD induced vasorelaxation in mouse CAs. This VTD-induced relaxation was insensitive to prazosin, an α1-adrenergic receptor antagonist, but abolished by atropine, a muscarinic receptor antagonist. Indeed, VTD–vasorelaxant effect was totally inhibited by the Na_V channel blocker tetrodotoxin (0.3 µM), the NO synthase inhibitor L-NNA (20 µM), and low extracellular Na⁺ concentration (14.9 mM) and was partially blocked by the NCX1 antagonist SEA0400 (45.4% at 1 µM). Thus, we assumed that the VTD-induced vasorelaxation in CAs was due to acetylcholine release by parasympathetic neurons, which induced NO synthase activation mediated by the NCX1-Ca²⁺ entry mode in endothelial cells (ECs). We demonstrated NCX1 expression in ECs by RT-qPCR and immunohisto- and western immunolabelling. VTD did not induce an increase in intracellular Ca²⁺ ([Ca²⁺]i), while SEA0400 partially blocked acetylcholine-triggered [Ca²⁺]i elevations in Mile Sven 1 ECs. Altogether, these results illustrate that VTD activates Na_V channels in parasympathetic neurons and then vasorelaxation in resistance arteries, which could explain arterial hypotension after VTD intoxication. Full article

(This article belongs to the Special Issue Toxins: From the Wild to the Lab)

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14 pages, 3562 KiB

Open AccessArticle

Venom from Loxosceles Spiders Collected in Southeastern and Northeastern Brazilian Regions Cause Hemotoxic Effects on Human Blood Components

by Rafaela Silva-Magalhães, Ayla Mel Gomes dos Santos, Ana Luiza Silva-Araújo, Pamella Luize Peres-Damásio, Valéria Gonçalves de Alvarenga, Luciana Souza de Oliveira, Eladio Flores Sanchez, Carlos Chávez-Olórtegui, Luana Silveira da Rocha Nowicki Varela, Ana Luiza Bittencourt Paiva and Clara Guerra-Duarte

Toxins 2024, 16(12), 532; https://doi.org/10.3390/toxins16120532 - 10 Dec 2024

Abstract

Spiders of the genus Loxosceles represent a public health problem in Brazil due to the severity of the cutaneous and systemic effects that may result from their bite. In the systemic form of loxoscelism, hemolytic anemia, thrombocytopenia, and disseminated intravascular coagulation can occur. [...] Read more.

Spiders of the genus Loxosceles represent a public health problem in Brazil due to the severity of the cutaneous and systemic effects that may result from their bite. In the systemic form of loxoscelism, hemolytic anemia, thrombocytopenia, and disseminated intravascular coagulation can occur. Despite the seriousness of Loxosceles accidents, the venom of some species has not yet been properly characterized considering these hemotoxic effects, such as that of Loxosceles amazonica, Loxosceles aff. Variegata, and Loxosceles similis. To better understand their toxic potential, this study aimed to characterize the hematotoxic properties of these Loxosceles venoms. The crude venom was obtained from specimens of L. amazonica, L. aff. Variegata, and L. similis available from Funed’s arachnidary. In washed platelets, L. aff. variegata inhibited platelet aggregation induced by collagen and convulxin, whereas L. amazonica and L. similis venoms were able to induce platelet aggregation. In the in vitro hemolysis assays, all venoms experimentally induced direct hemolysis of human erythrocytes in a concentration-dependent manner, with different intensities. Furthermore, evidence suggest that the ABO and Rh systems may influence hemolytic activity. Finally, the studied Loxosceles venoms degraded fibrinogen, suggesting possible alterations in the coagulation cascade. Based in the here-presented preliminary study, in vivo assays in model animals are needed to verify the real toxic potential of these species’ venom, building up knowledge to elucidate the action of Loxosceles venoms in blood. Full article

(This article belongs to the Special Issue Brown Spider Venom Toxins: Biological Activities, Molecular Mechanisms, Cell Biology, Biotechnological Applications, and Targets for the Therapeutic Management of Loxoscelism)

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26 pages, 8285 KiB

Open AccessArticle

Image Analysis and Untargeted Metabolomics Reveal Potential Phytotoxins from Fusarium venenatum Against Major Parasitic Weed Phelipanche ramosa (L.) Pomel

by Ana Bendejacq-Seychelles, Lisa Martinez, Anaïs Corréard, Jean Chrisologue Totozafy, Christian Steinberg, Jean-Bernard Pouvreau, Carole Reibel, Grégory Mouille, Samuel Mondy, Lucie Poulin and Stéphanie Gibot-Leclerc

Toxins 2024, 16(12), 531; https://doi.org/10.3390/toxins16120531 - 10 Dec 2024

Abstract

Branched broomrape (Phelipanche ramosa (L.) Pomel), an obligate parasitic weed with a wide host range, is known for its devasting effects on many crops worldwide. Soil fungi, notably Fusarium sp., are described as pathogenic to broomrape, while the hypothesis of the phytotoxicity [...] Read more.

