Toxins

21 pages, 614 KiB

Open AccessReview

Residual Kidney Function in Hemodialysis: Its Importance and Contribution to Improved Patient Outcomes

by Yoshitsugu Obi, Jochen G. Raimann, Kamyar Kalantar-Zadeh and Mariana Murea

Toxins 2024, 16(7), 298; https://doi.org/10.3390/toxins16070298 (registering DOI) - 28 Jun 2024

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Individuals afflicted with advanced kidney dysfunction who require dialysis for medical management exhibit different degrees of native kidney function, called residual kidney function (RKF), ranging from nil to appreciable levels. The primary focus of this manuscript is to delve into the concept of [...] Read more.

Individuals afflicted with advanced kidney dysfunction who require dialysis for medical management exhibit different degrees of native kidney function, called residual kidney function (RKF), ranging from nil to appreciable levels. The primary focus of this manuscript is to delve into the concept of RKF, a pivotal yet under-represented topic in nephrology. To begin, we unpack the definition and intrinsic nature of RKF. We then juxtapose the efficiency of RKF against that of hemodialysis in preserving homeostatic equilibrium and facilitating physiological functions. Given the complex interplay of RKF and overall patient health, we shed light on the extent of its influence on patient outcomes, particularly in those living with advanced kidney dysfunction and on dialysis. This manuscript subsequently presents methodologies and measures to assess RKF, concluding with the potential benefits of targeted interventions aimed at preserving RKF. Full article

(This article belongs to the Special Issue Kidney Replacement Therapy by Hemodialysis: 21st Century Challenges)

20 pages, 434 KiB

Open AccessArticle

Vitamin 25(OH)D₃, E, and C Supplementation Impact the Inflammatory and Antioxidant Responses in Piglets Fed a Deoxynivalenol-Contaminated Diet and Challenged with Lipopolysaccharides

by Béatrice Sauvé, Younes Chorfi, Marie-Pierre Létourneau-Montminy and Frédéric Guay

Toxins 2024, 16(7), 297; https://doi.org/10.3390/toxins16070297 (registering DOI) - 28 Jun 2024

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Abstract

Using alternative ingredients or low-quality grain grades to reduce feeding costs for pig diets can introduce mycotoxins such as deoxynivalenol (DON) into feed, which is known to induce anorexia, inflammation, and oxidative stress. Adding vitamin 25(OH)D₃ or vitamins E and C to [...] Read more.

Using alternative ingredients or low-quality grain grades to reduce feeding costs for pig diets can introduce mycotoxins such as deoxynivalenol (DON) into feed, which is known to induce anorexia, inflammation, and oxidative stress. Adding vitamin 25(OH)D₃ or vitamins E and C to the feed could increase piglets’ immune system to alleviate the effects of DON. This study used 54 pigs (7.8 ± 0.14 kg) in 27 pens (2 pigs/pen) with a vitamin 25(OH)D₃ or vitamin E-C supplementation, or their combination, in DON-contaminated (5.1 mg/kg) feed ingredients over 21 days followed by a lipopolysaccharide (LPS) challenge (20 µg/kg BW) 3 h prior to euthanasia for 1 piglet per pen. DON contamination induced anorexia, which reduced piglet growth. DON also induced immunomodulation, oxidative stress, and downregulated vitamin D status. The vitamin E and C supplementation and the combination of vitamins E, C, and 25(OH)D₃ provided protection against DON contamination by not only decreasing blood and liver oxidative stress markers, but also by increasing antioxidant enzymes and tocopherol levels in blood, indicating improved antioxidant defense mechanisms. The combination of vitamins also restored the vitamin D status. After LPS challenge, DON contamination decreased intestinal and liver antioxidant statuses and increased inflammation markers. The addition of vitamins E and C to DON-contaminated feed reduced markers of inflammation and improved the antioxidant status after the LPS immune stimulation. The combination of all these vitamins also reduced the oxidative stress markers and the inflammation in the intestine and mesenteric lymph nodes, suggesting an anti-inflammatory effect. Full article

