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Toxins
Volume 17
Issue 3
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Toxins, Volume 17, Issue 3 (March 2025) – 51 articles

Cover Story (view full-size image): Paralytic shellfish poisoning is a threat to human health caused by the consumption of shellfish contaminated with toxins of the saxitoxin class. To protect human health, the toxicity of the compounds must be known, and an appropriate method must be used for screening shellfish prior to sale. This review details methods used in biotoxin research highlighting the strengths and weaknesses of each approach. The accurate determination of toxin concentrations can be achieved using analytical methods employing toxicity equivalence factors derived from oral animal toxicity data. Although this level of accuracy cannot be achieved using in vitro assays, these methods have great utility for screening purposes. The way that different countries around the world employ the various techniques to assess the risk posed by shellfish products is discussed. View this paper
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14 pages, 888 KiB  
Article
Snake Venom Makeover: Age-Dependent Variations in Procoagulant Biochemistry of Egyptian Saw-Scaled Viper (Echis pyramidum pyramidum) Venom
by Alex Barker, Lee Jones, Lachlan A. Bourke, Lorenzo Seneci, Abhinandan Chowdhury, Aude Violette, Rudy Fourmy, Raul Soria, Matt Aldridge and Bryan G. Fry
Toxins 2025, 17(3), 149; https://doi.org/10.3390/toxins17030149 - 19 Mar 2025
Viewed by 2122
Abstract
Echis species (saw-scaled vipers) are WHO Category 1 medically significant venomous snakes with potent procoagulant venoms, which cause lethal venom-induced consumptive coagulopathy in human victims. Despite clinical presentations of bites varying significantly between individuals within the same species, the contribution of age-related changes [...] Read more.
Echis species (saw-scaled vipers) are WHO Category 1 medically significant venomous snakes with potent procoagulant venoms, which cause lethal venom-induced consumptive coagulopathy in human victims. Despite clinical presentations of bites varying significantly between individuals within the same species, the contribution of age-related changes in the venom biochemistry has not been investigated. This study investigated the ontogenetic changes in Echis pyramidum pyramidum venom and its impact on therapeutic efficacy. The efficacy of various antivenoms (Echitab, Echitab+ ICP, Inosan MENA, Inosan Pan African, and SAVP-Echis) was tested against both venom phenotypes. While both neonate and adult venoms were procoagulant, there were differences in the underlying biochemistry. Neonate venom was found to potently pathophysiologically activate Factor VII and Factor X, and to a lesser degree Factor XII. In contrast, adult venom was a slower clotter, less potent in activating FVII, equipotent with neonate venom on FXII, and inactive on FX. This is the first documentation of FVII and FXII activation for any Echis venom. The significant ontogenetic toxicological variations in Echis species were shown to impact antivenom efficacy. Among the tested antivenoms, SAVP-Echis was the most effective against both venom phenotypes, with adult venom being better neutralized. These findings suggest the need for a reconsideration of venom mixture selection in antivenom production through the inclusion of neonate venom. Additionally, the results indicate differential ontogenetic predatory ecology, providing a foundation for future natural history investigations. Full article
(This article belongs to the Special Issue Snake Bite and Related Injury)
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12 pages, 1393 KiB  
Article
Incidence of Dysphagia and Comorbidities in Patients with Cervical Dystonia, Analyzed by Botulinum Neurotoxin Treatment Exposure
by Richard L. Barbano, Bahman Jabbari, Marjan Sadeghi, Ahunna Ukah, Emma Yue, Kimberly Becker Ifantides, Nuo-Yu Huang and David Swope
Toxins 2025, 17(3), 148; https://doi.org/10.3390/toxins17030148 - 19 Mar 2025
Viewed by 339
Abstract
Dysphagia is prevalent in patients with cervical dystonia (CD) and is a potential adverse event in patients treated with botulinum neurotoxin (BoNT) for CD. Real-world studies may provide a better understanding of the incidence and potential risk factors of dysphagia after BoNT administration. [...] Read more.
Dysphagia is prevalent in patients with cervical dystonia (CD) and is a potential adverse event in patients treated with botulinum neurotoxin (BoNT) for CD. Real-world studies may provide a better understanding of the incidence and potential risk factors of dysphagia after BoNT administration. This retrospective cohort study used longitudinal patient-level data from Optum’s de-identified Market Clarity Data to evaluate rates of dysphagia in patients with CD exposed and unexposed to BoNT. Patients ≥18 years of age with ≥2 CD diagnoses ≥30 days apart during the study period (1 January 2017–30 September 2021) who had ≥180 days of continuous health plan enrollment prior to the cohort entry date (first CD diagnosis) were included. Overall, the mean (SD) age of all CD patients (Cohort 1; N = 81,884) was 54.00 (16.21) years, and they were mostly female (67.9%) and white (76.96%). BoNT-Exposed patients (Cohort 2; N = 19,244) had a higher incidence of dysphagia (16.3%) and comorbid conditions when compared with BoNT-Unexposed patients (Cohort 3; N = 61,154 [12.1%]). Overall, patients with pre-existing dysphagia, other dystonias, and comorbid neurologic conditions at baseline also had higher proportions of dysphagia. This real-world analysis indicates that comorbid conditions predispose patients with CD to a greater dysphagia risk during treatment. Full article
(This article belongs to the Special Issue Advances in the Treatment of Movement Disorders with Botulinum Toxins)
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9 pages, 865 KiB  
Article
The Effect of Micro-Focused Ultrasound Treatment on Intradermal Botulinum Toxin Type A Injection
by Sarawin Harnchoowong, Natthachat Jurairattanaporn and Vasanop Vachiramon
Toxins 2025, 17(3), 147; https://doi.org/10.3390/toxins17030147 - 19 Mar 2025
Viewed by 680
Abstract
Botulinum toxin type A (BoNT-A) injection and micro-focused ultrasound with visualization (MFU-V) are becoming increasingly popular for various esthetic conditions. However, performing MFU-V subsequently to BoNT-A injection may diminish the efficacy of BoNT-A. Previous reports have indicated the impact of various energy-based devices [...] Read more.
Botulinum toxin type A (BoNT-A) injection and micro-focused ultrasound with visualization (MFU-V) are becoming increasingly popular for various esthetic conditions. However, performing MFU-V subsequently to BoNT-A injection may diminish the efficacy of BoNT-A. Previous reports have indicated the impact of various energy-based devices on BoNT-A. Nevertheless, the influence of MFU-V on BoNT-A has yet to be investigated. Thus, this study aims to evaluate the effect of MFU-V on BoNT-A injection and to determine the optimal interval between each treatment. A randomized controlled study was conducted on 15 subjects. Each participant was assigned to receive four sites of intradermal BoNT-A injection on their forehead. Following BoNT-A injection, these locations were randomized to receive either no MFU-V treatment or further treatment with MFU-V (superficial transducer, 10.0 MHz, 1.5 mm) on the same day, Day 7, or Day 14. On Day 28 following injection, the anhidrosis area was measured using the iodine starch test to objectively evaluate the result. In comparison to the control site (1.10 cm2), the anhidrotic area was significantly smaller in all MFU-V treated sites (0.74 cm2 in immediate MFU-V treatment, p < 0.001; 0.90 cm2 in MFU-V Day 7, p = 0.005; 0.93 cm2 in MFU-V Day 14, p = 0.021). There were no serious and esthetic complications reported in our study. In conclusion, MFU-V with a superficial depth transducer significantly reduced the efficacy of intradermal BoNT-A injection, especially within two weeks following BoNT-A injection. After BoNT-A injection, we recommend MFU-V treatment should be avoided for at least two weeks. Further study is required to evaluate the optimal interval between these two treatments. Full article
(This article belongs to the Section Bacterial Toxins)
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22 pages, 552 KiB  
Article
Effects of a Multicomponent Mycotoxin Detoxifying Agent on Health and Performance of Weaned Pigs Under Combined Dietary Exposure to Deoxynivalenol (DON) and Zearalenone (ZEN)
by Jog Raj, Panagiotis Tassis, Klaus Männer, Hunor Farkaš, Zdenka Jakovčević and Marko Vasiljević
Toxins 2025, 17(3), 146; https://doi.org/10.3390/toxins17030146 - 19 Mar 2025
Viewed by 506
Abstract
The aim of the present study was to evaluate the efficacy of a multicomponent mycotoxin detoxifying agent (MMDA, MYCORAID, Patent Co, Mišićevo, Serbia) in weaned pigs receiving contaminated feed with deoxynivalenol (DON) and zearalenone (ZEN). In total, 168 pigs were equally allocated in [...] Read more.