Branched broomrape (Phelipanche ramosa (L.) Pomel), an obligate parasitic weed with a wide host range, is known for its devasting effects on many crops worldwide. Soil fungi, notably Fusarium sp., are described as pathogenic to broomrape, while the hypothesis of the phytotoxicity of fusaric acid produced by F. verticillioides for parasitic weeds of the genus Orobanche has been proposed. Using image analysis and untargeted metabolomics, this study investigated fungal metabolites phytotoxic for P. ramosa and produced by the F. venenatum MIAE02836 strain, isolated from symptomatic broomrapes and identified as a promising candidate for broomrape biocontrol. Phytotoxicity tests of crude extracts from the fungus alone or in interaction with broomrape on P. ramosa microcalli and quantification of necrosis by image analysis confirmed the phytotoxic potential of F. venenatum MIAE02836 metabolites towards the early developmental stages of P. ramosa. Data analysis of a non-targeted metabolomics approach revealed numerous metabolites produced by F. venenatum MIAE02836. Four of them, accumulated during interaction with the parasitic plant, are known for their phytotoxic potential: maculosin, cyclo(Leu-Phe), phenylalanyl-D-histidine and anguidine. These results suggest that combining image acquisition of the microcalli screening test and untargeted metabolomic approach is an interesting and relevant method to characterize phytotoxic fungal metabolites. Full article

(This article belongs to the Section Mycotoxins)

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6 pages, 189 KiB

Open AccessEditorial

Botulinum Toxin and Migraine: Goals and Perspectives

by Maria Pia Prudenzano

Toxins 2024, 16(12), 530; https://doi.org/10.3390/toxins16120530 - 10 Dec 2024

Abstract

This Special Issue aims to provide an updated overview of the current state and future perspectives of botulinum toxin treatment for migraine [...] Full article

(This article belongs to the Special Issue Botulinum Toxin and Migraine: Goals and Perspectives)

14 pages, 1043 KiB

Open AccessArticle

Integrating Telemedicine in Botulinum Toxin Type-A Treatment for Spasticity Management: Perspectives and Challenges from Italian Healthcare Professionals

by Stefania Spina, Salvatore Facciorusso, Nicoletta Cinone, Luigi Santoro, Anna Castagna, Marina Ramella, Franco Molteni, Andrea Santamato and The Collaborative Working Group

Toxins 2024, 16(12), 529; https://doi.org/10.3390/toxins16120529 - 7 Dec 2024

Abstract

(1) Background: Telemedicine is a vital tool for enhancing healthcare accessibility and outcomes at reduced costs. This study aimed to assess the usability of the Maia Connected Care telemedicine platform for managing spasticity in patients receiving botulinum toxin type-A, focusing on the perspectives [...] Read more.

(1) Background: Telemedicine is a vital tool for enhancing healthcare accessibility and outcomes at reduced costs. This study aimed to assess the usability of the Maia Connected Care telemedicine platform for managing spasticity in patients receiving botulinum toxin type-A, focusing on the perspectives of Italian physiatrists with expertise in this treatment. (2) Methods: Conducted from March 2023 to June 2023, this multicenter survey involved 15 Italian physicians who used the platform for teleconsultations. Data collected included demographic details, responses to the Telemedicine Usability Questionnaire, and physician insights on patient satisfaction, treatment effectiveness, and implementation challenges in telehealth. (3) Results: The platform demonstrated high usability, with strong physician satisfaction due to its user-friendly interface and quality of interactions. A majority expressed willingness to continue telehealth for spasticity management, noting its effectiveness in improving patient satisfaction and outcomes. Challenges included replicating the depth of in-person consultations and addressing issues like reimbursement and telehealth standardization. (4) Conclusions: This study highlights telemedicine’s potential for spasticity management and clinician satisfaction, while underscoring the need for improvements in simulating in-person experiences and addressing systemic issues. The absence of patient perspectives represents a limitation, advocating for future research to optimize telemedicine practices and evaluate long-term clinical impacts. Full article

(This article belongs to the Section Bacterial Toxins)

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39 pages, 6873 KiB

Open AccessReview

Exploring Mycolactone—The Unique Causative Toxin of Buruli Ulcer: Biosynthetic, Synthetic Pathways, Biomarker for Diagnosis, and Therapeutic Potential

by Gideon Atinga Akolgo, Kingsley Bampoe Asiedu and Richard Kwamla Amewu

Toxins 2024, 16(12), 528; https://doi.org/10.3390/toxins16120528 - 6 Dec 2024

Abstract

Mycolactone is a complex macrolide toxin produced by Mycobacterium ulcerans, the causative agent of Buruli ulcer. The aim of this paper is to review the chemistry, biosynthetic, and synthetic pathways of mycolactone A/B to help develop an understanding of the mode of [...] Read more.

