Toxins

31 pages, 1928 KB

Open AccessArticle

A General Food Chain Model for Bioaccumulation of Ciguatoxin into Herbivorous Fish in the Pacific Ocean Suggests Few Gambierdiscus Species Can Produce Poisonous Herbivores, and Even Fewer Can Produce Poisonous Higher Trophic Level Fish

by Michael J. Holmes and Richard J. Lewis

Toxins 2025, 17(11), 526; https://doi.org/10.3390/toxins17110526 (registering DOI) - 25 Oct 2025

Abstract

We adapt previous conceptual and numerical models of ciguateric food chains for the bioaccumulation of Pacific-ciguatoxin-1 (P-CTX-1) to a general model for bioaccumulation of P-CTX3C by parrotfish (Scarus frenatus, S. niger, and S. psittacus) that feed by scraping turf [...] Read more.

We adapt previous conceptual and numerical models of ciguateric food chains for the bioaccumulation of Pacific-ciguatoxin-1 (P-CTX-1) to a general model for bioaccumulation of P-CTX3C by parrotfish (Scarus frenatus, S. niger, and S. psittacus) that feed by scraping turf algae, and surgeonfish (Naso unicornis) that mostly feed on macroalgae. We also include the Indian Ocean parrotfish Chlorurus sordidus as a model for an excavator feeding parrotfish and include comparisons with the detritivorous surgeonfish Ctenochaetus striatus that brush-feeds on turf algae. Our food chain model suggests that, of the Gambierdiscus and Fukuyoa species so far analysed for ciguatoxin (CTX) production from the Pacific, only G. polynesiensis produces sufficient P-CTX3C to consistently produce parrotfish or N. unicornis with poisonous flesh. Our model suggests that insufficient CTX would accumulate into the flesh of parrotfish or N. unicornis to become poisonous from ingesting benthic dinoflagellates producing ≤0.03 pg P-CTX3C eq./cell, except from extended feeding times on high-density blooms and in the absence of significant depuration of CTX. Apart from G. polynesiensis, only G. belizeanus and possibly G. silvae and G. australes are thought to produce >0.03 pg P-CTX3C eq./cell in the Pacific. However, with relatively low maximum concentrations of ≤0.1 pg P-CTX3C eq./cell it is likely that their contribution is minimal. Our model also suggests that the differences between the area of turf algae grazed by parrotfish and similar sized C. striatus results in greater accumulation of CTX by this surgeonfish. This makes C. striatus a higher ciguatera risk than similar sized parrotfish, either directly for human consumption or as prey for higher trophic level fishes, consistent with poisoning data from Polynesia. It also suggests the possibility that C. striatus could bioaccumulate sufficient CTX to become mildly poisonous from feeding on lower toxicity Gambierdiscus or Fukuyoa species known to produce ≥0.02 P-CTX3C eq./cell. This indicates the potential for at least two food chain pathways to produce ciguateric herbivorous fishes, depending on the CTX concentrations produced by resident Gambierdiscus or Fukuyoa on a reef and the grazing capacity of herbivorous fish. However, only G. polynesiensis appears to produce sufficient P-CTX3C to consistently accumulate in food chains to produce higher trophic level fishes that cause ciguatera in the Pacific. We incorporate CTX depuration into our model to explore scenarios where mildly poisonous parrotfish or N. unicornis ingest CTX at a rate that is balanced by depuration to estimate the Gambierdiscus/Fukuyoa densities and CTX concentrations required for these fish to remain poisonous on a reef. Full article

(This article belongs to the Collection Ciguatoxin)

15 pages, 534 KB

Open AccessArticle

Leptin and Adiponectin as Uremic Adipokines: Associations with Survival in a Prospective Hemodialysis Cohort

by Thuy-Anh V. Bui, Amy S. You, Sara S. Kalantar, Jihoon Yoon, Yoko Narasaki, John Sy, Ramy Hanna, Andrea Daza, Yalitzi Guerrero, Anyssa Dang, Ria Arora, Danh V. Nguyen, Kamyar Kalantar-Zadeh and Connie M. Rhee

Toxins 2025, 17(11), 525; https://doi.org/10.3390/toxins17110525 (registering DOI) - 25 Oct 2025

Abstract

Background: While experimental models show that leptin and adiponectin have inverse effects on the cardiovascular system, it has been suggested that the leptin-to-adiponectin (L/A) ratio may be an important predictor of cardiovascular disease and death. Higher circulating leptin and adiponectin levels are observed [...] Read more.