(This article belongs to the Special Issue Advances in the Effect of Mycotoxin on Lipid Peroxide and Antioxidant Status of Animals)

15 pages, 440 KiB

Open AccessArticle

Validation of a UPLC-MS/MS Method for Multi-Matrix Biomonitoring of Alternaria Toxins in Humans

by Lia Visintin, María García Nicolás, Sarah De Saeger and Marthe De Boevre

Toxins 2024, 16(7), 296; https://doi.org/10.3390/toxins16070296 (registering DOI) - 28 Jun 2024

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Abstract

Mycotoxins, natural toxins produced by fungi, contaminate nearly 80% of global food crops. Alternaria mycotoxins, including alternariol (AOH), alternariol monomethylether (AME), and tenuazonic acid (TeA), present a health concern due to their prevalence in various plants and fruits. Exposure to these toxins exceeds [...] Read more.

Mycotoxins, natural toxins produced by fungi, contaminate nearly 80% of global food crops. Alternaria mycotoxins, including alternariol (AOH), alternariol monomethylether (AME), and tenuazonic acid (TeA), present a health concern due to their prevalence in various plants and fruits. Exposure to these toxins exceeds the threshold of toxicological concern in some European populations, especially infants and toddlers. Despite this, regulatory standards for Alternaria toxins remain absent. The lack of toxicokinetic parameters, reference levels, and sensitive detection methods complicates risk assessment and highlights the necessity for advanced biomonitoring (HBM) techniques. This study addresses these challenges by developing and validating ultra-high performance liquid chromatography method coupled with tandem mass spectrometry to quantify AOH, AME, TeA, and their conjugates in multiple biological matrices. The validated method demonstrates robust linearity, precision, recovery (94–111%), and sensitivity across urine (LOD < 0.053 ng/mL), capillary blood (LOD < 0.029 ng/mL), and feces (LOD < 0.424 ng/g), with significantly lower LOD for TeA compared to existing methodologies. The application of minimally invasive microsampling techniques for the blood collection enhances the potential for large-scale HBM studies. These advancements represent a step toward comprehensive HBM and exposure risk assessments for Alternaria toxins, facilitating the generation of data for regulatory authorities. Full article

(This article belongs to the Special Issue Multi Methods for Detecting Natural Toxins)

12 pages, 455 KiB

Open AccessSystematic Review

Onabotulinumtoxina in the Prevention of Migraine in Pediatric Population: A Systematic Review

by Artemis Mavridi, Aine Redmond, Paraschos Archontakis-Barakakis, Petya Bogdanova-Mihaylova, Christina I. Deligianni, Dimos D. Mitsikostas and Theodoros Mavridis

Toxins 2024, 16(7), 295; https://doi.org/10.3390/toxins16070295 - 28 Jun 2024

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Abstract

Migraine is a leading cause of disability worldwide, yet it remains underrecognized and undertreated, especially in the pediatric and adolescent population. Chronic migraine occurs approximately in 1% of children and adolescents requiring preventive treatment. Topiramate is the only FDA-approved preventative treatment for children [...] Read more.

Migraine is a leading cause of disability worldwide, yet it remains underrecognized and undertreated, especially in the pediatric and adolescent population. Chronic migraine occurs approximately in 1% of children and adolescents requiring preventive treatment. Topiramate is the only FDA-approved preventative treatment for children older than 12 years of age, but there is conflicting evidence regarding its efficacy. OnabotulinumtoxinA is a known and approved treatment for the management of chronic migraine in people older than 18 years. Several studies examine its role in the pediatric population with positive results; however, the clear-cut benefit is still unclear. OnabotulinumtoxinA seems not only to improve disability scores (PedMIDAS) but also to improve the quality, characteristics, and frequency of migraines in the said population. This systematic review aims to summarize the evidence on the efficacy, dosing, administration, long-term outcomes, and safety of onabotulinumtoxinA in pediatric and adolescent migraine. Eighteen studies met the eligibility criteria and were included in this review. The mean monthly migraine days (MMDs), decreased from of 21.2 days per month to 10.7 after treatment. The reported treatment-related adverse effects were mild and primarily injection site related and ranged from 0% to 47.0%. Thus, this review provides compelling evidence suggesting that OnabotulinumtoxinA may represent a safe and effective preventive treatment option for pediatric migraine. Full article