Mycolactone is a complex macrolide toxin produced by Mycobacterium ulcerans, the causative agent of Buruli ulcer. The aim of this paper is to review the chemistry, biosynthetic, and synthetic pathways of mycolactone A/B to help develop an understanding of the mode of action of these polyketides as well as their therapeutic potential. The synthetic work has largely been driven by the desire to afford researchers enough (≥100 mg) of the pure toxins for systematic biological studies toward understanding their very high biological activities. The review focuses on pioneering studies of Kishi which elaborate first-, second-, and third-generation approaches to the synthesis of mycolactones A/B. The three generations focused on the construction of the key intermediates required for the mycolactone synthesis. Synthesis of the first generation involves assignment of the relative and absolute stereochemistry of the mycolactones A and B. This was accomplished by employing a linear series of 17 chemical steps (1.3% overall yield) using the mycolactone core. The second generation significantly improved the first generation in three ways: (1) by optimizing the selection of protecting groups; (2) by removing needless protecting group adjustments; and (3) by enhancing the stereoselectivity and overall synthetic efficiency. Though the synthetic route to the mycolactone core was longer than the first generation, the overall yield was significantly higher (8.8%). The third-generation total synthesis was specifically aimed at an efficient, scalable, stereoselective, and shorter synthesis of mycolactone. The synthesis of the mycolactone core was achieved in 14 linear chemical steps with 19% overall yield. Furthermore, a modular synthetic approach where diverse analogues of mycolactone A/B were synthesized via a cascade of catalytic and/or asymmetric reactions as well as several Pd-catalyzed key steps coupled with hydroboration reactions were reviewed. In addition, the review discusses how mycolactone is employed in the diagnosis of Buruli ulcer with emphasis on detection methods of mass spectrometry, immunological assays, RNA aptamer techniques, and fluorescent-thin layer chromatography (f-TLC) methods as diagnostic tools. We examined studies of the structure–activity relationship (SAR) of various analogues of mycolactone. The paper highlights the multiple biological consequences associated with mycolactone such as skin ulceration, host immunomodulation, and analgesia. These effects are attributed to various proposed mechanisms of actions including Wiskott–Aldrich Syndrome protein (WASP)/neural Wiskott–Aldrich Syndrome protein (N-WASP) inhibition, Sec61 translocon inhibition, angiotensin II type 2 receptor (AT2R) inhibition, and inhibition of mTOR. The possible application of novel mycolactone analogues produced based on SAR investigations as therapeutic agents for the treatment of inflammatory disorders and inflammatory pain are discussed. Additionally, their therapeutic potential as anti-viral and anti-cancer agents have also been addressed. Full article

(This article belongs to the Section Mycotoxins)

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20 pages, 2006 KiB

Open AccessArticle

Biological and Chemical Management of Aspergillus carbonarius and Ochratoxin A in Vineyards

by Maria K. Iliadi, Maria Varveri and Dimitrios I. Tsitsigiannis

Toxins 2024, 16(12), 527; https://doi.org/10.3390/toxins16120527 - 6 Dec 2024

Abstract

Ochratoxin A (OTA) is a widely distributed mycotoxin and potent carcinogen produced by several fungal genera, but mainly by Aspergillus carbonarius. Grape contamination occurs in vineyards during the period between veraison and pre-harvest, and it is the main cause of OTA’s presence [...] Read more.

Ochratoxin A (OTA) is a widely distributed mycotoxin and potent carcinogen produced by several fungal genera, but mainly by Aspergillus carbonarius. Grape contamination occurs in vineyards during the period between veraison and pre-harvest, and it is the main cause of OTA’s presence in wine. The aim of the current study was the evaluation of 6 chemical and 11 biological plant protection products (PPPs) and biocontrol agents in commercial vineyards of the two important Greek white wine varieties cv. Malagousia and cv. Savatiano. The PPPs were applied in a 4-year vineyard study as single treatments or/and in combinations as part of IPM systems. Subsequently, nine strains of Aspergillus carbonarius were investigated for their sensitivity against seven active compounds of synthetic fungicides. During the multi-year field trials, various novel management systems, including consortia of biocontrol agents, were revealed to be effective against Aspergillus sour rot and OTA production. However, expected variability was observed in the experimental results, indicating the dynamic character of biological systems and highlighting the possible inconsistency of PPPs’ efficacy in a changing environment. Furthermore, the IPM systems developed effectuated an optimized control of A. carbonarius, leading to 100% inhibition of OTA contamination, showing the importance of using both chemical and biological PPPs for disease management and prevention of fungal fungicide resistance. Finally, the majority of A. carbonarius tested strains were found to be sensitive against the pure active compounds used (fludioxonil, azoxystrobin, chlorothalonil, tebuconazole, cyprodinil, pyrimethanil and boscalid), with only a few exceptions of developed resistance towards boscalid. Full article

(This article belongs to the Special Issue Toxins: 15th Anniversary)

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19 pages, 6558 KiB

Open AccessArticle

Real-Time Observation of Clickable Cyanotoxin Synthesis in Bloom-Forming Cyanobacteria Microcystis aeruginosa and Planktothrix agardhii

by Rainer Kurmayer and Rubén Morón Asensio

Toxins 2024, 16(12), 526; https://doi.org/10.3390/toxins16120526 - 5 Dec 2024

Abstract

Recently, the use of click chemistry for localization of chemically modified cyanopeptides has been introduced, i.e., taking advantage of promiscuous adenylation (A) domains in non-ribosomal peptide synthesis (NRPS), allowing for the incorporation of clickable non-natural amino acids (non-AAs) into their peptide products. In [...] Read more.