Background: While experimental models show that leptin and adiponectin have inverse effects on the cardiovascular system, it has been suggested that the leptin-to-adiponectin (L/A) ratio may be an important predictor of cardiovascular disease and death. Higher circulating leptin and adiponectin levels are observed in uremia due to decreased renal degradation and/or clearance and increased production. We sought to examine the association between the L/A ratio and mortality in a prospective hemodialysis cohort. Methods: Among a prospective cohort of 448 hemodialysis patients from the NIH “Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease (CKD) (MADRAD) study who underwent leptin and adiponectin measurements, we examined characteristics associated with high leptin and adiponectin (defined as the highest tertile) using logistic regression. We then examined the association of L/A ratio levels (categorized as tertiles) with all-cause mortality using Cox regression. Results: Multivariable logistic regression analyses showed female sex, diabetes, presence of an arteriovenous fistula/graft, and lower serum albumin, IL-6, and adiponectin were associated with high leptin, whereas female sex, longer vintage, Black race, higher IL-6, and lower leptin were associated with high adiponectin. When examining L/A ratios, the highest tertile was associated with lower mortality in case-mix Cox models (ref: lowest tertile): HR (95% CI) 0.14 (0.06–0.35). These associations were robust in analyses that additionally adjusted for laboratory covariates: (HR 95% CI) 0.18 (0.07–0.46). Conclusions: In a prospective cohort of hemodialysis patients, inflammation and malnutrition markers were associated with lower leptin and higher adiponectin levels. Additionally, high L/A ratio levels were associated with lower mortality. Further studies are needed to determine the mechanisms relating adipocytokines, inflammation and nutrition, and survival in this population. Full article

(This article belongs to the Special Issue Contemporary and Emerging Modalities of Kidney Assistance Therapy for Patients with Kidney Dysfunction Requiring Dialysis)

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18 pages, 553 KB

Open AccessArticle

AI and Biotechnology to Combat Aflatoxins: Future Directions for Modern Technologies in Reducing Aflatoxin Risk

by Charitha J. Gamlath and Felicia Wu

Toxins 2025, 17(11), 524; https://doi.org/10.3390/toxins17110524 - 23 Oct 2025

Abstract

Although a decades-old problem in food safety, aflatoxin has largely resisted human control methods. This situation could be mitigated using new technologies that could provide better control all along the food supply chain, for crops frequently infected with the causative fungi Aspergillus flavus [...] Read more.

Although a decades-old problem in food safety, aflatoxin has largely resisted human control methods. This situation could be mitigated using new technologies that could provide better control all along the food supply chain, for crops frequently infected with the causative fungi Aspergillus flavus and A. parasiticus, which produce aflatoxin. Generative artificial intelligence (AI) and modern biotechnology could offer, and have offered, a suite of potential solutions to reducing both fungal infection and aflatoxin contamination of foods. In this paper, we describe these technologies, as well as means by which they may be utilized to reduce aflatoxin risk along the food supply chain. We discuss how regulatory frameworks worldwide may be restrictive for biotechnologies in certain parts of the world, but are relatively less stringent for AI at present. To the extent that these technologies can be harnessed and deployed safely to combat the problem of aflatoxins, we encourage research and development in these areas to improve the precision, accuracy, and speed by which to deal with this food safety risk. 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, 8136 KB

Open AccessArticle

Snake Venom C-Type Lectin-like Protein Vaa-Snaclec-3/2 Efficiently Prevents Carotid Artery Thrombosis in a Mouse Model Without Compromising Blood Coagulation

by Monika C. Žužek, Igor Križaj, Miran Brvar, Tomaž Trobec, Simona Kranjc Brezar, Mojca Dobaja Borak, Adrijana Leonardi, Kity Požek, Milka Vrecl and Robert Frangež

Toxins 2025, 17(11), 523; https://doi.org/10.3390/toxins17110523 - 23 Oct 2025

Abstract

Platelets play pivotal roles in thromboembolic diseases, such as myocardial infarction and ischemic stroke. In patients envenomed by the snake Vipera a. ammodytes (Vaa), pronounced and transient thrombocytopenia without bleeding is observed. We previously showed that Vaa-snaclec-3/2, the snake venom [...] Read more.

Platelets play pivotal roles in thromboembolic diseases, such as myocardial infarction and ischemic stroke. In patients envenomed by the snake Vipera a. ammodytes (Vaa), pronounced and transient thrombocytopenia without bleeding is observed. We previously showed that Vaa-snaclec-3/2, the snake venom C-type lectin-like protein, mediates this effect ex vivo. Here, we extended our study of the antithrombotic potential of this protein in vivo using a mouse model of ferric chloride (FeCl₃)-induced carotid artery thrombosis. Prior to inducing thrombus formation, the mice received 1, 5, 10, 20, or 50 μg/kg Vaa-snaclec-3/2 intravenously. Afterward, the arterial blood flow was monitored with a perivascular Doppler probe. Additionally, the platelet count in the peripheral venous blood; tail bleeding time; and liver, lung, kidney, spleen, and heart histology were evaluated. The lowest dose of Vaa-snaclec-3/2 that we showed to cause severe thrombocytopenia and completely inhibit FeCl₃-induced thrombus formation was 20 µg/kg. This dose prolonged the median tail bleeding time from 86.5 to 153.5 s but did not induce acute spontaneous hemorrhage, as demonstrated by histological analysis. Histology revealed no signs of apoptosis, necrosis or other degenerative changes in the inspected organs of mice exposed to 20 μg/kg Vaa-snaclec-3/2. Platelet clusters were observed only in the lungs, which appear to be the primary site of platelet sequestration and the cause of thrombocytopenia. Taken together, our findings highlight the high potential of Vaa-snaclec-3/2 as a safe and effective antithrombotic agent for the transient prevention of thrombosis in acute clinical settings. Full article