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

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19 pages, 4081 KiB

Open AccessArticle

Effects of Deoxynivalenol and Its Acetylated Derivatives on Lipid Metabolism in Human Normal Hepatocytes

by Zhaoqing Ma, Yuyun He, Yuzhi Li, Qiao Wang, Min Fang, Qing Yang, Zhiyong Gong and Lin Xu

Toxins 2024, 16(7), 294; https://doi.org/10.3390/toxins16070294 - 26 Jun 2024

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Abstract

Deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON) and 15-acetyldeoxynivalenol (15-ADON) belong to type B trichothecenes that are widely detected in agricultural products as one of the most common classes of mycotoxins. In the present study, we aimed to characterize the alteration of lipid metabolism in normal [...] Read more.

Deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON) and 15-acetyldeoxynivalenol (15-ADON) belong to type B trichothecenes that are widely detected in agricultural products as one of the most common classes of mycotoxins. In the present study, we aimed to characterize the alteration of lipid metabolism in normal human hepatocytes by poisoning with DON and its acetylated derivatives. After verifying the hepatotoxicity of the three toxins, DON, 15-ADON, and 3-ADON, the mRNA expression was determined by transcriptomics, and the results showed that DON and 15-ADON had a significant regulatory effect on the transcriptome, in which glycerophospholipid metabolism pathway and phospholipase D signaling pathways have not been reported in studies of DON and its acetylated derivatives. For further validation, we explored lipid metabolism in depth and found that PC (15:0/16:0), PC (16:1/18:3), PC (18:1/22:6), PC (16:0/16:0), PC (16:0/16:1), PC (16:1/18:1), PC (14:0/18:2), PE (14:0/16:0) and PE (18:1/18:3) were downregulated for all nine lipids. Combined with the transcriptome results, we found that hepatic steatosis induced by the three toxins, DON, 15-ADON and 3-ADON, was associated with altered expression of genes related to lipid oxidation, lipogenesis and lipolysis, and their effects on lipid metabolism in L-02 cells were mainly realized through the PC-PE cycle. Full article

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14 pages, 2458 KiB

Open AccessArticle

First Report on Mycotoxin Contamination of Hops (Humulus lupulus L.)

by Ivana Dodlek Šarkanj, Nada Vahčić, Ksenija Markov, Josip Haramija, Natalija Uršulin-Trstenjak, Krunoslav Hajdek, Michael Sulyok, Rudolf Krska and Bojan Šarkanj

Toxins 2024, 16(7), 293; https://doi.org/10.3390/toxins16070293 - 26 Jun 2024

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Abstract

The presence of mycotoxins and other toxic metabolites in hops (Humulus lupulus L.) was assessed for the first time. In total, 62 hop samples were sampled in craft breweries, and analyzed by a multi-toxin LS-MS/MS method. The study collected samples from craft [...] Read more.