Recently, the use of click chemistry for localization of chemically modified cyanopeptides has been introduced, i.e., taking advantage of promiscuous adenylation (A) domains in non-ribosomal peptide synthesis (NRPS), allowing for the incorporation of clickable non-natural amino acids (non-AAs) into their peptide products. In this study, time-lapse experiments have been performed using pulsed feeding of three different non-AAs in order to observe the synthesis or decline of azide- or alkyne-modified microcystins (MCs) or anabaenopeptins (APs). The cyanobacteria Microcystis aeruginosa and Planktothrix agardhii were grown under maximum growth rate conditions (r = 0.35–0.6 and 0.2–0.4 (day⁻¹), respectively) in the presence of non-AAs for 12–168 h. The decline of the azide- or alkyne-modified MC or AP was observed via pulse-feeding. In general, the increase in clickable MC/AP in peptide content reached a plateau after 24–48 h and was related to growth rate, i.e., faster-growing cells also produced more clickable MC/AP. Overall, the proportion of clickable MC/AP in the intracellular fraction correlated with the proportion observed in the dissolved fraction. Conversely, the overall linear decrease in clickable MC/AP points to a rather constant decline via dilution by growth instead of a regulated or induced release in the course of the synthesis process. Full article

(This article belongs to the Special Issue Harmful Algae in a Changing World: Where Did We Come from and Where Are We Going?)

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13 pages, 2371 KiB

Open AccessArticle

Epsilon Toxin from Clostridium perfringens Induces the Generation of Extracellular Vesicles in HeLa Cells Overexpressing Myelin and Lymphocyte Protein

by Jonatan Dorca-Arévalo, Antonio Santana-Ruiz, Benjamín Torrejón-Escribano, Mireia Martín-Satué and Juan Blasi

Toxins 2024, 16(12), 525; https://doi.org/10.3390/toxins16120525 - 4 Dec 2024

Abstract

Epsilon toxin (ETX) from Clostridium perfringens is a pore-forming toxin (PFT) that crosses the blood–brain barrier and binds to myelin structures. In in vitro assays, ETX causes oligodendrocyte impairment, subsequently leading to demyelination. In fact, ETX has been associated with triggering multiple sclerosis. [...] Read more.

Epsilon toxin (ETX) from Clostridium perfringens is a pore-forming toxin (PFT) that crosses the blood–brain barrier and binds to myelin structures. In in vitro assays, ETX causes oligodendrocyte impairment, subsequently leading to demyelination. In fact, ETX has been associated with triggering multiple sclerosis. Myelin and lymphocyte protein (MAL) is widely considered to be the receptor for ETX as its presence is crucial for the effects of ETX on the plasma membrane of host cells that involve pore formation, resulting in cell death. To overcome the pores formed by PFTs, some host cells produce extracellular vesicles (EVs) to reduce the amount of pores inserted into the plasma membrane. The formation of EVs has not been studied for ETX in host cells. Here, we generated a highly sensitive clone from HeLa cells overexpressing the MAL-GFP protein in the plasma membrane. We observed that ETX induces the formation of EVs. Moreover, the MAL protein and ETX oligomers are found in these EVs, which are a very useful tool to decipher and study the mode of action of ETX and characterize the mechanisms involved in the binding of ETX to its receptor. Full article

(This article belongs to the Special Issue Toxin-Host Interaction of Clostridium Toxins)

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13 pages, 6199 KiB

Open AccessArticle

Bicistronic Vector Expression of Recombinant Jararhagin-C and Its Effects on Endothelial Cells

by Karla Fernanda Ferraz, Lhiri Hanna De Lucca Caetano, Daniele Pereira Orefice, Paula Andreia Lucas Calabria, Maisa Splendore Della-Casa, Luciana Aparecida Freitas-de-Sousa, Emidio Beraldo-Neto, Sabri Saeed Sanabani, Geraldo Santana Magalhães and Patricia Bianca Clissa

Toxins 2024, 16(12), 524; https://doi.org/10.3390/toxins16120524 - 3 Dec 2024

Abstract

Jararhagin-C (JarC) is a protein from the venom of Bothrops jararaca consisting of disintegrin-like and cysteine-rich domains. JarC shows a modulating effect on angiogenesis and remodeling of extracellular matrix constituents, improving wound healing in a mouse experimental model. JarC is purified from crude [...] Read more.