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

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4 pages, 194 KB

Open AccessEditorial

The Future of Bt Proteins: From Pore Formation and Insect Resistance to the Next Generation of Pest Control

by Mario Soberón and Alejandra Bravo

Toxins 2025, 17(11), 522; https://doi.org/10.3390/toxins17110522 - 23 Oct 2025

Abstract

The remarkable success of Bacillus thuringiensis [Bt] in pest control worldwide resides not only on the extraordinary potency of its pesticidal proteins, but also on their narrow insect specificity, their safety for humans, and biodegradability [...] Full article

(This article belongs to the Section Bacterial Toxins)

9 pages, 1002 KB

Open AccessBrief Report

Effect of Expanded Hemodialysis with the Theranova Dialyzer on the Platelet-to-Lymphocyte Ratio and Inflammatory Markers

by You Hyun Jeon, Hee-Yeon Jung, Ji-Young Choi, Sun-Hee Park, Chan-Duck Kim, Yong-Lim Kim, Jeong-Hoon Lim and Jang-Hee Cho

Toxins 2025, 17(11), 521; https://doi.org/10.3390/toxins17110521 - 22 Oct 2025

Abstract

The platelet-to-lymphocyte ratio (PLR) has been used as a marker of inflammation, endothelial damage, and a predictor of mortality. Expanded hemodialysis (HDx) using medium cut-off dialyzer (MCO) can effectively clear medium-sized uremic toxins. This study evaluated the effect of the Theranova dialyzer, a [...] Read more.

The platelet-to-lymphocyte ratio (PLR) has been used as a marker of inflammation, endothelial damage, and a predictor of mortality. Expanded hemodialysis (HDx) using medium cut-off dialyzer (MCO) can effectively clear medium-sized uremic toxins. This study evaluated the effect of the Theranova dialyzer, a type of MCO dialyzer, on PLR and uremia-related inflammatory markers. A total of 44 patients with maintenance hemodialysis (HD) using high-flux dialyzer were randomly allocated to the Theranova or high-flux group. PLR and inflammatory markers including fibroblast growth factor 23, tumor necrosis factor-α (TNF-α), and interleukin 6 were evaluated every 4 weeks. The changes in PLR and the reduction ratio of inflammatory markers were compared between two groups during the 12-week study period. The baseline characteristics and PLR were not different between groups. After 12 weeks, the levels of PLR, and TNF-α were significantly lower in the Theranova group compared to the high-flux group (all p < 0.05). The generalized estimating equation model also revealed a significant decrease in PLR over time in the Theranova group than in the high-flux group (p = 0.04). The fold change in 12-week PLR to baseline PLR was lower in the Theranova group than in the high-flux group (p = 0.03). In the multivariable linear regression analysis, the Theranova dialyzer showed a negative correlation with the PLR fold change (β = −0.32, p = 0.04). Our results showed that HDx using the Theranova dialyzer improves PLR over time compared to the high-flux HD. The superior removal of the inflammatory uremic toxins by the Theranova dialyzer may have reduced inflammation and inflammation-related complications in HD patients. Full article

(This article belongs to the Special Issue New Insights in Uremic Toxins and Toxin-Related Outcomes in Chronic Kidney Disease)

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19 pages, 4765 KB

Open AccessArticle

How Sodium and Calcium Ions Pass Through Batrachotoxin-Bound Sodium Channel

by Boris S. Zhorov

Toxins 2025, 17(10), 520; https://doi.org/10.3390/toxins17100520 - 21 Oct 2025

Abstract

Steroidal sodium channel agonist batrachotoxin (BTX), one of the most potent animal toxins, dramatically increases calcium permeation and alters other channel characteristics. In a cryoEM structure of rat sodium channel Nav1.5 with two BTX-B molecules, one toxin binds between repeats III and IV [...] Read more.