The presence of mycotoxins and other toxic metabolites in hops (Humulus lupulus L.) was assessed for the first time. In total, 62 hop samples were sampled in craft breweries, and analyzed by a multi-toxin LS-MS/MS method. The study collected samples from craft breweries in all of the Croatian counties and statistically compared the results. Based on previous reports on Alternaria spp. and Fusarium spp. contamination of hops, the study confirmed the contamination of hops with these toxins. Alternaria toxins, particularly tenuazonic acid, were found in all tested samples, while Fusarium toxins, including deoxynivalenol, were present in 98% of samples. However, no Aspergillus or Penicillium metabolites were detected, indicating proper storage conditions. In addition to the Alternaria and Fusarium toxins, abscisic acid, a drought stress indicator in hops, was also detected, as well as several unspecific metabolites. The findings suggest the need for monitoring, risk assessment, and potential regulation of Alternaria and Fusarium toxins in hops to ensure the safety of hop usage in the brewing and pharmaceutical industries. Also, four local wild varieties were tested, with similar results to the commercial varieties for toxin contamination, but the statistically significant regional differences in toxin occurrence highlight the importance and need for targeted monitoring. Full article

(This article belongs to the Special Issue Novel Approaches in Mycotoxins Research: Detection, Prevention and Mode of Action)

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15 pages, 3556 KiB

Open AccessArticle

Allo-Hemodialysis, a Novel Dialytic Treatment Option for Patients with Kidney Failure: Outcomes of Mathematical Modelling, Prototyping, and Ex Vivo Testing

by Vaibhav Maheshwari, Nadja Grobe, Xin Wang, Amrish Patel, Alhaji Cherif, Xia Tao, Joshua Chao, Alexander Heide, Dejan Nikolic, Jiaming Dong and Peter Kotanko

Toxins 2024, 16(7), 292; https://doi.org/10.3390/toxins16070292 - 26 Jun 2024

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Abstract

It has been estimated that in 2010, over two million patients with end-stage kidney disease may have faced premature death due to a lack of access to affordable renal replacement therapy, mostly dialysis. To address this shortfall in dialytic kidney replacement therapy, we [...] Read more.

It has been estimated that in 2010, over two million patients with end-stage kidney disease may have faced premature death due to a lack of access to affordable renal replacement therapy, mostly dialysis. To address this shortfall in dialytic kidney replacement therapy, we propose a novel, cost-effective, and low-complexity hemodialysis method called allo-hemodialysis (alloHD). With alloHD, instead of conventional hemodialysis, the blood of a patient with kidney failure flows through the dialyzer’s dialysate compartment counter-currently to the blood of a healthy subject (referred to as a “buddy”) flowing through the blood compartment. Along the concentration and hydrostatic pressure gradients, uremic solutes and excess fluid are transferred from the patient to the buddy and subsequently excreted by the healthy kidneys of the buddy. We developed a mathematical model of alloHD to systematically explore dialysis adequacy in terms of weekly standard urea Kt/V. We showed that in the case of an anuric child (20 kg), four 4 h alloHD sessions are sufficient to attain a weekly standard Kt/V of >2.0. In the case of an anuric adult patient (70 kg), six 4 h alloHD sessions are necessary. As a next step, we designed and built an alloHD machine prototype that comprises off-the-shelf components. We then used this prototype to perform ex vivo experiments to investigate the transport of solutes, including urea, creatinine, and protein-bound uremic retention products, and to quantitate the accuracy and precision of the machine’s ultrafiltration control. These experiments showed that alloHD performed as expected, encouraging future in vivo studies in animals with and without kidney failure. Full article

(This article belongs to the Section Uremic Toxins)

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18 pages, 3583 KiB

Open AccessFeature PaperArticle

Blood Lines: Intraspecific and Interspecific Variations in Anticoagulant Actions of Agkistrodon Viperid Venoms

by Francisco C. P. Coimbra, Elda E. Sanchez, Bruno Lomonte, José María Gutiérrez, Juan J. Calvete and Bryan G. Fry

Toxins 2024, 16(7), 291; https://doi.org/10.3390/toxins16070291 - 26 Jun 2024

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Abstract

This study investigated the intraspecific and interspecific variability in the venom effects of Agkistrodon viperid snake species and subspecies (eleven venoms total) on plasma clotting times, fibrinogen levels, and fibrin clot strength. Significant delays in plasma clotting time were observed for A. conanti [...] Read more.