The aim of the present study was to evaluate the efficacy of a multicomponent mycotoxin detoxifying agent (MMDA, MYCORAID, Patent Co, Mišićevo, Serbia) in weaned pigs receiving contaminated feed with deoxynivalenol (DON) and zearalenone (ZEN). In total, 168 pigs were equally allocated in four experimental groups from day 25 to day 66 of age. The T1 group received feed without mycotoxins or MMDA. The pigs in group T2 received contaminated feed (CF) with 1.5 mg of DON/kg feed and 0.9 mg of ZEN/kg feed for the first two weeks and 1.2 mg of DON/kg feed and 0.9 mg of ZEN/kg feed for the rest of the trial period, without the addition of MMDA. Groups T3 and T4 received the CF with the addition of 1.5 g of MMDA/kg feed (T3), or 3 g of MMDA/kg feed (T4). Performance parameters, stress, and inflammatory biomarkers, as well as mycotoxin residues in liver, kidney, and muscle tissue were assessed. The results demonstrated improved average daily gain (ADG) and feed conversion ratio (FCR) along with reduced DON residues in kidney samples in groups T3 and T4 when compared with the T2 group. Although a typical dose–response relationship was not present in all parameter alterations, the results of the study proved the efficacy of the test product with improved growth performance and reduced mycotoxins absorption under the concurrent DON and ZEN exposure conditions and supported its use as a mitigating tool against mycotoxicosis under field conditions. Full article
(This article belongs to the Special Issue Mycotoxins in Farm Animals: Health Disorders and Preventive Strategies)
15 pages, 8466 KiB  
Article
Nafamostat Mesylate Regulates Glycosylation to Alleviate Aristolochic Acid Induced Kidney Injury
by Pei Xie, Huijun Liu, Xingli Huo, Junlong Chen, Yu Li, Yu Huang and Zongning Yin
Toxins 2025, 17(3), 145; https://doi.org/10.3390/toxins17030145 - 18 Mar 2025
Viewed by 396
Abstract
Acute kidney injury (AKI) is a condition with a poor prognosis, exacerbated by the lack of effective therapeutic options and inadequately understood underlying mechanisms. Glycosylation, a post-translational modification of proteins, is essential for maintaining protein stability and function, and its dysregulation leads to [...] Read more.
Acute kidney injury (AKI) is a condition with a poor prognosis, exacerbated by the lack of effective therapeutic options and inadequately understood underlying mechanisms. Glycosylation, a post-translational modification of proteins, is essential for maintaining protein stability and function, and its dysregulation leads to protein misfolding and amyloid aggregation. Glycosylation dynamics are implicated in several pathologies, including inflammation, cancer, and AKI, highlighting the therapeutic potential of regulating glycosylation and preventing aggregation in AKI treatment. This study investigates the effect of nafamostat mesylate (NM) on protein glycosylation and amyloid aggregation in vivo. Using optical spectroscopy and other analytical techniques, we demonstrate that NM restores glycosylation levels and inhibits protein aggregation in aristolochic-acid-induced acute kidney injury. The mechanism likely involves enzymatic modulation that corrects hypoglycosylation and prevents amyloid aggregation, promoting proper protein folding and enhancing its stability. These findings suggest that NM may provide a novel therapeutic strategy for AKI and other glycosylation-related diseases, underscoring the potential for early intervention and treatment of these conditions. Full article
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22 pages, 5899 KiB  
Article
Ablation of Gut Microbiota Alleviates DON-Induced Neurobehavioral Abnormalities and Brain Damage in Mice
by Yujing Cui, Samuel Kumi Okyere, Haoyue Guan, Zixuan Hua, Youtian Deng, Huidan Deng and Junliang Deng
Toxins 2025, 17(3), 144; https://doi.org/10.3390/toxins17030144 - 18 Mar 2025
Viewed by 381
Abstract
Background: Deoxynivalenol (DON) poses a threat to animal and human health, particularly causing damage to the nervous system. Intestinal flora can regulate the nervous system through the gut–brain axis; however, there is currently a lack of evidence on the effect of changing the [...] Read more.
Background: Deoxynivalenol (DON) poses a threat to animal and human health, particularly causing damage to the nervous system. Intestinal flora can regulate the nervous system through the gut–brain axis; however, there is currently a lack of evidence on the effect of changing the intestinal flora on the damage to the nervous system caused by DON. Therefore, this study aims to investigate the effect of gut microbiota ablation on neurotoxicity induced by exposure to deoxynivalenol. Methods: One hundred-twenty (120) specific pathogen-free (SPF) male C57BL/6j mice were randomly divided into four groups (control group, microbiota-uncleaned group + 5 mg/kg/BW DON, microbiota-cleared group, and microbiota-cleared group + 5 mg/kg/BW DON). The open field and Morris behavior tests were used to evaluate behavior changes after DON exposure. After 14 days of treatment, the mice were euthanized and brain tissues were collected for further analysis. Results: The tests showed that DON exposure led to anxiety and decreased learning ability in mice with no gut microbiota ablation. We also observed pathological changes including neuronal shrinkage, degeneration, and cortical edema in the mice with no microbiota ablation after DON exposure. In addition, the protein and mRNA levels of tight junction proteins and anti-inflammatory factors were decreased in the mice with no microbiota ablation after DON exposure compared with mice with ablated microbiota. Conclusions: We concluded that the presence of microbiota plays a key role in the neurotoxicity induced by DON; thus, ablation of the intestinal microbiota can effectively improve brain damage caused by DON. Full article
(This article belongs to the Special Issue Mycotoxins in Farm Animals: Health Disorders and Preventive Strategies)
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25 pages, 1685 KiB  
Article
Cytotoxic Profiles of Beauvericin, Citrinin, Moniliformin, and Patulin and Their Binary Combinations: A Literature-Based Comparison and Experimental Validation in SH-SY5Y Cells
by Claudia Moyano-López, Luna Bridgeman, Cristina Juan and Ana Juan-García
Toxins 2025, 17(3), 143; https://doi.org/10.3390/toxins17030143 - 17 Mar 2025
Viewed by 456
Abstract
Mycotoxins are toxic compounds found in food and feed that pose significant risks to human and animal health. This work reviews recent studies on the cytotoxic effects of four mycotoxins: beauvericin (BEA), citrinin (CTN), moniliformin (MON), and patulin (PAT) in various cell lines. [...] Read more.
Mycotoxins are toxic compounds found in food and feed that pose significant risks to human and animal health. This work reviews recent studies on the cytotoxic effects of four mycotoxins: beauvericin (BEA), citrinin (CTN), moniliformin (MON), and patulin (PAT) in various cell lines. Additionally, an experimental study evaluates the effects of these mycotoxins and their binary combinations on human neuroblastoma cells (SH-SY5Y) after 24 and 48 h of exposure using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. This analysis is driven by the additional risks posed by the frequent occurrence of these combinations in agricultural and food products, as well as the lack of studies addressing their effects, interactions, and regulatory frameworks. This research focuses on comparing the cytotoxicity data obtained in the SH-SY5Y cell line with previously reported findings in the literature for other cell lines exposed to BEA, CTN, MON, and PAT, individually and in binary combination. The literature highlights significant scientific interest in understanding the cytotoxic effects of these mycotoxins, with findings varying based on exposure time and concentration. Experimentally, PAT demonstrated the highest toxicity in SH-SY5Y cells, while MON was the least toxic. Among combinations, BEA + MON and CTN + PAT showed the greatest reduction in cell viability. However, medium inhibitory concentration (IC50) values were not reached for most combinations involving MON, reflecting its lower potency under the studied conditions. These findings underscore the importance of further investigation and enhanced regulations to address the health risks posed by mycotoxins, as their cytotoxic effects remain a pressing issue in food safety. Full article
(This article belongs to the Special Issue Biomonitoring of Mycotoxins the Silent Invaders, Their Subtle Assault on Human and Animal Health)
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15 pages, 256 KiB  
Article
Long-Term Improvement of Gait Kinematics in Young Children with Cerebral Palsy Treated with Botulinum Toxin Injections and Integrated/Intensive Rehabilitation: A 5-Year Retrospective Observational Study
by Weronika Pyrzanowska, Magdalena Chrościńska-Krawczyk and Marcin Bonikowski
Toxins 2025, 17(3), 142; https://doi.org/10.3390/toxins17030142 - 15 Mar 2025
Viewed by 493
Abstract
Introduction: Patients with cerebral palsy (CP) present mobility limitations that alter their activity and participation in social life. This study aimed to assess changes in gait kinematic measurements using the Observational Gait Scale (OGS) and preselected parameters related to the foot, knee, and [...] Read more.