Steroidal sodium channel agonist batrachotoxin (BTX), one of the most potent animal toxins, dramatically increases calcium permeation and alters other channel characteristics. In a cryoEM structure of rat sodium channel Nav1.5 with two BTX-B molecules, one toxin binds between repeats III and IV and exposes to the pore lumen two oxygen atoms and protonatable nitrogen. The mechanism of ion permeation and selectivity in BTX-bound channel is unclear. Here Monte Carlo energy-minimized profiles of sodium and calcium ions pulled through the pore were computed in models with various protonated states of the DEKA lysine and BTX-B. The only model where the ions readily passed by the DEKA lysine and BTX-B involved their deprotonated nitrogens. In this model, electronegative atoms of BTX-B attracted a permeant cation that stabilized the “dunked” lysine through electrostatic interactions and nearby water molecules. This would retard reprotonation of the lysine and its “uplifting” to the DEKA carboxylates, which otherwise attracts calcium. The results suggest how sodium and calcium ions pass through BTX-bound sodium channel and why BTX increases calcium permeation. The study supports an earlier hypothesis that during the sodium ion permeation cycle, the DEKA lysine alternates between uplifted and dunked conformations in the protonated and deprotonated states, respectively, while the sodium-displaced proton and the sodium ion nullify the net electrical charge at the DEKA region. Full article

(This article belongs to the Section Animal Venoms)

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15 pages, 1136 KB

Open AccessArticle

The Effective Way of Botulinum Toxin Injection to Reduce Bite Force: Preliminary Study

by Kun-Hwa Kang, Jae-Kwang Jung, Jin-Seok Byun and Ji Rak Kim

Toxins 2025, 17(10), 519; https://doi.org/10.3390/toxins17100519 - 21 Oct 2025

Abstract

This study investigated bite force changes after botulinum toxin type A (BoNT-A) injection into different masticatory muscles. Thirty-five male participants were divided into three groups: masseter only (M), masseter and temporalis (MT), and masseter, temporalis, and medial pterygoid (MTP). Bite force was measured [...] Read more.

This study investigated bite force changes after botulinum toxin type A (BoNT-A) injection into different masticatory muscles. Thirty-five male participants were divided into three groups: masseter only (M), masseter and temporalis (MT), and masseter, temporalis, and medial pterygoid (MTP). Bite force was measured before and up to 6 months after injection with the Dental Prescale II system. Baseline values showed no significant group differences. Group M exhibited significant reduction at 1 and 2 weeks, with recovery within 1 month. Group MT showed a similar transient decrease, also recovering after 1 month. In contrast, Group MTP demonstrated a more pronounced and prolonged reduction, persisting up to 4 months before recovery. These results indicate that the extent and duration of BoNT-A effects depend on the number of muscles injected. Multi-muscle injections, including the medial pterygoid, provide more durable suppression. However, further research involving patient populations is needed to clarify whether multi-muscle injection strategies provide therapeutic benefits in clinical conditions such as temporomandibular disorders or oromandibular dystonia. Full article

(This article belongs to the Special Issue Application of Botulinum Toxin in Facial Diseases)

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18 pages, 795 KB

Open AccessArticle

Assessment of Maternal Exposure to Mycotoxins During Pregnancy Through Biomarkers in Fetal and Neonatal Tissues

by João Thiago Aragão Fermiano, Sher Ali, Sana Ullah, Vanessa Theodoro Rezende, Roice Eliana Rosim, Fernando Gustavo Tonin, Walusa Assad Gonçalves Ferri, Alessandra Cristina Marcolin, Leandra Naira Zambelli Ramalho, Carlos Augusto Fernandes de Oliveira and Fernando Silva Ramalho

Toxins 2025, 17(10), 518; https://doi.org/10.3390/toxins17100518 - 21 Oct 2025

Abstract

This study aimed to conduct a first evaluation of maternal exposure to mycotoxins during pregnancy in Brazil through quantification of biomarkers in liver and serum samples from stillborn and neonates autopsied in the Clinical Hospital of Ribeirão Preto, state of São Paulo. Liver [...] Read more.

This study aimed to conduct a first evaluation of maternal exposure to mycotoxins during pregnancy in Brazil through quantification of biomarkers in liver and serum samples from stillborn and neonates autopsied in the Clinical Hospital of Ribeirão Preto, state of São Paulo. Liver tissue (n = 43) and serum (n = 38) samples were collected from 43 patients and analyzed for biomarkers of aflatoxins (AFs), ochratoxin A (OTA), fumonisins (FBs), zearalenone (ZEN), deoxynivalenol (DON), T-2 and HT-2 toxins by ultra-performance liquid chromatography coupled to tandem mass spectrometry. In total, 9 samples of liver (20.9%) and 33 serum (86.8%) had quantifiable levels of mycotoxins. In liver samples, aflatoxin M₁ (AFM₁) was quantified in two samples (median level: 0.38 ng/g), while four samples had OTA residues (median: 0.31 ng/g) and one contained ZEN (3.6 ng/g). Compared with liver tissue, serum samples had higher occurrence rates of mycotoxins, particularly AFM₁, OTA and ZEN. Nineteen serum samples (50%) contained 2–4 types of mycotoxins, indicating an effective transplacental transfer of major mycotoxins during pregnancy. Median levels of AFM₁, OTA, FB₁, ZEN, DON, T-2 and HT-2 toxins in serum samples were 0.48, 3.39, 30.6, 10.53, 5.71, 2.85 and 10.84 ng/mL, respectively. The most frequent cause of death was extreme prematurity (33% of cases), followed by preterm premature rupture of membranes (16% of cases) and morphological abnormalities (42% of cases). Results of this trial suggest potential associations between dietary mycotoxins and congenital anomalies. Further research should clarify the transplacental transfer of mycotoxins and their association with toxic effects during human prenatal development. 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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4 pages, 589 KB