Jararhagin-C (JarC) is a protein from the venom of Bothrops jararaca consisting of disintegrin-like and cysteine-rich domains. JarC shows a modulating effect on angiogenesis and remodeling of extracellular matrix constituents, improving wound healing in a mouse experimental model. JarC is purified from crude venom, and the yield is less than 1%. The aim of this work was to obtain the recombinant form of JarC and to test its biological activity. For this purpose, the bicistronic vector pSUMOUlp1 was used. This vector allowed the expression of the recombinant toxin JarC (rJarC) in fusion with the small ubiquitin-related modifier (SUMO) as well as the SUMO protease Ulp1. After expression, this protease was able to efficiently remove SUMO from rJarC inside the bacteria. rJarC free from SUMO was purified at the expected molecular mass and recognized by polyclonal anti-jararhagin antibodies. In terms of biological activity, both the native and recombinant forms showed no toxicity to the HUVEC cell line CRL1730 and were effective in modulating cell migration activity in the experimental in vitro model. These results demonstrate the successful production of rJarC and the preservation of its biological activity, which may facilitate further investigations into the therapeutic potential of this snake venom-derived protein. Full article

(This article belongs to the Special Issue Animals Venom in Drug Discovery: A Valuable Therapeutic Tool)

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11 pages, 506 KiB

Open AccessArticle

The Association Between Serum Trimethylamine N-Oxide and Arterial Stiffness in Chronic Peritoneal Dialysis Patients: A Cross-Sectional Study

by Po-Yu Huang, Yu-Li Lin, Yi-Hsin Chen, Szu-Chun Hung, Hung-Hsiang Liou, Jen-Pi Tsai and Bang-Gee Hsu

Toxins 2024, 16(12), 523; https://doi.org/10.3390/toxins16120523 - 3 Dec 2024

Abstract

Trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, participates in the atherogenesis and vascular stiffening that is closely linked with cardiovascular (CV) complications and related deaths in individuals with kidney failure undergoing peritoneal dialysis (PD) therapy. In these patients, arterial stiffness (AS) is [...] Read more.

Trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, participates in the atherogenesis and vascular stiffening that is closely linked with cardiovascular (CV) complications and related deaths in individuals with kidney failure undergoing peritoneal dialysis (PD) therapy. In these patients, arterial stiffness (AS) is also an indicator of adverse CV outcomes. This study assessed the correlation between serum TMAO concentration quantified with high-performance liquid chromatography and mass spectrometry and central AS measured by carotid–femoral pulse wave velocity (cfPWV) in patients with chronic PD. Of the 160 participants included, 23.8% had a cfPWV of ≥10 m/s, which fulfilled the AS criteria. Multivariable logistic regression analysis revealed that TMAO, age, and waist circumference were positively associated with AS. Multivariable stepwise linear regression showed that underlying diabetes, advanced age, waist circumference, systolic blood pressure, and logarithmic-transformed TMAO were independently correlated with cfPWV. The area under the receiver operating characteristic curve for TMAO in differentiating AS from non-AS was 0.737. In conclusion, serum TMAO level was significantly independently correlated with central AS among participants undergoing PD for end-stage kidney failure. Full article

(This article belongs to the Section Uremic Toxins)

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16 pages, 6122 KiB

Open AccessArticle

First Report of Accumulation of Lyngbyatoxin-A in Edible Shellfish in Aotearoa New Zealand from Marine Benthic Cyanobacteria

by Laura Biessy, Jonathan Puddick, Susanna A. Wood, Andrew I. Selwood, Megan Carbines and Kirsty F. Smith

Toxins 2024, 16(12), 522; https://doi.org/10.3390/toxins16120522 - 3 Dec 2024

Abstract

This study reports the first documented accumulation of lyngbyatoxin-a (LTA), a cyanotoxin produced by marine benthic cyanobacteria, in edible shellfish in Aotearoa New Zealand. The study investigates two bloom events in 2022 and 2023 on Waiheke Island, where hundreds of tonnes of marine [...] Read more.

This study reports the first documented accumulation of lyngbyatoxin-a (LTA), a cyanotoxin produced by marine benthic cyanobacteria, in edible shellfish in Aotearoa New Zealand. The study investigates two bloom events in 2022 and 2023 on Waiheke Island, where hundreds of tonnes of marine benthic cyanobacterial mats (mBCMs) washed ashore each summer. Genetic analysis identified the cyanobacterium responsible for the blooms as Okeania sp., a genus typically found in tropical marine ecosystems. Analysis by liquid chromatography–tandem mass spectrometry indicated that the cyanobacteria produced a potent dermatoxin, lyngbyatoxin-a (LTA), and that LTA had accumulated in marine snails, rock oysters and cockles collected near the mats. Snails contained the highest levels of LTA (up to 10,500 µg kg⁻¹). The study also demonstrated that the LTA concentration was stable in composted mats for several months. The presence of LTA in edible species and its stability over time raise concerns about the potential health risks to humans consuming LTA-contaminated seafood. This underlines the need for further studies assessing the risks of human exposure to LTA through seafood consumption, particularly as climate change and eutrophication are expected to increase the frequency of mBCM blooms. The study highlights the need to develop public health risk management strategies for mBCMs. Full article