This study investigated the intraspecific and interspecific variability in the venom effects of Agkistrodon viperid snake species and subspecies (eleven venoms total) on plasma clotting times, fibrinogen levels, and fibrin clot strength. Significant delays in plasma clotting time were observed for A. conanti, A. contortrix mokasen, A. contortrix phaeogaster, A. howardgloydi, A. piscivorus leucostoma, and A. piscivorus piscivorus. Notably, the phylogenetically disjunct lineages A. conanti, A. contortrix mokasen, and A. howardgloydi exhibited the most potent anticoagulant effects, indicating the independent amplification of a basal trait. Inhibition assays with the activated clotting enzymes Factors XIa, IXa, Xa, and IIa (thrombin) revealed that FXa inhibition is another basal trait amplified independently on multiple occasions within the genus, but with A. howardgloydi, notably more potent than all others. Phospholipid degradation and zymogen destruction were identified as mechanisms underlying the variability in venom effects observed experimentally and in previous clinical reports. Thromboelastography demonstrated that the venoms did not clot fibrinogen directly but affected fibrin clot strength by damaging fibrinogen and that thrombin was subsequently only able to cleave into weak, unstable clots. The ability to activate Protein C, an endogenous anticoagulant enzyme, varied across species, with some venoms exceeding that of A. contortrix contortrix, which previously yielded the protein diagnostic agent Protac^®. Phylogenetic analysis suggested that both fibrinogen degradation and Protein C activation were each amplified multiple times within the genus, albeit with negative correlation between these two modes of action. This study highlights the evolutionary, clinical, and biodiscovery implications of venom variability in the Agkistrodon species, underscoring their dynamic evolution, emphasising the need for tailored clinical approaches, and highlighting the potential for novel diagnostic and therapeutic developments inspired by the unique properties of snake venoms. Full article

(This article belongs to the Special Issue Venom Components Acting on the Hemostatic System: Structural and Mechanistic Insights)

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Graphical abstract

10 pages, 1689 KiB

Open AccessArticle

Natural Occurrence and Co-Occurrence of Beauvericin and Enniatins in Wheat Kernels from China

by Wenjing Xu, Jiang Liang, Jing Zhang, Yan Song, Xi Zhao, Xiao Liu, Hongyuan Zhang, Haixia Sui, Jin Ye, Yu Wu, Jian Ji, Yongli Ye, Xiulan Sun, Jin Xu, Li Bai, Xiaomin Han and Lei Zhang

Toxins 2024, 16(7), 290; https://doi.org/10.3390/toxins16070290 - 26 Jun 2024

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Abstract

A total of 769 wheat kernels collected from six provinces in China were analyzed for beauvericin (BEA) and four enniatins (ENNs), namely, ENA, ENA₁, ENB and ENB₁, using a solid phase extraction (SPE) technique with ultra-high performance liquid chromatography–tandem [...] Read more.

A total of 769 wheat kernels collected from six provinces in China were analyzed for beauvericin (BEA) and four enniatins (ENNs), namely, ENA, ENA₁, ENB and ENB₁, using a solid phase extraction (SPE) technique with ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). The results show that the predominant toxin was BEA, which had a maximum of 387.67 μg/kg and an average of 37.69 μg/kg. With regard to ENNs, the prevalence and average concentrations of ENB and ENB₁ were higher than those of ENA and ENA₁. The geographical distribution of BEA and ENNs varied. Hubei and Shandong exhibited the highest and lowest positive rates of BEA and ENNs (13.46% and 87.5%, respectively). However, no significant difference was observed among these six provinces. There was a co-occurrence of BEA and ENNs, and 42.26% of samples were simultaneously detected with two or more toxins. Moreover, a significant linear correlation in concentrations was observed between the four ENN analogs (r range: 0.75~0.96, p < 0.05). This survey reveals that the contamination and co-contamination of BEA and ENNs in Chinese wheat kernels were very common. Full article

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11 pages, 404 KiB

Open AccessReview

A Systematic Review of Botulinum Toxin Injection in Pediatric Dystonia

by Andrea Rasera, Giovanna Maddalena Squintani and Maria Angela Cerruto

Toxins 2024, 16(7), 289; https://doi.org/10.3390/toxins16070289 - 26 Jun 2024

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Abstract

Botulinum toxin (BT), a first-line treatment for focal dystonias in adults, has gained USA Food and Drug Administration approval for pediatric upper and lower extremity spasticity and sialorrhea, though its use in children younger than 2 years old is still considered off-label treatment [...] Read more.