Open AccessObituary

Thomas W. Kensler (1948–2025): A Legend in Antioxidant Response Pathways and Aflatoxin Carcinogenesis Research

by David L. Eaton and John D. Groopman

Toxins 2025, 17(10), 517; https://doi.org/10.3390/toxins17100517 - 21 Oct 2025

Abstract

It is with great sadness that we must include in this Special Volume of Toxins a memorial to our close friend and colleague [...] 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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18 pages, 3033 KB

Open AccessArticle

Self-Sufficient Aflatoxin Decontamination System: MOF-Based Composite Membrane with Peroxidase-Mimic and Controlled H₂O₂ Generation

by Xiaofei Cheng, Wenzhong Zhu, Xueting Zhu, Jinmin Zhang, Jia Yang, Huali Wang, Xiaoqin Mo, Chi Zhang and Lina Wu

Toxins 2025, 17(10), 516; https://doi.org/10.3390/toxins17100516 - 20 Oct 2025

Abstract

Aflatoxin B1 (AFB1) and its metabolite aflatoxin M1 (AFM1) are stable and carcinogenic mycotoxins that are commonly found in dairy products, posing serious food safety concerns. However, conventional degradation methods face limited degradation efficiency and high energy demand. Here, we develop an innovative [...] Read more.

Aflatoxin B1 (AFB1) and its metabolite aflatoxin M1 (AFM1) are stable and carcinogenic mycotoxins that are commonly found in dairy products, posing serious food safety concerns. However, conventional degradation methods face limited degradation efficiency and high energy demand. Here, we develop an innovative polyvinylidene fluoride (PVDF) composite membrane incorporating Fe/Co-based metal-organic frameworks (MOF) (Named Fe/Co-MIL-88B(NH₂)) and CaO₂ for targeted aflatoxin removal from milk. This system integrates two synergistic mechanisms: (1) hierarchical porous MOF structures enabling superior aflatoxin adsorption capacity and peroxidase-like catalytic activity, and (2) CaO₂ acts as a controllable-release H₂O₂ donor, supplying a steady flux of reactive oxygen species without the addition of exogenous H₂O₂. Moreover, the PVDF membrane with mechanical stability offers uniform immobilization of active components, which prevents the aggregation of nanozymes. As a result, the integrated membrane achieves high degradation efficiency for AFB1 and AFM1, exceeding 95% within 60 min. By eliminating external oxidant addition and minimizing collateral nutrient damage, the technology demonstrates remarkable operational stability (>10 cycles) and milk quality preservation capability. This breakthrough establishes an efficient and reusable detoxification method, providing new opportunities for mycotoxin mitigation in dairy products through spatiotemporal control of reactive oxygen species. Full article

(This article belongs to the Special Issue Detection, Biosynthesis and Control of Mycotoxins (4th Edition))

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24 pages, 2023 KB

Open AccessReview

New Insights into Mycotoxin Contamination, Detection, and Mitigation in Food and Feed Systems

by Marija Kovač Tomas and Iva Jurčević Šangut

Toxins 2025, 17(10), 515; https://doi.org/10.3390/toxins17100515 - 20 Oct 2025

Abstract

Mycotoxins are ubiquitous and unavoidable contaminants in food and feed, posing significant health risks through toxicity syndromes collectively referred to as mycotoxicoses. With climate change enhancing the conditions favorable for fungal growth and mycotoxin production, concerns over food and feed safety are increasingly [...] Read more.

Mycotoxins are ubiquitous and unavoidable contaminants in food and feed, posing significant health risks through toxicity syndromes collectively referred to as mycotoxicoses. With climate change enhancing the conditions favorable for fungal growth and mycotoxin production, concerns over food and feed safety are increasingly pressing. Although regulatory frameworks have been established to monitor and limit the exposure, effective mitigation remains a challenge. This paper provides a comprehensive overview of recent advances in the prevention, detection, and control of mycotoxins, with particular emphasis on innovative strategies such as plant-derived bioactives, nanotechnology-based systems, genetic engineering approaches, antibody-mediated technology, and emerging non-thermal processing methods. Full article

(This article belongs to the Special Issue Strategies for Mitigating Mycotoxin Contamination in Food and Feed)