(This article belongs to the Special Issue Marine Biotoxins: Bioactivities, Identification, and Potential Bioprocesses)

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8 pages, 1439 KiB

Open AccessArticle

Antivenom Administration After Rattlesnake Envenoming in Arizona Does Not Directly Diminish Pain

by Vance G. Nielsen, Darien L. Stratton, Tyler M. Hoelscher, Hannah L. Nakamura, Matthew M. Cornelison, William F. Rushton and Geoffrey T. Smelski

Toxins 2024, 16(12), 521; https://doi.org/10.3390/toxins16120521 - 2 Dec 2024

Abstract

The onset, progression, and severity of pain following rattlesnake envenomation are highly variable between patients. Pain can be severe and persistent, seemingly refractory to opioid analgesics. The ability of antivenom to directly relieve pain has not been well studied. We reviewed poison center [...] Read more.

The onset, progression, and severity of pain following rattlesnake envenomation are highly variable between patients. Pain can be severe and persistent, seemingly refractory to opioid analgesics. The ability of antivenom to directly relieve pain has not been well studied. We reviewed poison center charts of rattlesnake envenomations between 1 January 2018, and 31 December 2022. Demographic data as well as details of antivenom usage and pain severity were collected. Patients were coded in one of three categories: without pain (Pain 0), well controlled pain (Pain 1), and opioid refractory pain (Pain 2). A total of 289 patients met the inclusion criteria, with 140 receiving Anavip antivenom and 149 receiving Crofab. Patient characteristics were different between both cohorts. There were no significant differences in the number of Anavip vials used between the Pain 1 and Pain 2 groups. However, patients in the Crofab Pain 2 group received more antivenom compared to Pain 1. Importantly, Pain 3 patients were treated with the highest amount of antivenom in both the Crofab and Anavip cohorts. Despite the higher doses of antivenom used, these patients also experienced the greatest pain. These data suggest that antivenom alone may have minimal analgesic benefits. Full article

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14 pages, 920 KiB

Open AccessArticle

Age Is Just a Number: Ontogenetic Conservation in Activation of Blood Clotting Factors VII, X, and XII by Caucasus Blunt-Nosed Viper (Macrovipera lebetina obtusa) Venoms

by Katrina Kempson, Abhinandan Chowdhury, Aude Violette, Rudy Fourmy, Raul Soria and Bryan G. Fry

Toxins 2024, 16(12), 520; https://doi.org/10.3390/toxins16120520 - 2 Dec 2024

Abstract

This study examined the pathophysiological effects of venoms from neonate and adult specimens of the viperid snake Macrovipera lebetina obtusa, focusing on their ability to activate various blood clotting factors in human plasma. All venoms exhibited strong procoagulant properties. In concentration–response tests, [...] Read more.

This study examined the pathophysiological effects of venoms from neonate and adult specimens of the viperid snake Macrovipera lebetina obtusa, focusing on their ability to activate various blood clotting factors in human plasma. All venoms exhibited strong procoagulant properties. In concentration–response tests, the clotting potency of the neonate venoms fell within the range of their parents’ maximum clotting velocities and areas under the curve. Intriguingly, females were more potent than males within each age group, but this requires a larger sample size to confirm. Antivenom neutralization efficacy was equipotent across age groups. The venoms potently activated Factor X (FX) robustly, consistent with previous knowledge of this genus. For the first time, the ability to activate Factors VII (FVII) and XII (FXII) was identified in this genus, with FXII exhibiting particularly strong activation. The study found no significant ontogenetic variation in procoagulant venom potency on human plasma, convergent with the Daboia genus, the other large-bodied lineage within the Palearctic viperid clade. However, the activation of FXII and FVII reveals previously undocumented pathways in the procoagulant activity of these venoms, contributing to the broader understanding of venom evolution and its clinical impacts. These findings have implications for venom biodiscovery and the development of antivenoms, highlighting the complexity of clotting factor activation beyond traditional investigations that have myopically focused upon FX and prothrombin pathways, thereby underscoring the importance of exploring additional clotting factors. Full article

(This article belongs to the Section Animal Venoms)

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30 pages, 2355 KiB

Open AccessReview

The Role of Snake Venom Proteins in Inducing Inflammation Post-Envenomation: An Overview on Mechanistic Insights and Treatment Strategies

by Sudharshan Rao, Nisha Reghu, Bipin Gopalakrishnan Nair and Muralidharan Vanuopadath

Toxins 2024, 16(12), 519; https://doi.org/10.3390/toxins16120519 - 2 Dec 2024

Abstract

The intricate combination of organic and inorganic compounds found in snake venom includes proteins, peptides, lipids, carbohydrates, nucleotides, and metal ions. These components work together to immobilise and consume prey through processes such as paralysis and hypotension. Proteins, both enzymatic and non-enzymatic, form [...] Read more.