Introduction: Patients with cerebral palsy (CP) present mobility limitations that alter their activity and participation in social life. This study aimed to assess changes in gait kinematic measurements using the Observational Gait Scale (OGS) and preselected parameters related to the foot, knee, and hip in children with CP who received repeated BoNT-A injections within a rehabilitation treatment over a five-year follow-up period. Material and methods: This single-center retrospective observational study included 200 consecutive children with bilateral CP (GMFCS I–IV). The five-year follow-up period was analyzed. Patients received between 5 and 10 BoNT-A treatments (mean 7.6 ± 2.3), with total doses per session varying from 20 units/kg to 30 units/kg for ABOBoNT-A and from 10 units/kg to 20 units/kg for OnaBoNT-A. In most cases, multilevel injections were performed, including in the hip flexors and adductors, knee flexors, and foot plantar flexors. Results: The mean age of the patients at the beginning was 32.23 months (±6.96). The OGS score improved in 74.5% and 76.5% of the patients, and deterioration occurred in 8.5% and 7% of patients for the right and left lower extremities, respectively. The changes in the OGS typically ranged from 1 to 4 points. Significant improvements in the knee position at midstance, initial foot contact, foot contact at midstance, timing of heel rise, and knee and hip positions at terminal stance were observed. Conclusions: The data from our retrospective observational study show a significant, long-term, positive effect of integrated treatment on gait kinematics in patients with CP in a homogenous group of young children with bilateral spastic cerebral palsy. Full article
25 pages, 4262 KiB  
Article
Selective Modulation of Osteoclast Function by Bothrops moojeni Venom and Its Fractions: Implications for Therapeutic Targeting in Bone Diseases
by Fernanda D’Amélio, Hugo Vigerelli, Isabel de Fátima Correia Batista, Rodrigo Pinheiro Araldi, Álvaro R. B. Prieto-da-Silva, Daniel Carvalho Pimenta and Irina Kerkis
Toxins 2025, 17(3), 141; https://doi.org/10.3390/toxins17030141 - 15 Mar 2025
Viewed by 497
Abstract
Our study explores the differential effects of Bothrops moojeni venom and its fractions on osteoclast (OC) morphology, function, and osteoclastogenesis. The crude venom and its high-molecular-weight (HMW) fraction disrupt critical OC processes, including F-actin ring formation and mitochondrial distribution, thereby impairing bone resorption. [...] Read more.
Our study explores the differential effects of Bothrops moojeni venom and its fractions on osteoclast (OC) morphology, function, and osteoclastogenesis. The crude venom and its high-molecular-weight (HMW) fraction disrupt critical OC processes, including F-actin ring formation and mitochondrial distribution, thereby impairing bone resorption. These components primarily target cytoskeletal integrity and transcription regulation, with the OBSCN gene playing a direct role in OC function. In contrast, the low-molecular-weight (LMW) fraction selectively modulates OCs without significant cytoskeletal alterations. It influences vital cellular signaling pathways, notably through FNIP1 and FNIP2, essential for OC differentiation and function. This suggests a more targeted therapeutic approach with potentially fewer off-target effects. The venom also alters cytokine production, increasing IL-6 and IL-10 levels. Elevated IL-6 levels promote osteoclastogenesis and bone resorption, while IL-10 appears to counterbalance these effects through a regulatory feedback mechanism. Secretome analysis reveals that the crude venom and HMW fraction disrupt proteins involved in membrane trafficking and structural integrity. In contrast, the LMW fraction influences matrix remodeling, energy metabolism, and gene regulation. Gene interaction analysis LMW fraction post-treatment identifies FNIP1 and FNIP2 as critical targets involved in osteoclastogenesis. The observed changes in gene expression, including those related to immune response, energy metabolism, and chromatin remodeling, provide insights into the venom’s impact on bone health. Overall, the LMW fraction shows promise for drug development due to its selective implications and potential for fewer side effects, offering a more precise approach to treating bone diseases. Full article
(This article belongs to the Special Issue Animals Venom in Drug Discovery: A Valuable Therapeutic Tool)
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16 pages, 2122 KiB  
Article
Botulinum Toxin Type A Exerts Direct Trans-Synaptic Action at Bilateral Spinal Nociceptive Circuits
by Dalia Nemanić, Petra Šoštarić, Patrik Meglić, Ivica Matak and Lidija Bach-Rojecky
Toxins 2025, 17(3), 140; https://doi.org/10.3390/toxins17030140 - 14 Mar 2025
Viewed by 503
Abstract
Botulinum toxin type A (BoNT-A) induces a bilateral analgesic effect following unilateral injection in rodent bilateral or mirror pain models. This occurs either by indirect plasticity-related actions, or by the toxin’s direct central action in bilateral spinal circuits. Herein, we aimed to resolve [...] Read more.
Botulinum toxin type A (BoNT-A) induces a bilateral analgesic effect following unilateral injection in rodent bilateral or mirror pain models. This occurs either by indirect plasticity-related actions, or by the toxin’s direct central action in bilateral spinal circuits. Herein, we aimed to resolve this question by assessing the role of trans-synaptic toxin traffic in a bilateral inflammatory pain model. The analgesic effect of the toxin was examined in rats pre-treated with unilateral intraplantar BoNT-A (7 U/kg) and subsequently challenged with bilateral carrageenan-evoked hind-paw inflammation (2%, 50 µL/paw, 6 days post BoNT-A). Specific neutralizing antitoxin injected into the lumbar intrathecal space (2 IU, 24 h post BoNT-A), aimed at preventing the spinal trans-synaptic traffic of BoNT-A, abolished its bilateral analgesic effect. The toxin trans-synaptic effect was associated with reduced c-Fos neuronal activation and BoNT-A-mediated cleavage of synaptosomal-associated protein 25 (SNAP-25) in the bilateral dorsal horn. Here, we showed that, in bilaterally occurring pain, BoNT-A exerts a direct contralateral analgesic action extending beyond the level of the dorsal root ganglion sensory neuron that directly links the hindlimb injection site to the primary sensory region. This points to the crucial role of the toxin’s central trans-synaptic traffic, and its direct action at propriospinal nociceptive circuits in its pain-relieving efficacy. Full article
(This article belongs to the Special Issue Botulinum Toxins: Beyond the SNAP-25 Cleavage and New Insights on Pain Relief Mechanisms)
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16 pages, 4273 KiB  
Review
Mechanism of Mycotoxin Contamination of Medicinal Herbs
by Abdelrahman Elamin and Shohei Sakuda
Toxins 2025, 17(3), 139; https://doi.org/10.3390/toxins17030139 - 14 Mar 2025
Viewed by 533
Abstract
Mycotoxin contamination in medicinal plants can lead to toxicity, reduced therapeutic efficacy, and economic losses. This contamination has emerged as a significant issue, drawing attention from researchers and research centers worldwide. Over recent decades, numerous analytical studies have addressed mycotoxin contamination in these [...] Read more.