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22 pages, 4076 KB

Open AccessArticle

Protective Effect of Ethoxyquin and N-acetylcysteine on Biochemical and Pathological Changes Induced by Chronic Exposure to Aflatoxins in Laying Hens

by María Carolina de-Luna-López, Arturo Gerardo Valdivia-Flores, Teódulo Quezada-Tristán, Raúl Ortiz-Martínez, Erika Janet Rangel-Muñoz, Emmanuel Hernández-Valdivia, Esther Albarrán-Rodríguez and Elizabeth de Santiago-Díaz

Toxins 2025, 17(10), 514; https://doi.org/10.3390/toxins17100514 - 20 Oct 2025

Abstract

Aflatoxins (AFs) represent a major threat to poultry health and food safety due to their hepatotoxic, immunosuppressive, and carcinogenic effects. This study evaluated the chemoprotective potential of ethoxyquin (EQ) and N-acetylcysteine (NAC) in laying hens (80.8 and 33.3 mg/kg BW/d) exposed to chronic [...] Read more.

Aflatoxins (AFs) represent a major threat to poultry health and food safety due to their hepatotoxic, immunosuppressive, and carcinogenic effects. This study evaluated the chemoprotective potential of ethoxyquin (EQ) and N-acetylcysteine (NAC) in laying hens (80.8 and 33.3 mg/kg BW/d) exposed to chronic dietary AFs contamination (0.0–1.5 mg/kg). A total of 360 Hy-Line W36 Leghorn hens were monitored over 72 weeks using biochemical and histopathological analyses of liver and kidney tissues. NAC significantly (p < 0.01) increased hepatic and renal levels of reduced glutathione (GSH) and stimulated glutathione S-transferases (GST) and gamma-glutamyl transferase (GGT) activity, enhancing detoxification. Both agents significantly (p < 0.05) reduced plasma ALT and AST levels, preserved total protein concentrations, and attenuated liver and kidney hypertrophy. EQ demonstrated antioxidant effects, stabilizing enzymatic responses and limiting tissue damage. Histopathological analysis revealed fewer structural alterations and cellular degeneration, especially in the NAC-treated group (p < 0.01). These results suggest that NAC and EQ activate endogenous detoxification mechanisms, both enzymatic and non-enzymatic, effectively mitigating chronic aflatoxin toxicity. Their dietary supplementation offers a safe and sustainable chemoprotection strategy to support poultry health and productivity, particularly in regions facing high mycotoxin exposure. Full article

(This article belongs to the Special Issue Aflatoxins: Contamination, Analysis and Control)

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29 pages, 982 KB

Open AccessReview

The Ambivalent Nature of Bacteroides fragilis and the Interaction with Clostridioides difficile: Benefits and Disadvantages for the Human Host

by Patrizia Spigaglia

Toxins 2025, 17(10), 513; https://doi.org/10.3390/toxins17100513 - 19 Oct 2025

Abstract

Bacteroides fragilis is a usually beneficial colonizer of the human gut that can also act as an opportunistic pathogen, causing infection and contributing to the development and progression of important diseases. The production and secretion of the B. fragilis toxin (BFT), the main [...] Read more.

Bacteroides fragilis is a usually beneficial colonizer of the human gut that can also act as an opportunistic pathogen, causing infection and contributing to the development and progression of important diseases. The production and secretion of the B. fragilis toxin (BFT), the main virulence factor of this bacterium, distinguishes enterotoxigenic (ETBF) from non-toxigenic (NTBF) strains. Although NTBF does not produce the BFT, certain strains can exhibit unexpected pathogenic characteristics. The complex interactions between B. fragilis and the other intestinal bacteria, such as Clostridioides difficile, the leading cause of antibiotic-associated diarrhea in healthcare settings, highlights its ambivalent role of benefactor and pathogen. In fact, although B. fragilis plays a part in preventing colonization and infection due to C. difficile (CDI), both these anaerobic bacteria can contribute to the development and progression of colorectal cancer (CRC), one of the most prevalent malignant tumors of the digestive tract. This review provides an overview of the dual nature of B. fragilis, focusing on the peculiarities of ETBF and NTBF, delving into B. fragilis interaction with C. difficile and impacts on the host. Full article

(This article belongs to the Special Issue Enterotoxigenic Bacteroides fragilis Toxin: Biological Properties and Pathogenesis)

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15 pages, 1219 KB

Open AccessArticle

Mechanisms of Cellular Responses of the Natural Alkaloid Caulerpin and Its Similarities with the Lipid-Lowering Agent Fenofibrate in Mytilus galloprovincialis

by Michela Panni, Marica Mezzelani, Maria Elisa Giuliani, Paola Nisi Cerioni, Alessandro Nardi, Ernesto Mollo, Francesco Regoli, Maura Benedetti and Stefania Gorbi

Toxins 2025, 17(10), 512; https://doi.org/10.3390/toxins17100512 - 18 Oct 2025

Abstract

Marine-derived natural products have attracted increasing attention due to their promising pharmacological potential against various diseases. The present study investigated the hypolipidemic properties of the alkaloid caulerpin, a secondary metabolite of green algae of the genus Caulerpa, through an ex vivo approach [...] Read more.