The intricate combination of organic and inorganic compounds found in snake venom includes proteins, peptides, lipids, carbohydrates, nucleotides, and metal ions. These components work together to immobilise and consume prey through processes such as paralysis and hypotension. Proteins, both enzymatic and non-enzymatic, form the primary components of the venom. Based on the effects they produce, venom can be classified as neurotoxic, hemotoxic, and cytotoxic. Studies have shown that, after envenomation, proteins in snake venom also contribute significantly to the induction of inflammatory responses which can either have systemic or localized consequences. This review delves into the mechanisms by which snake venom proteins trigger inflammatory responses, focusing on key families such as phospholipase A₂, metalloproteinases, serine proteases, C-type lectins, cysteine-rich secretory proteins, and L-amino acid oxidase. In addition, the role of venom proteins in activating various inflammatory pathways, including the complement system, inflammasomes, and sterile inflammation are also summarized. The available therapeutic options are examined, with a focus on antivenom therapy and its side effects. In general, this review offers a comprehensive understanding of the inflammatory mechanisms that are triggered by snake venom proteins and the side effects of antivenom treatment. All these emphasize the need for effective strategies to mitigate these detrimental effects. Full article

(This article belongs to the Special Issue Snake Venom: Toxicology and Associated Countermeasures)

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14 pages, 2777 KiB

Open AccessArticle

Effects of Culture Systems and Nutrients on the Growth and Toxin Production of Karenia selliformis

by Xizhen Wu, Guixiang Wang, Jiangbing Qiu, Aifeng Li and Philipp Hess

Toxins 2024, 16(12), 518; https://doi.org/10.3390/toxins16120518 - 1 Dec 2024

Abstract

Harmful algal blooms (HABs) formed by toxic microalgae have seriously threatened marine ecosystems and food safety and security in recent years. Among them, Karenia selliformis has attracted the attention of scientists and society due to its acute and rapid neurotoxicity in mice. Herein, [...] Read more.

Harmful algal blooms (HABs) formed by toxic microalgae have seriously threatened marine ecosystems and food safety and security in recent years. Among them, Karenia selliformis has attracted the attention of scientists and society due to its acute and rapid neurotoxicity in mice. Herein, the growth and gymnodimine A (GYM-A) production of K. selliformis were investigated in diverse culture systems with different surface-to-volume (S/V) ratios and nitrogen/phosphorus concentrations. The results showed that the specific growth rates (μ), maximal cell yields, and GYM-A production levels of K. selliformis increased with higher S/V, but no significant differences were observed under different culture volumes with the same S/V, which indicated that light penetration and gas exchange in the seawater culture systems actually influenced the growth and GYM-A production of K. selliformis. The maximum cell density and photosynthetic efficiency of K. selliformis decreased under nitrogen (N) and phosphorus (P) deficiency, suggesting that the growth of K. selliformis was significantly inhibited by the deficiency in N or P. Both N and P limitation conditions, especially P deficiency, promoted the cellular GYM-A quotas of K. selliformis. In this study, a scientific basis is provided for understanding the effects of culture systems and nutrient concentrations on the growth and toxin production of K. selliformis. Full article

(This article belongs to the Section Marine and Freshwater Toxins)

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17 pages, 2155 KiB

Open AccessArticle

A Multi-Enzyme Complex That Mitigates Hepatotoxicity, Improves Egg Production and Quality, and Enhances Gut and Liver Health in Laying Hens Exposed to Trace Aflatoxin B₁

by Zhuo Chen, Rui Chen, Xin Ma, Wenzi Wu, Qixin Huang, Wenxin Ye, Chulong Wu, Bin Yao, Jianhong Xu and Lichun Qian

Toxins 2024, 16(12), 517; https://doi.org/10.3390/toxins16120517 - 29 Nov 2024

Abstract

Aflatoxin B₁ is a prevalent secondary hazardous metabolite generated by fungus present in feed ingredients and the surrounding environment: enzymes are currently being recognized as an efficient and promising approach to reducing the associated risks. The objective of this study was to [...] Read more.

Aflatoxin B₁ is a prevalent secondary hazardous metabolite generated by fungus present in feed ingredients and the surrounding environment: enzymes are currently being recognized as an efficient and promising approach to reducing the associated risks. The objective of this study was to assess the effects of varying doses of enzyme complexes on several parameters in laying hens that were exposed to aflatoxin. During an 8-week experiment, a total of 288 Yukou Jingfen No.6 laying hens were placed into four groups. These groups included a group treated with toxins (CON group) and groups supplemented with compound enzyme complexes at doses of 250 g/t (E1 group), 500 g/t (E2 group), and 1000 g/t (E3 group). The E2 and E3 groups exhibited a statistically significant 2.6% increase in egg production rate compared to the CON group (p < 0.05). In addition, the E2 group showed significant improvements in both the feed-to-egg ratio and egg weight (p < 0.05). In addition, the E2 and E3 groups showed improved hutch unit and egg white height compared to the control group (p < 0.05). The E2 and E3 groups showed a substantial rise in liver health indicators, namely serum alanine transaminase (ALT) and alkaline phosphatase (ALP) activity. On the other hand, malondialdehyde (MDA) was lowered, and total superoxide dismutase (T-SOD) and total antioxidant capacity (T-AOC) were raised. These findings were statistically significant (p < 0.05). The E2 and E3 groups showed notable enhancements in intestinal morphology, as evidenced by a rise in villus height and a decrease in crypt depth in all segments of the intestine (p < 0.05). Furthermore, analysis of 16S rRNA sequencing revealed that these participants had a higher prevalence and variety of microorganisms in their gut microbiota. More precisely, there was a significant rise in the abundance of Bacteroidota and a decline in Firmicutes at the level of the phylum. In general, the inclusion of the enzyme complex had advantageous impacts on performance, egg quality, intestinal morphology, intestinal barrier function, and intestinal flora in laying hens. Our results indicate that toxin-degrading enzymes, when used as feed additives, play a significant role in mitigating AFB₁ contamination in diets and improving the production performance of laying hens. Full article