Mycotoxin contamination in medicinal plants can lead to toxicity, reduced therapeutic efficacy, and economic losses. This contamination has emerged as a significant issue, drawing attention from researchers and research centers worldwide. Over recent decades, numerous analytical studies have addressed mycotoxin contamination in these herbs, evaluating various methods to determine their presence quantitatively and qualitatively. While several reviews have summarized these studies, they often overlook a comprehensive exploration of the mechanisms and influencing factors of mycotoxin contamination in medicinal herbs. Therefore, this review aims to delve into the mechanisms of aflatoxin and ochratoxin contamination in some of the most widespread medicinal herbs, including jujube fruits, lotus seeds, and licorice roots. The factors influencing these mechanisms were also examined, including the physical composition and maturity stages of the herbs. This review concluded that aflatoxin and ochratoxin A contamination of medicinal herbs involves complex interactions between the herbs’ natural defenses, fungal pathogenicity, chemical composition, physical characteristics, and individual plant differences at various maturity stages. Understanding these mechanisms of contamination, and their association with maturity, nutrient profile, and physical development, advances our comprehension of mycotoxin contamination in medicinal herbs. Full article
(This article belongs to the Special Issue Advances in Mycotoxin Determination: From Risk Assessment to Global Management Strategies)
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13 pages, 2309 KiB  
Article
An Effective Prophylactic and Therapeutic Protection Against Botulinum Type A Intoxication in Mice and Rabbits Using a Humanized Monoclonal Antibody
by Chi Ho Yu, Young-Jo Song, Dong Hyun Song, Hae Eun Joe, Chang-Hwan Kim, Hyungseok Yun, Na Young Kim, Euni Sim, Seong Tae Jeong and Gyeung Haeng Hur
Toxins 2025, 17(3), 138; https://doi.org/10.3390/toxins17030138 - 14 Mar 2025
Viewed by 501
Abstract
Botulinum neurotoxins (BoNTs) are the most potent toxins on Earth and are classified as Category A biological agents. BoNTs lead to paralysis in humans and cause botulism. Antibody therapeutics can effectively treat toxin-mediated infectious diseases. In this study, we generated a pharmaceutical humanized [...] Read more.
Botulinum neurotoxins (BoNTs) are the most potent toxins on Earth and are classified as Category A biological agents. BoNTs lead to paralysis in humans and cause botulism. Antibody therapeutics can effectively treat toxin-mediated infectious diseases. In this study, we generated a pharmaceutical humanized monoclonal antibody (HZ45 mAb) to prevent or treat botulism. HZ45 binds to the heavy chain receptor (HCR) domain of the toxin, preventing the toxin from entering the cell. The mAb was produced using hybridoma technology and phage display. We evaluated HZ45 mAb for the neutralization of BoNT serotype A (BoNT/A) in mice and rabbits. The survival results showed that pretreatment with HZ45 mAb provided 100% protection at a dose of 0.1 mg per mouse against a maximum of 100 LD50 of BoNT/A. To assess the therapeutic efficacy of HZ45 mAb in New Zealand white rabbits (NZWs), a 5 mg dose was administered 4 or 8 h after challenge with 10 LD50. The results indicated that 5 mg of HZ45 could treat the NZWs within 8 h after exposure to 10 LD50 botulinum. Consequently, in an in vivo context, including mice and rabbits, HZ45 mAb could protect against botulinum type A intoxication. Full article
(This article belongs to the Section Bacterial Toxins)
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15 pages, 7503 KiB  
Article
Occurrence of Co-Contamination and Interaction of Multi-Mycotoxins in Dairy Cow Feed in China
by Zuoyin Zhu, Haisheng Cheng, Jie Wang, Junmei Ma, Jianhua Wang, Hongyang Wang, Xinli Zhou and Junhua Yang
Toxins 2025, 17(3), 137; https://doi.org/10.3390/toxins17030137 - 14 Mar 2025
Viewed by 456
Abstract
Co-contamination of multiple mycotoxins in feed has become one of the most important issues in the world. In this study, the characteristics and interactions of co-contamination among 15 mycotoxins were explored in dairy cow feed, including total mixed ration (TMR), silage, maize, and [...] Read more.
Co-contamination of multiple mycotoxins in feed has become one of the most important issues in the world. In this study, the characteristics and interactions of co-contamination among 15 mycotoxins were explored in dairy cow feed, including total mixed ration (TMR), silage, maize, and hay feed. The results showed that four dairy cow feeds were constantly contaminated with mycotoxins, including zearalenone (ZEN), fumonisins (FBs), deoxynivalenol (DON), ochratoxin A (OTA), T-2 toxin (T-2), and aflatoxins (AFs). The contamination level of each mycotoxin was low, but the probability of co-contamination by three or more mycotoxins in one sample was very high. Between DON and aflatoxin B2 (AFB2), between aflatoxin M1 (AFM1) and OTA, between FB2 and aflatoxin B1 (AFB1), between 15-acetyl-deoxynivalenol (15-ADON) and ZEN, and between fumonisin B1 (FB1) and fumonisin B3 (FB3), and between aflatoxin M2 (AFM2) and aflatoxin G2 (AFG2), there were significant and strong correlations. Among the four typical feed samples, the combinations DON + ZEN, DON + FB1, FB1 + ZEN, OTA + ZEN, DON + 3-acetyl-deoxynivalenol (3-ADON), 3-ADON + ZEN, T-2 + ZEN, fumonisin B2 (FB2) + ZEN, and DON + FB3 had higher interaction rates than the other combinations (≥43.75%). Our study not only reveals that co-contamination with multiple mycotoxins is relatively common in dairy cow feed but also highlights the significant correlations between various mycotoxins and assesses the likelihood of their interactions. These findings are crucial for ensuring feed safety and safeguarding animal health. Full article
(This article belongs to the Section Mycotoxins)
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31 pages, 2052 KiB  
Systematic Review
Innovations in Snake Venom-Derived Therapeutics: A Systematic Review of Global Patents and Their Pharmacological Applications
by Diana Carolina Zona Rubio, Diana Marcela Aragón and Izabel Almeida Alves
Toxins 2025, 17(3), 136; https://doi.org/10.3390/toxins17030136 - 14 Mar 2025
Viewed by 1222
Abstract
Active compounds from natural sources, particularly snake venoms, are crucial for pharmaceutical development despite challenges in drug discovery. Snake venoms, historically used for medicinal purposes, contain bioactive peptides and enzymes that show therapeutic potential for conditions such as arthritis, asthma, cancer, chronic pain, [...] Read more.
Active compounds from natural sources, particularly snake venoms, are crucial for pharmaceutical development despite challenges in drug discovery. Snake venoms, historically used for medicinal purposes, contain bioactive peptides and enzymes that show therapeutic potential for conditions such as arthritis, asthma, cancer, chronic pain, infections and cardiovascular diseases. The objective of this study was to examine pharmacological and biomedical innovations by identifying the key research trends, the most studied snake species, and their therapeutic applications. A systematic review of patents related to snake venoms was conducted using the European Patent Office database, Espacenet, covering 2014 to mid-2024. The search employed the keyword “venom,” applying IPC classification A61K38/00, resulting in 31 patents after screening. A PubMed survey on “snake venom derivatives innovations” was conducted to compare the scientific literature volume with the identified patents. This review highlights the therapeutic potential of snake venom-derived products for coagulation disorders, cancer, inflammation, and pain management. Despite challenges in pharmacokinetics and venom variability, advancements in biotechnology offer promise for personalized therapies. The future of snake venom-based treatments appears promising for addressing complex medical conditions. Full article
(This article belongs to the Special Issue Animals Venom in Drug Discovery: A Valuable Therapeutic Tool)
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22 pages, 629 KiB  
Article
Investigation into Paralytic Shellfish Toxins and Microcystins in Seabirds from Portugal
by Lucía Soliño, Andrew D. Turner, Begoña Ben-Gigirey, Ryan P. Alexander, Karl J. Dean, Robert G. Hatfield, Benjamin H. Maskrey and María V. Mena Casero
Toxins 2025, 17(3), 135; https://doi.org/10.3390/toxins17030135 - 13 Mar 2025
Viewed by 482
Abstract
Microalgae form the basis of marine food webs, essential in sustaining top predators including seabirds. However, certain species of microalgae synthesize biotoxins, which can accumulate in shellfish and fish and may cause harm to marine animals feeding on them. Toxins produced by dinoflagellates [...] Read more.