Marine-derived natural products have attracted increasing attention due to their promising pharmacological potential against various diseases. The present study investigated the hypolipidemic properties of the alkaloid caulerpin, a secondary metabolite of green algae of the genus Caulerpa, through an ex vivo approach with Precision-Cut Tissue Slices (PCTSs) of Mytilus galloprovincialis digestive glands. PCTSs were exposed to caulerpin (CAU) (100 µM) and fenofibrate (FFB) (100 µM) for 24, 48, and 72 h. Analyses of molecular and cellular responses pertaining to lipid metabolism suggested a similar mechanism of action between CAU and FFB in marine invertebrate species, resulting in a decrease in neutral lipid content ranging from 50 to 70%. CAU’s hypolipidemic action was not associated with increased prooxidant conditions, and slower metabolism of the natural alkaloid compared to FFB was indicated by the response of biotransformation and excretion pathways. Overall, these findings provide initial insights into the potential valorization of CAU for pharmaceutical and nutraceutical applications, highlighting the need for further investigation into its mechanisms of action, possible side effects, and interactions with other drugs. Full article

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20 pages, 7890 KB

Open AccessArticle

One Bloom Is Not Like the Other—Distinct Environmental Drivers Result in Domoic Acid Events in Monterey Bay, California

by Aubrey Trapp, Andrew Baker, Kendra Hayashi and Raphael M. Kudela

Toxins 2025, 17(10), 511; https://doi.org/10.3390/toxins17100511 - 17 Oct 2025

Abstract

Domoic acid (DA), produced by Pseudo-nitzschia diatoms, is the one of the major toxin threats from harmful algal blooms (HABs) on the west coast of the United States. DA events vary in magnitude, timing, and duration, and elucidating drivers for individual events is [...] Read more.

Domoic acid (DA), produced by Pseudo-nitzschia diatoms, is the one of the major toxin threats from harmful algal blooms (HABs) on the west coast of the United States. DA events vary in magnitude, timing, and duration, and elucidating drivers for individual events is a persistent challenge. Monterey Bay experiences near-annual DA events and hosts long-term HAB monitoring at the Santa Cruz Municipal Wharf (SCW). Here we characterize two toxin events, occurring in May 2023 and March 2024. The events were similar in magnitude and duration, but an exploration of physical, biological, and chemical dynamics revealed distinct environmental drivers. These differences resulted in a significant deviation in cellular DA (cDA) within the same species of Pseudo-nitzschia. In addition, opportunistic solid-phase adsorption toxin tracking (SPATT) was used for environmental metabolomics. The novel application of SPATT revealed 159 metabolites that were strongly correlated with DA in both events and produced a spectral match to a new marine natural product using Global Natural Products Social Molecular Networking (GNPS). This work takes a multivariable approach to understanding toxin drivers and lends proof of concept for the integration of environmental metabolomics in HAB monitoring. Full article

(This article belongs to the Special Issue Ecology and Evolution of Harmful Algal Blooms)

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13 pages, 1200 KB

Open AccessArticle

Development of Lab-on-a-Chip LAMP and Real-Time PCR Assays to Detect Aflatoxigenic Aspergillus flavus and Aspergillus parasiticus in Hazelnuts

by Slavica Matić, Livio Cognolato, Martina Sanna, Monica Mezzalama, Riccardo Laurenti and Davide Spadaro

Toxins 2025, 17(10), 510; https://doi.org/10.3390/toxins17100510 - 17 Oct 2025

Abstract

Aflatoxins, which are potentially genotoxic and carcinogenic substances, are mainly produced by the Aspergillus section Flavi, including Aspergillus flavus and A. parasiticus. Current Aspergillus spp. detection is often based on molecular methods, such as real-time PCR and loop-mediated isothermal amplification (LAMP), [...] Read more.

Aflatoxins, which are potentially genotoxic and carcinogenic substances, are mainly produced by the Aspergillus section Flavi, including Aspergillus flavus and A. parasiticus. Current Aspergillus spp. detection is often based on molecular methods, such as real-time PCR and loop-mediated isothermal amplification (LAMP), targeting genes of the aflatoxin biosynthetic cluster. In this study, we developed a Lab-on-a-Chip (LoC) method based on real-time PCR and on LAMP for the specific detection of aflatoxigenic strains of A. flavus and A. parasiticus from infected hazelnuts. LoC-LAMP and LoC-real-time PCR assays were tested in terms of specificity, sensitivity, speed, and repeatability. The microfluidic chip allowed quick, specific, sensitive, simple, automatized, cheap, and user-friendly detection of aflatoxigenic strains of A. flavus and A. parasiticus. The LoC-LAMP showed a limit of detection (LOD) of 10 fg of DNA, while the LoC-real-time PCR showed a LOD of 10 pg of DNA. Achieving comparable sensitivity to that of LAMP and real-time PCR techniques, both LoC methods developed in this work offer the advantages of automation, minimal sample requirements, reagent requirements, and cost-effectiveness. Overall, the developed methods open the perspective for alternative monitoring of aflatoxigenic fungi in the agri-food industry. Full article

