Toxins最新文献

Anatoxin-a (ATX-a) is a cyanotoxin whose toxicological profile has been underinvestigated in comparison to other cyanotoxins such as microcystins (MCs) or cylindrospermopsin (CYN). However, its wide distribution, occurrence, and toxic episodes justify more attention. It is classified as a neurotoxin, but it has also been reported to affect other organs and systems. Thus, the aim of this study was to establish, as a first tier in its toxicological evaluation, its cytotoxicity in a wide range of cell lines representative of potential target organs (N2a, SH-SY5Y, HepG2, Caco2, L5178Y Tk^+/-, THP-1 and Jurkat). As limited effects were observed after exposure to up to 200 µg/mL of ATX-a for 24 h (only Jurkat and THP-1 cells showed reduced cell viability), cell uptake experiments were performed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The results showed that the immune system cells had the highest percentage of ATX-a in the intracellular fraction, followed by neuronal cells and finally Caco-2 and HepG2 cells. Moreover, the expression of genes related to cell death mechanisms in THP-1 cells was also analyzed by polymerase chain reaction (PCR) and showed no changes under the conditions tested. Further research is required on ATX-a's toxic effects and toxicokinetics to contribute to its risk assessment.

The frequency and intensity of harmful cyanobacterial blooms have increased in the last decades, posing a risk to public health since conventional water treatments do not effectively remove extracellular cyanotoxins. Consequently, advanced technologies such as the Fenton process are required to ensure water safety. The cyanotoxin cylindrospermopsin (CYN) demands special attention, as it is abundant in the extracellular fraction and has a high toxicological potential. Hence, this study aimed to assess the application of the Fenton process for the oxidation of CYN spiked in natural water from Paranoá Lake (Brasília, Brazil). The H₂O₂/Fe(II) molar ratio was evaluated from 0.2 to 3.4, with an optimum molar ratio of 0.4, achieving a CYN degradation efficiency of 97.8% when using 100 µM of H₂O₂ and 250 µM of Fe(II). The CYN degradation efficiency, using 75 µM of H₂O₂ and 187.5 µM of Fe(II), decreased by increasing the initial pH (from 96.2% at pH 2 to 23.0% at pH 9) and the initial CYN concentration (from 93.7% at 0.05 µM of CYN to 85.0% at 0.2 µM of CYN). At the optimum H₂O₂/Fe(II) molar ratio of 0.4, the hydroxy radical scavengers tested (124.3 µM C of algogenic organic matter, 5 mg L^-1 of humic acid, and 513.3 µM of methanol) did not considerably affect the CYN degradation, reaching a maximum CYN degradation reduction from 98.3% to 82.2%.

The increasing contamination of cereals by micromycetes and mycotoxins during malting still poses an unresolved food safety problem. This study characterises the potential of the novel, rapidly developing food production technology of Pulsed Electric Field (PEF) to reduce the viability of Fusarium fungi and the production of mycotoxins during malting. Barley, artificially inoculated with four Fusarium species, was treated by PEF with two different intensities and then malted using a standard Pilsner-type technology. Concentrations of fungi were quantified by RT-PCR, expression of fungal growth-related genes was assessed using mRNA sequencing, and mycotoxin levels were analysed by U-HPLC-HRMS/MS. Despite the different trends for micromycetes and mycotoxins after application of variously intense PEF conditions, significant reductions were generally observed. The greatest decrease was for F. sporotrichioides and F. poae, where up to six fold lower levels were achieved for malts produced from the PEF-treated barley when compared to the control. For F. culmorum and F. graminearum, up to a two-fold reduction in the PEF-generated malts was observed. These reductions mostly correlated with a decrease in relevant mycotoxins, specifically type A trichothecenes.

Food poisoning outbreaks frequently involve staphylococcal enterotoxins (SEs). SEs include 33 distinct types and multiple sequence variants per SE type. Various mass spectrometry methods have been reported for the detection of SEs using a conventional bottom-up approach. However, the bottom-up approach cannot differentiate between all sequence variants due to partial sequence coverage, and it requires a long trypsin digestion time. While the alternative top-down approach can theoretically identify any sequence modifications, it generally provides lower sensitivity. In this study, we optimized top-down mass spectrometry conditions and incorporated a fully ¹⁵N-labeled SEA spiked early in the protocol to achieve sensitivity and repeatability comparable to bottom-up approaches. After robust immunoaffinity purification of the SEA, mass spectrometry signals were acquired on a Q-Orbitrap instrument operated in full-scan mode and targeted acquisition by parallel reaction monitoring (PRM), enabling the identification of sequence variants and precise quantification of SEA. The protocol was evaluated in liquid and solid dairy products and demonstrated detection limits of 0.5 ng/mL or ng/g in PRM and 1 ng/mL or ng/g in full-scan mode for milk and Roquefort cheese. The top-down method was successfully applied to various dairy products, allowing discrimination of contaminated versus non-contaminated food, quantification of SEA level and identification of the variant involved.

The increasing use of Cannabis sativa products for medicinal, dietary, and recreational purposes has raised concerns about mycotoxin contamination in cannabis and hemp. Mycotoxins persist in these products' post-processing, posing health risks via multiple exposure routes. This study investigated cytotoxic and genotoxic interactions between cannabidiol (CBD) and the mycotoxin citrinin (CIT) using human cell models: SH-SY5Y, HepG2, HEK293, and peripheral blood lymphocytes. IC₅₀ values and membrane disruption were initially assessed, followed by an evaluation of genotoxicity in lymphocytes using the Comet Assay and Cytokinesis Blocked Micronucleus Cytome Assay. Obtained findings demonstrate that cell-type sensitivity varied across treatments, with combined CBD and CIT exposure exhibiting distinct interactions. Lactate dehydrogenase (LDH) release remained minimal, suggesting cytotoxicity did not stem from membrane disruption but likely involved intracellular pathways. In lymphocytes, CBD alone produced negligible cyto/genotoxic effects and weak antiproliferative responses, whereas CIT displayed clear toxic impacts. DNA damage indicates that CIT may induce genome instability through indirect mechanisms rather than direct DNA interaction, with evidence of potential aneuploidic effects from the CBMN Cyt Assay. Combined exposure led to a reduction in CIT-induced DNA and cytogenetic damage, suggesting CIT's potential interference with the beneficial properties of CBD. These results provide a foundation for further toxicological assessments and highlight the necessity of standardized mycotoxin monitoring in cannabis-derived products.

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

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

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

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

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