Microalgae form the basis of marine food webs, essential in sustaining top predators including seabirds. However, certain species of microalgae synthesize biotoxins, which can accumulate in shellfish and fish and may cause harm to marine animals feeding on them. Toxins produced by dinoflagellates have been previously observed to be poisonous to seabirds. Also, in freshwater and brackish habitats, cyanobacteria have caused bird mortality events. In this work, we analyze the prevalence of six families of biotoxins (paralytic shellfish toxins (PSTs), microcystins (MCs), anatoxins, amnesic shellfish toxins (ASTs), cylindrospermopsin, and tetrodotoxins (TTXs)) in 340 samples from 193 wild birds admitted to a wildlife rehabilitation centre in south Portugal. Furthermore, we consider the clinical picture and signs of 17 birds that presented quantifiable levels of biotoxins in their tissues. The relationship between toxin burdens and the symptomatology observed, as well as possible biotoxin sources, are discussed. Based on previously published research data, we conclude that, in these birds, the biotoxins are unlikely to be the only cause of death but might contribute to some extent to a reduction in birds’ fitness. Full article
(This article belongs to the Special Issue Harmful Algal Blooms in Waters: Characterization, Monitoring and Management)
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17 pages, 1729 KiB  
Article
Sting Stories: Firsthand Experiences of Fish Envenomation Through a Small-Scale Questionnaire
by Richard J. Harris, Silvia L. Saggiomo, Gillian Paxton and Cherie A. Motti
Toxins 2025, 17(3), 134; https://doi.org/10.3390/toxins17030134 - 13 Mar 2025
Viewed by 527
Abstract
Stings from venomous bony and cartilaginous fishes are known to cause extreme pain in humans, and with changing migratory patterns and distributions due to climate change, human interactions with venomous fishes may increase. Therefore, developing a better understanding of venomous fish stings and [...] Read more.
Stings from venomous bony and cartilaginous fishes are known to cause extreme pain in humans, and with changing migratory patterns and distributions due to climate change, human interactions with venomous fishes may increase. Therefore, developing a better understanding of venomous fish stings and the associated pain can provide better solutions for first aid and treatments, particularly in areas or within populations with a higher risk of being stung. Using the results from an online questionnaire, this study discusses the perspectives of 121 people with direct experience of fish stings, exploring the contexts in which fish stings occurred, their firsthand experiences of pain, sting pathophysiology, experiences with medical treatments, and the long-term consequences of fish stings. This small-scale survey has proved successful for the exploration of fish sting experiences, and as such, an approach of this nature should be considered to better understand victim’s experiences with other painful animal stings. Full article
(This article belongs to the Special Issue Venoms of Aquatic Organisms: Biochemistry, Evolution, and Future Perspectives)
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10 pages, 507 KiB  
Article
Efficacy Remaining at Time of Requested Re-Treatment for Cervical Dystonia: A Potential New Treatment Paradigm with DaxibotulinumtoxinA
by Aaron Ellenbogen, Robert A. Hauser, Atul T. Patel, Peter McAllister, Todd M. Gross, Rashid Kazerooni, Conor J. Gallagher and David A. Hollander
Toxins 2025, 17(3), 133; https://doi.org/10.3390/toxins17030133 - 12 Mar 2025
Viewed by 683
Abstract
The therapeutic efficacy remaining from prior treatments with botulinum toxins (BoNTs) when cervical dystonia (CD) patients prefer to be re-treated has not been well characterized. Here, we assessed the residual therapeutic efficacy of BoNT injections at the time of a patient-desired re-treatment. In [...] Read more.
The therapeutic efficacy remaining from prior treatments with botulinum toxins (BoNTs) when cervical dystonia (CD) patients prefer to be re-treated has not been well characterized. Here, we assessed the residual therapeutic efficacy of BoNT injections at the time of a patient-desired re-treatment. In pivotal trials for daxibotulinumtoxinA (DAXI) in CD, subjects could request re-treatment before returning to pre-treatment symptom levels (defined as ≤20% of peak efficacy remaining). In this post hoc analysis of the Phase 3 ASPEN-OLS trial, the median percent efficacy remaining (based on change in TWSTRS total score) was determined in subjects who requested re-injection before returning to pre-treatment symptoms. Dysphagia and muscle weakness were evaluated in patients requesting re-treatment with efficacy remaining, relative to those waiting to return to baseline. There were 264 (28.7% of 920 total treatments) patient requests for re-treatment before returning to pre-treatment status across the study. The median percent efficacy remaining at the time of requested re-injection was 45.5%, which corresponded to a median of 16.0 weeks (range 10.9–40.3) post-treatment. The rates of dysphagia (≤4.9%) and muscle weakness (≤6.8%) were low and were not significantly different in those who waited for return to pre-treatment symptom status versus subjects who requested re-injection with efficacy remaining. A significant proportion of CD patients wished to be re-treated with efficacy still remaining from prior BoNT injections as early symptoms re-emerged. With the overall clinical profile of DAXI, physicians can safely provide individualized treatment regimens based on the treatment goals or symptomatic needs of their patients. Full article
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19 pages, 2471 KiB  
Article
Real-Time CO2 Production Monitoring in Stored Oats as an Indicator of Type A Trichothecenes and Ochratoxin A Contamination Under Simulated Environmental Conditions
by Abimbola Oluwakayode, Michael Sulyok, Franz Berthiller, Carol Verheecke-Vaessen, Rudolf Krska and Angel Medina
Toxins 2025, 17(3), 132; https://doi.org/10.3390/toxins17030132 - 11 Mar 2025
Viewed by 781
Abstract
Grain industries are interested in an integrated approach to in-silo grain quality and safety management using carbon dioxide (CO2) measurement with temperature and moisture monitoring. Our study investigates if CO2 production could predict mycotoxin production (T-2 toxin, HT-2 toxin, its [...] Read more.
Grain industries are interested in an integrated approach to in-silo grain quality and safety management using carbon dioxide (CO2) measurement with temperature and moisture monitoring. Our study investigates if CO2 production could predict mycotoxin production (T-2 toxin, HT-2 toxin, its glucoside, and ochratoxin A (OTA)) and identify storage conditions exceeding legislative limits in stored oats for the first time. The influence of water activity (aw) levels (0.70–0.95 aw), temperature (15 and 20 °C), and storage duration on (a) Fusarium populations, (b) CO2 respiration rates (RRs), and (c) mycotoxin concentrations in stored oats was examined. One hundred and twenty samples were analysed for multiple mycotoxins by LC-MS/MS. Substantial differences were found in the RRs of oats at ≥0.90 aw at both temperatures. A moderate positive correlation between CO2 and mycotoxins was noticed and mycotoxins exceeded their limits at ≥0.90 aw (22% moisture content) when RR ≥ 25 µg CO2 kg−1 h−1. This knowledge forms the basis for developing decision support systems for improving oats’ storage management. Full article
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23 pages, 6311 KiB  
Article
Green-Engineered Montmorillonite Clays for the Adsorption, Detoxification, and Mitigation of Aflatoxin B1 Toxicity
by Johnson O. Oladele, Xenophon Xenophontos, Gustavo M. Elizondo III, Yash Daasari, Meichen Wang, Phanourios Tamamis, Natalie M. Johnson and Timothy D. Phillips
Toxins 2025, 17(3), 131; https://doi.org/10.3390/toxins17030131 - 11 Mar 2025
Viewed by 607
Abstract
Dietary and environmental exposure to aflatoxins via contaminated food items can pose major health challenges to both humans and animals. Studies have reported the coexistence of aflatoxins and other environmental toxins. This emphasizes the urgent need for efficient and effective mitigation strategies for [...] Read more.