(This article belongs to the Section Mycotoxins)

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15 pages, 18289 KB

Open AccessArticle

Mapping Dural and Periosteal SV2C, a Botulinum Toxin A Receptor, in the Mouse

by Anisa Dehghani, Agustin Melo-Carrillo, Andrew M. Strassman, Ron S. Broide, Aubrey Manack Adams, Brett Dabruzzo, Mitchell F. Brin and Rami Burstein

Toxins 2025, 17(10), 509; https://doi.org/10.3390/toxins17100509 - 17 Oct 2025

Abstract

Objectives: There has been a long-standing debate over the presence or absence of receptors for botulinum toxin A (BoNT/A) in cephalic areas relevant to migraine pathophysiology and onabotulinumtoxinA (onabotA) sites of action in migraine prevention. To address this issue, we sought to investigate [...] Read more.

Objectives: There has been a long-standing debate over the presence or absence of receptors for botulinum toxin A (BoNT/A) in cephalic areas relevant to migraine pathophysiology and onabotulinumtoxinA (onabotA) sites of action in migraine prevention. To address this issue, we sought to investigate for the first time whether synaptic vesicle protein 2C (SV2C), one member of the SV2 receptor family, is present in axons innervating the dura and periosteum. Methods: Single- and double- labeling immunohistochemical techniques were used to map and characterize the distribution of axons containing SV2C, the third isoform of the SV2 glycoprotein, in the mouse dura and periosteum. Results: Dense networks of axons containing SV2C receptors were distributed throughout all regions of the dura and periosteum. In the dura, SV2C-LIR axons were found in 43% of all peripherin-LIR fibers, 49% of all CGRP-LIR fibers, and 75% of all NaV1.8-LIR fibers. In the periosteum, SV2C-LIR was found in 38% of all peripherin-LIR fibers, 53% of all CGRP-LIR fibers, and 68% of all NaV1.8-LIR fibers. Conclusions: We interpret these findings as suggesting that many of the labeled axons are peripheral nerve axons (peripherin-positive) of unmyelinated sensory and possibly parasympathetic origin (CGRP-positive), and that some of these sensory axons are nociceptors (NaV1.8-positive). Clinically, these findings demonstrate an abundance of axons containing onabotA receptors in the vicinity of scalp structures commonly injected with onabotA for the treatment of chronic migraine. Dense labeling in the periosteum provides another rationale for the possibility that onabotA injections in this layer of the scalp may be advantageous. Full article

(This article belongs to the Section Bacterial Toxins)

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24 pages, 3732 KB

Open AccessReview

The Elias University Hospital Approach: A Visual Guide to Ultrasound-Guided Botulinum Toxin Injection in Spasticity, Part IV—Distal Lower Limb Muscles

by Marius Nicolae Popescu, Claudiu Căpeț, Cristina Popescu and Mihai Berteanu

Toxins 2025, 17(10), 508; https://doi.org/10.3390/toxins17100508 - 16 Oct 2025

Abstract

Spasticity of the distal lower limb substantially impairs stance, gait, and quality of life in patients with upper motor neuron lesions. Although ultrasound-guided botulinum toxin A (BoNT-A) injections are increasingly employed, structured, muscle-specific visual guidance for the distal lower limb remains limited. This [...] Read more.

Spasticity of the distal lower limb substantially impairs stance, gait, and quality of life in patients with upper motor neuron lesions. Although ultrasound-guided botulinum toxin A (BoNT-A) injections are increasingly employed, structured, muscle-specific visual guidance for the distal lower limb remains limited. This study provides a comprehensive guide for ultrasound-guided BoNT-A injections across ten key distal lower limb muscles: gastrocnemius, soleus, tibialis posterior, flexor hallucis longus, flexor digitorum longus, tibialis anterior, extensor hallucis longus, flexor digitorum brevis, flexor hallucis brevis, and extensor digitorum longus. For each muscle, we present (1) Anatomical positioning relative to osseous landmarks; (2) Sonographic identification cues and dynamic features; (3) Zones of intramuscular neural arborization optimal for injection; (4) Practical injection protocols derived from literature and clinical experience. High-resolution ultrasound images and dynamic videos illustrate real-life muscle behavior and guide injection site selection. This guide facilitates precise targeting by correlating sonographic signs with optimal injection zones, addresses common spastic patterns—including equinus, varus, claw toe, and hallux deformities—and integrates fascial anatomy with motor-point mapping. This article completes the Elias University Hospital visual series, providing clinicians with a unified framework for effective spasticity management to improve gait, posture, and patient autonomy. Full article

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