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16 pages, 2443 KiB

Open AccessArticle

Aflatoxin Contamination of Various Staple Foods from Angola and Mozambique

by Cláudio Matusse, Zelda Lucamba, João Bila, Custódia Macuamule, Ana Sampaio, Sandra Afonso, Armando Venâncio and Paula Rodrigues

Toxins 2024, 16(12), 516; https://doi.org/10.3390/toxins16120516 - 29 Nov 2024

Abstract

Aflatoxins constitute a significant risk in staple foods produced in African countries. This research aimed to analyze the total aflatoxin (AFT) contamination of various staple foods in Angola and Mozambique. A total of 233 samples of corn, peanuts, beans, rice, and cassava flour [...] Read more.

Aflatoxins constitute a significant risk in staple foods produced in African countries. This research aimed to analyze the total aflatoxin (AFT) contamination of various staple foods in Angola and Mozambique. A total of 233 samples of corn, peanuts, beans, rice, and cassava flour collected from farmers or local markets from the province of Cuanza Sul, Angola, and the provinces of Gaza and Inhambane, South Mozambique, were analyzed for the presence of AFT using the lateral flow strip method via AgraStrip^® Pro WATEX^® (Romer). The results showed that, from all matrices, the highest incidence and level of AFT were found in corn produced in Mozambique, with medians ranging from 6.5 to 66.5 µg/kg, with the samples showing values as high as 9200 µg/kg. Levels higher than the maximum admissible levels recommended by the Codex Alimentarius Commission for cereals and pulses (15 µg/kg) were observed in up to 90% of the corn samples, depending on the province. Corn produced in Angola showed lower amounts of AFT, with medians ranging from 1.2 to 7.7 µg/kg. Considering the maximum admissible levels for AFT recommended by the European Commission and the Codex Alimentarius Commission for cereals and pulses, the level of AFT contamination in staple food produced and consumed in the studied provinces is high and constitutes a public health risk for the population. Therefore, risk mitigation strategies are urgently needed. Full article

(This article belongs to the Section Mycotoxins)

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14 pages, 1843 KiB

Open AccessArticle

Sensitive Aflatoxin M1 Detection in Milk by ELISA: Investigation of Different Assay Configurations

by Dimitra Kourti, Michailia Angelopoulou, Panagiota Petrou and Sotirios Kakabakos

Toxins 2024, 16(12), 515; https://doi.org/10.3390/toxins16120515 - 29 Nov 2024

Abstract

Aflatoxin M1 (AFM1) exposure through dairy products is associated with adverse health effects, including hepatotoxicity and carcinogenicity. Therefore, the AFM1 presence in milk and dairy products is strictly regulated. In this context, the current work focuses on the investigation of different competitive enzyme [...] Read more.

Aflatoxin M1 (AFM1) exposure through dairy products is associated with adverse health effects, including hepatotoxicity and carcinogenicity. Therefore, the AFM1 presence in milk and dairy products is strictly regulated. In this context, the current work focuses on the investigation of different competitive enzyme immunoassay configurations for the determination of AFM1 in milk with high sensitivity and short assay duration. Amongst the configurations tested, the one based on incubation of the anti-AFM1 specific antibody along with the calibrators/samples and a biotinylated conjugate of AFM1 with bovine serum albumin (BSA) in microwells coated with a secondary antibody provided a six-fold lower detection limit than the configuration involving immobilized AFM1-BSA conjugate and liquid phase antibody. The detection limit achieved was 5.0 pg/mL, with a dynamic range of up to 2.0 ng/mL. The assay was repeatable with intra- and inter-assay coefficients of variations lower than 3.2% and 6.5%, respectively, and accurate with recovery values from 87.5 to 108%. Moreover, the assay was completed in 1.5 h. The excellent analytical characteristics and short analysis time make the proposed assay suitable for use by the food industry. Furthermore, the proposed configuration could be employed to enhance the detection sensitivity of competitive immunoassays for other low-molecular-weight analytes. Full article

(This article belongs to the Section Mycotoxins)

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