Dietary and environmental exposure to aflatoxins via contaminated food items can pose major health challenges to both humans and animals. Studies have reported the coexistence of aflatoxins and other environmental toxins. This emphasizes the urgent need for efficient and effective mitigation strategies for aflatoxins. Previous reports from our laboratory have demonstrated the potency of the green-engineered clays (GECs) on ochratoxin and other toxic chemicals. Therefore, this study sought to investigate the binding and detoxification potential of chlorophyll (CMCH and SMCH) and chlorophyllin (CMCHin and SMCHin)-amended montmorillonite clays for aflatoxin B1 (AFB1). In addition to analyzing binding metrics including affinity, capacity, free energy, and enthalpy, the sorption mechanisms of AFB1 onto the surfaces of engineered clays were also investigated. Computational and experimental studies were performed to validate the efficacy and safety of the clays. CMCH showed the highest binding capacity (Qmax) of 0.43 mol/kg compared to the parent clays CM (0.34 mol/kg) and SM (0.32 mol/kg). Interestingly, there were no significant changes in the binding capacity of the clays at pH2 and pH6, suggesting that the clays can bind to AFB1 throughout the gastrointestinal track. In silico investigations employing molecular dynamics simulations also demonstrated that CMCH enhanced AFB1 binding as compared to parent clay and predicted hydrophobic interactions as the main mode of interaction between the AFB1 and CMCH. This was corroborated by the kinetic results which indicated that the interaction was best defined by chemosorption with favorable thermodynamics and Gibbs free energy (∆G) being negative. In vitro experiments in Hep G2 cells showed that clay treatment mitigated AFB1-induced cytotoxicity, with the exception of 0.5% (w/v) SMCH. Finally, the in vivo results validated the protection of all the clays against AFB1-induced toxicities in Hydra vulgaris. This study showed that these clays significantly detoxified AFB1 (86% to 100%) and provided complete protection at levels as low as 0.1%, suggesting that they may be used as AFB1 binders in feed and food. Full article
(This article belongs to the Special Issue 65 Years On from Aflatoxin Discovery—a Themed Issue in Honor of Professor John D. Groopman)
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14 pages, 2891 KiB  
Article
Can Botulinum Toxin Type E Serve as a Novel Therapeutic Target for Managing Chronic Orofacial Pain?
by Sung-Koog Jung, Yu-Mi Kim, Min-Jeong Jo, Jo-Young Son, Jin-Sook Ju, Min-Kyoung Park, Min-Kyung Lee, Jae-Young Kim, Jeong-Sun Nam and Dong-Kuk Ahn
Toxins 2025, 17(3), 130; https://doi.org/10.3390/toxins17030130 - 10 Mar 2025
Viewed by 636
Abstract
The existing literature offers limited experimental evidence on the role of botulinum neurotoxin type E (BoNT-E) in pain transmission. The present study investigated the antinociceptive effects of subcutaneously administered BoNT-E in chronic orofacial pain conditions. This study used orofacial formalin-induced pronociceptive behavior and [...] Read more.
The existing literature offers limited experimental evidence on the role of botulinum neurotoxin type E (BoNT-E) in pain transmission. The present study investigated the antinociceptive effects of subcutaneously administered BoNT-E in chronic orofacial pain conditions. This study used orofacial formalin-induced pronociceptive behavior and complete Freund’s adjuvant (CFA)-induced thermal hyperalgesia as inflammatory pain models in male Sprague Dawley rats. A neuropathic pain model was also developed by causing an injury to the inferior alveolar nerve. Subcutaneously administered BoNT-E (6, 10 units/kg) significantly reduced nociceptive behavior during the second phase of the formalin test compared to that of the vehicle treatment. These doses similarly alleviated thermal hypersensitivity in the CFA-treated rats. Moreover, BoNT-E (6, 10 units/kg) markedly attenuated mechanical allodynia in rats with an inferior alveolar nerve injury. At a dose of 10 units/kg, BoNT-E produced antinociceptive effects that became evident 8 h post-injection and persisted for 48 h. Notably, BoNT-E (10 units/kg) significantly reduced the number of c-fos-immunostained neurons in the trigeminal subnucleus caudalis of rats with an inferior alveolar nerve injury. In comparison, intraperitoneally administered gabapentin (30, 100 mg/kg) demonstrated significant mechanical anti-allodynic effects but exhibited lower analgesic efficacy than that of BoNT-E. These findings highlight the potential of BoNT-E as a therapeutic agent for chronic pain management. Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases (2nd Edition))
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20 pages, 838 KiB  
Review
A Review of Decontamination of Aspergillus spp. and Aflatoxin Control for Grains and Nuts with Atmospheric Cold Plasma
by Miral Javed, Wei Cao, Linyi Tang and Kevin M. Keener
Toxins 2025, 17(3), 129; https://doi.org/10.3390/toxins17030129 - 10 Mar 2025
Viewed by 852
Abstract
Aspergillus spp. and their produced aflatoxins are responsible for contaminating 25–30% of the global food supply, including many grains, and nuts which when consumed are detrimental to human and animal health. Despite regulatory frameworks, Aspergillus spp. and aflatoxin contamination is still a global [...] Read more.
Aspergillus spp. and their produced aflatoxins are responsible for contaminating 25–30% of the global food supply, including many grains, and nuts which when consumed are detrimental to human and animal health. Despite regulatory frameworks, Aspergillus spp. and aflatoxin contamination is still a global challenge, especially in cereal-based matrices and their derived by-products. The methods for reducing Aspergillus spp. and aflatoxin contamination involve various approaches, including physical, chemical, and biological control strategies. Recently, a novel technology, atmospheric cold plasma (ACP), has emerged which can reduce mold populations and also degrade these toxins. ACP is a non-thermal technology that operates at room temperature and atmospheric pressure. It can reduce mold and toxins from grains and seeds without affecting food quality or leaving any chemical residue. ACP is the conversion of a gas, such as air, into a reactive gas. Specifically, an electrical charge is applied to the “working” gas (air) leading to the breakdown of diatomic oxygen, diatomic nitrogen, and water vapor into a mixture of radicals (e.g., atomic oxygen, atomic nitrogen, atomic hydrogen, hydroxyls), metastable species, and ions (e.g., nitrate, nitrite, peroxynitrate). In a cold plasma process, approximately 5% or less of the working gas is ionized. However, cold plasma treatment can generate over 1000 ppm of reactive gas species (RGS). The final result is a range of bactericidal and fungicidal molecules such as ozone, peroxides, nitrates, and many others. This review provides an overview of the mechanisms and chemistry of ACP and its application in inactivating Aspergillus spp. and degrading aflatoxins, serving as a novel treatment to enhance the safety and quality of grains and nuts. The final section of the review discusses the commercialization status of ACP treatment. Full article
(This article belongs to the Special Issue Aspergillus flavus and Aflatoxins (3rd Edition))
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15 pages, 3542 KiB  
Article
Excretion Routes of Okadaic Acid and Dinophysistoxin-2 from Mussels (Mytilus galloprovincialis) and Cockles (Cerastoderma edule)
by Juan Blanco, Noelia Estévez-Calvar and Helena Martín
Toxins 2025, 17(3), 128; https://doi.org/10.3390/toxins17030128 - 9 Mar 2025
Viewed by 603
Abstract
The knowledge of the routes of excretion of the toxins accumulated by molluscs is a key step in designing methods that accelerate depuration. In this work, the excretion route, in mussels and cockles, of the main diarrhetic shellfish poisoning (DSP) toxins in Europe [...] Read more.
The knowledge of the routes of excretion of the toxins accumulated by molluscs is a key step in designing methods that accelerate depuration. In this work, the excretion route, in mussels and cockles, of the main diarrhetic shellfish poisoning (DSP) toxins in Europe (okadaic acid and dinophysistoxin-2) after natural intoxication were studied. During depuration, the amounts of free toxins and their derivatives were quantified in bivalves, faeces, and water. Most toxins (>98%) were excreted through faeces as acyl derivatives (most likely 7-O-acyl esters), independent of the ratio between these derivatives and free toxins in soft tissues. The small proportion of toxins excreted into water mostly constituted the free forms of the toxins. Both species shared the same route even though they contained very different proportions of free toxins in their soft tissues. No substantial changes in this general pattern were observed during the experiment. The esters of fatty acids with 16 carbon atoms were the most abundant in both soft tissues and faeces, but they were not the same in mussels and cockles. Most of the variability in ester proportions can be attributed to the species more than to their differential excretion (water or faeces) suggesting that there are not large differences in the depuration of the different esters. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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22 pages, 6784 KiB  
Article
Transcriptomic Characterization of the Porcine Urinary Bladder Trigone Following Intravesical Administration of Resiniferatoxin: Insights from High-Throughput Sequencing
by Ewa Lepiarczyk, Mateusz Maździarz, Łukasz Paukszto, Agnieszka Bossowska, Mariusz Majewski, Jerzy Kaleczyc, Elżbieta Łopieńska-Biernat, Łukasz Jaśkiewicz, Agnieszka Skowrońska, Mariusz T. Skowroński and Marta Majewska
Toxins 2025, 17(3), 127; https://doi.org/10.3390/toxins17030127 - 9 Mar 2025
Viewed by 839
Abstract
Resiniferatoxin (RTX), a potent capsaicin analog, is being investigated as a therapeutic agent for neurogenic conditions, particularly those affecting bladder control. However, the transcriptomic effects of RTX on the urinary bladder remain largely unexplored. This study aimed to characterize the transcriptomic changes in [...] Read more.
Resiniferatoxin (RTX), a potent capsaicin analog, is being investigated as a therapeutic agent for neurogenic conditions, particularly those affecting bladder control. However, the transcriptomic effects of RTX on the urinary bladder remain largely unexplored. This study aimed to characterize the transcriptomic changes in the porcine urinary bladder trigone region removed seven days post-treatment with intravesical RTX administration (500 nmol per animal in 60 mL of 5% aqueous solution of ethyl alcohol). High-throughput sequencing identified 126 differentially expressed genes (DEGs; 66 downregulated, 60 upregulated), 5 differentially expressed long non-coding RNAs (DELs), and 22 other RNAs, collectively involved in 175 gene ontology (GO) processes. Additionally, differential alternative splicing events (DASes) and single nucleotide variants (SNVs) were detected. RTX significantly modulated signaling pathways related to nerve growth and myelination. Changes in genes associated with synaptic plasticity and neuromodulation were observed, particularly within serotoninergic and cholinergic signaling. RTX altered the expression of immune-related genes, particularly those involved in chemokine signaling and immune regulation. Notably, altered gene expression patterns suggest a potential anti-cancer role for RTX. These findings provide new insights into RTX’s therapeutic effects beyond TRPV1 receptor interactions, filling a critical gap in our understanding of its molecular impact on bladder tissue. Full article
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49 pages, 2741 KiB  
Review
Health and Environmental Impacts of Cyanobacteria and Cyanotoxins from Freshwater to Seawater
by Tamara Villalobos, Benjamín Suárez-Isla and Carlos Garcia
Toxins 2025, 17(3), 126; https://doi.org/10.3390/toxins17030126 - 7 Mar 2025
Viewed by 1335
Abstract
Cyanobacterial harmful algal blooms (cyanoHABs) are a natural phenomenon produced mainly by the interaction between natural and anthropogenic events. CyanoHABs are characterized by the production of cyanotoxins that can have harmful effects on different species within the food web and even affect human [...] Read more.
Cyanobacterial harmful algal blooms (cyanoHABs) are a natural phenomenon produced mainly by the interaction between natural and anthropogenic events. CyanoHABs are characterized by the production of cyanotoxins that can have harmful effects on different species within the food web and even affect human health. Among the most prevalent toxin groups worldwide are microcystins (MCs), anatoxins (ATXs), cylindrospermopsins (CYNs) and nodularins (NODs), which are characterized as toxins with hepatotoxic, neurotoxic, and cytotoxic effects. This review summarizes and analyzes research on the influence of cyanoHABs, the main toxin-producing cyanobacteria and the most prevalent cyanotoxins in freshwater and marine bodies, highlighting their global occurrence, toxicology, and bioaccumulation dynamics in vectors of the food web, and the main cases of acute and chronic intoxications in humans. This review is useful for understanding the dynamics of cyanoHABs’ interaction with the ecosystem and their impact on human health, and how the implementation of a surveillance and management framework for cyanobacteria and cyanotoxins could generate vital information for stakeholders to establish health guidelines on the risks and hazards of cyanoHABs for the ecosystem and humans. Full article
(This article belongs to the Special Issue Advances in Cyanotoxins: Latest Developments in Risk Assessment)
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15 pages, 968 KiB  
Article
Learnings from Separate Aconitum Poisonings in British Columbia and Ontario, Canada in 2022
by Lorraine McIntyre, Stefanie Georgopoulos, Dorianna Simone, Emily Newhouse, JoAnne Fernandes, David A. McVea, Arnold Fok, Ania-Maria McIntyre, Bryn Shurmer, Marie-Claude Gagnon, Michael Chan, Marina Chiaravalloti, Nikita Saha Turna, Debra Kent, Dennis Leong, Katherine Paphitis, Christina Lee and the Outbreak Investigation Teams
Toxins 2025, 17(3), 125; https://doi.org/10.3390/toxins17030125 - 7 Mar 2025
Viewed by 1729
Abstract
Background: Three aconitine poisoning events occurred in two Canadian provinces in 2022: one in British Columbia (BC) and two in Ontario (ON). Aconitine is a potent alkaloid found in several species of the plant Aconitum, containing cardiotoxins and neurotoxins. It is used [...] Read more.
Background: Three aconitine poisoning events occurred in two Canadian provinces in 2022: one in British Columbia (BC) and two in Ontario (ON). Aconitine is a potent alkaloid found in several species of the plant Aconitum, containing cardiotoxins and neurotoxins. It is used in traditional Chinese medicine (TCM) for pain management, and in powdered form, Aconitum is similar in appearance to sand ginger (Kaempferia galanga), which can lead to poisonings from misidentification and mislabeling. Methods: Aconitine poisoning is rare in Canada; here, we compare communications, collaborations, laboratory testing options and actions during investigations. Results: Fourteen cases occurred from the consumption of sand ginger: in BC (n = 2), purchased at an Asian health food store; in ON (n = 11), Kaempferia galanga powder (KGP) spices were used to prepare meals at a restaurant, and in one ON case, KGP was purchased. Traceback found product imported from China contained aconitine levels ranging from 1304 to 5500 ppm. Later investigations revealed mislabeling of Aconitum as KGP from the same imported lot (January 2020). Plant DNA testing found no KGP in any spice packets, including lots not linked to illness, suggestive of adulteration. Conclusion: Method development for aconitine in BC led to an improved response time for testing in ON. BC and ON updated outbreak response protocols and communications. Full article
(This article belongs to the Special Issue Plant Toxin Emergency)
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16 pages, 4035 KiB  
Article
Abiotic Degradation of the Toxin Simplexin by Soil Collected from a Pimelea-Infested Paddock
by Zhi Hung Loh, Natasha L. Hungerford, Diane Ouwerkerk, Athol V. Klieve and Mary T. Fletcher
Toxins 2025, 17(3), 124; https://doi.org/10.3390/toxins17030124 - 6 Mar 2025
Viewed by 601
Abstract
Pimelea poisoning of cattle is caused by the toxin simplexin present in native Pimelea plant species. Surface weathering and burial of Pimelea plant material under soil in Pimelea-infested pastures previously showed simplexin degradation, suggesting soil microbial metabolism and/or abiotic degradation of simplexin [...] Read more.
Pimelea poisoning of cattle is caused by the toxin simplexin present in native Pimelea plant species. Surface weathering and burial of Pimelea plant material under soil in Pimelea-infested pastures previously showed simplexin degradation, suggesting soil microbial metabolism and/or abiotic degradation of simplexin in the field. This current study investigated whether soil from a Pimelea-infested paddock was capable of simplexin degradation in the laboratory. The effects of temperature on isolated simplexin levels and simplexin levels in Pimelea plant material treated with field-collected soil, acid-washed sand or bentonite were determined. Pimelea plant material incubated in field-collected soil at 22 °C for seven days did not show any simplexin degradation. Isolated simplexin preadsorbed to field-collected soil, acid-washed sand or bentonite showed simplexin decrease after one hour of incubation at 100 °C with three breakdown products identified by UPLC-MS/MS, indicating that toxin breakdown can be a heat-induced process rather than a microbial-based metabolism. Decreased simplexin levels were observed in Pimelea plant material mixed with acid-washed sand under similar incubation conditions. Overall, the study showed the field-collected soil did not contain soil microorganisms capable of simplexin metabolism within a short period of time. However, the co-exposure to high temperature resulted in significant abiotic simplexin breakdown, without microorganism involvement, with the product structures suggesting that the degradation was a heat promoted acid hydrolysis/elimination process. Overall, this study demonstrated that simplexin breakdown in the field could be a thermal abiotic process with no indication of microbial involvement. Full article
(This article belongs to the Section Plant Toxins)
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8 pages, 411 KiB  
Communication
Deoxynivalenol Determination Using Innovative Lateral Flow Device Technology
by Halberstadt Delphine, Giorni Paola, Barato Erica and Bertuzzi Terenzio
Toxins 2025, 17(3), 123; https://doi.org/10.3390/toxins17030123 - 5 Mar 2025
Viewed by 576
Abstract
Deoxynivalenol (DON), generally the most widespread mycotoxin in wheat, is regulated by the EU regulation in cereals and cereal-derived products. Its presence can be detected by chromatographic or rapid methods; the latter technique is generally used in control analysis, fulfilling the needs of [...] Read more.
Deoxynivalenol (DON), generally the most widespread mycotoxin in wheat, is regulated by the EU regulation in cereals and cereal-derived products. Its presence can be detected by chromatographic or rapid methods; the latter technique is generally used in control analysis, fulfilling the needs of the stakeholders of the wheat grain chain. Lateral flow strips are often used for the rapid detection of different mycotoxins in several agricultural products; regarding DON determination, different lateral flow immunochromatography strips are currently available, also providing quantitative results. The purpose of this work was to evaluate the accuracy of an innovative lateral flow device coupled to a bench top device, following a digital approach. The proposed method was compared to an LC-MS/MS method, analyzing 50 naturally contaminated wheat samples. The results obtained using the two methods were very similar and, applying a paired t-test, the mean difference between measurements resulted not significantly different (α = 0.003). The correlation between the results showed a slope of the line close to 1 (m = 0.9904) and a regression coefficient (r) of 0.9968. Full article
(This article belongs to the Special Issue Analytical Novelties and Challenges for the Detection of Natural Toxins)
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12 pages, 269 KiB  
Review
Review: Botulinum Toxin for Treatment of Focal Limb Dystonia
by Emma H. Kaplan, Michele Vecchio and David M. Simpson
Toxins 2025, 17(3), 122; https://doi.org/10.3390/toxins17030122 - 4 Mar 2025
Viewed by 888
Abstract
Focal limb dystonias (FLDs) are abnormal postures and muscle contractions in an arm or leg that can occur in the setting of specific activities or without any stimulus. This pathology can have a profound impact on quality of life and potentially limit work [...] Read more.
Focal limb dystonias (FLDs) are abnormal postures and muscle contractions in an arm or leg that can occur in the setting of specific activities or without any stimulus. This pathology can have a profound impact on quality of life and potentially limit work in those whose dystonias are brought on by activities related to their occupations. Botulinum toxin (BoNT) is approved for use in the United States by the Food and Drug Administration for several indications, including cervical dystonia and blepharospasm, but not for FLD. Despite this limitation, BoNT is frequently used clinically for FLD, generally with individualized dosing based on patient need and clinician expertise. Various methods exist for targeting treatment to the specific affected muscles and assessing the benefit of treatment. Small clinical trials have demonstrated the efficacy of BoNT, but larger controlled studies are needed. Full article
(This article belongs to the Special Issue Botulinum Toxins Injections for Hypertonic Limbs—Is It So Effective?)
18 pages, 7929 KiB  
Case Report
The Relationship Between Stiff Knee Gait Runner’s Dystonia and Musculoskeletal Knee Pathology: A Case Series
by Jared A. Stowers, Derek S. Day, Steven Jow, Sarah Heins, Euan Forrest, Yonathan M. Assefa, Paige M. Lind, Afreen Mushtaheed, Frances T. Sheehan and Katharine E. Alter
Toxins 2025, 17(3), 121; https://doi.org/10.3390/toxins17030121 - 3 Mar 2025
Viewed by 944
Abstract
Background: Runner’s dystonia (RD), a rare task-specific lower-limb dystonia affecting high-mileage runners, presents as abnormal lower-extremity muscle contractions during running. Treatment of RD is challenging and often confounded by significant diagnostic delays due to overlapping symptomatology with other conditions. This case series examines [...] Read more.
Background: Runner’s dystonia (RD), a rare task-specific lower-limb dystonia affecting high-mileage runners, presents as abnormal lower-extremity muscle contractions during running. Treatment of RD is challenging and often confounded by significant diagnostic delays due to overlapping symptomatology with other conditions. This case series examines the relationship between stiff knee gait RD and musculoskeletal (MSK) knee pathology. Methods: Eight RD cases, evaluated at the NIH Movement Disorders Clinic since 2018, were retrospectively reviewed. Patients underwent neurological, biomechanical, and MSK evaluations, including 3D motion analysis, surface electromyography, and knee ultrasound. Therapeutic interventions, including botulinum neurotoxin (BoNT) injections, were assessed. Results: Seven patients demonstrated stiff knee gait subtypes, with all having ipsilateral and/or contralateral knee effusions or tendinopathies. Three patients who received MSK interventions (e.g., aspiration, corticosteroid injections) combined with BoNT therapy experienced significant symptom improvement. One patient with isolated foot dystonia displayed different biomechanical patterns without knee pathology. Conclusions: RD patients with stiff knee gait often exhibit knee pathology, most likely due to altered biomechanics and running history. Addressing both issues is essential for optimizing treatment outcomes, reducing pain, and improving function, especially since pain can trigger dystonia. Future research should determine the ideal sequence of interventions for RD patients with MSK issues to develop effective, personalized treatment algorithms. Full article
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Article
An Unusual Outbreak of Ochratoxicosis Associated with Trigonella foenum-graecum Ingestion in Ruminants from Different Farms of Sicily
by Maria Rizzo, Patrizia Licata, Pietro Paolo Niutta, Michela Pugliese, Vito Macaluso, Giovanna Lucrezia Costa, Giuseppe Bruschetta and Fabio Bruno
Toxins 2025, 17(3), 120; https://doi.org/10.3390/toxins17030120 - 2 Mar 2025
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Abstract
Trigonella foenum-graecum is a widely cultivated legume in Mediterranean regions, and it is used for human and animal consumption, as well as for medical purposes. High temperatures and abundant rainfall during the spring season in Sicily favor the formation of an environment suitable [...] Read more.
Trigonella foenum-graecum is a widely cultivated legume in Mediterranean regions, and it is used for human and animal consumption, as well as for medical purposes. High temperatures and abundant rainfall during the spring season in Sicily favor the formation of an environment suitable for the growth and proliferation of fungi with the production of mycotoxins. In this study, ochratoxin A, aflatoxin, deoxynivalenol, zearalenone, fumonisin, and T-2 toxin concentrations in Trigonella foenum-graecum were determined in feed administered to ruminants and also in blood samples from cattle and sheep in order to evaluate the toxicity correlated to the possible presence of these mycotoxins based on the clinical signs observed in the animals. Analyses of mycotoxins in fenugreek and blood samples were conducted using the enzyme immunoassay KIT. Five extensive farms sited in the northwest of the Sicily region, with a total of 90 intoxicated animals, reported a concomitant unusual outbreak of neurological disorders. Decreased spinal reflex responses, postural abnormalities associated with weakness or recumbency, and hyperesthesia of the limbs suggested a problem regarding the peripheral nervous system. The mortality rate recorded was very high, even reaching 100% of the intoxicated animals. OTA intoxication in Sicilian ruminants represents an important warning on the vulnerability of farms to mycotoxin contamination and underlines the importance of preventive measures and monitoring in animal health management. Full article
(This article belongs to the Section Mycotoxins)
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