Botulinum toxin (BT), a first-line treatment for focal dystonias in adults, has gained USA Food and Drug Administration approval for pediatric upper and lower extremity spasticity and sialorrhea, though its use in children younger than 2 years old is still considered off-label treatment for all pathologies. Dosing, treatment strategies and outcome measures lack international consensus, and they are often extrapolated from adult or spasticity guidelines. This review aims to evaluate the best available evidence on the efficacy and safety of BT therapy in pediatric dystonia (age under 21 years old), isolated or associated with other medical conditions. A comprehensive search in PubMed, Scopus and Web of Science was conducted, including only articles in English. Although no randomized controlled trials are still present, 12 articles were included with an overall of 57 patients. All the papers demonstrate that BT can improve motor function, decrease pain and ameliorate quality of life, with minimal adverse effects in pediatric patients affected by pure or mixed dystonic motor disorders. Despite the low level of evidence, our review shows that BT could be an efficacious treatment for these pediatric patients. The frequent generalized involvement, together with the heterogeneous nature of childhood dystonic forms, sometimes intermingled with spasticity, prompts further multicenter clinical trials or prospective studies with a higher level of evidence to shed light on the efficacy and safety profile of BT in pediatric dystonia. Full article

(This article belongs to the Section Bacterial Toxins)

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13 pages, 750 KiB

Open AccessArticle

Efficacy of Aflatoxin B1 and Fumonisin B1 Adsorption by Maize, Wheat, and Oat Bran

by Youngsun Lee, Jenna M. Lemmetty, Hanna Nihtilä, Hanna Koivula, Serge Samandoulougou, Hagretou Sawadogo-Lingani, Kati Katina and Ndegwa H. Maina

Toxins 2024, 16(7), 288; https://doi.org/10.3390/toxins16070288 - 25 Jun 2024

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Abstract

Mycotoxins, especially aflatoxin B1 (AFB1) and fumonisin B1 (FMB1), are common contaminants in cereal-based foods. Instances of contamination are predicted to increase due to the current challenges induced by climate change. Despite the health benefits of whole grains, the presence of mycotoxins in [...] Read more.

Mycotoxins, especially aflatoxin B1 (AFB1) and fumonisin B1 (FMB1), are common contaminants in cereal-based foods. Instances of contamination are predicted to increase due to the current challenges induced by climate change. Despite the health benefits of whole grains, the presence of mycotoxins in bran remains a concern. Nonetheless, previous research indicates that wheat bran can adsorb mutagens. Therefore, this study investigated the capacity of maize, wheat, and oat brans to adsorb AFB1 and FMB1 under varying in vitro conditions, including pH, binding time, temperature, particle size, and the amount of bran utilized. Maize bran demonstrated a high AFB1 adsorption capacity (>78%) compared to wheat and oat brans. However, FMB1 was not adsorbed by the brans, possibly due to its hydrophilic nature. Lower temperature (≤25 °C) enhanced AFB1 adsorption efficacy in wheat and oat bran, while for maize bran, the highest adsorption occurred at 37 °C. A linear model following Henry’s law best explained AFB1 adsorption by the brans. Further studies identified the pericarp layer of bran as the primary site of AFB1 adsorption, with the initial liquid volume being a critical factor. The study concludes that bran could potentially act as an effective bioadsorbent. Further research is essential to confirm the adsorption efficacy and the bioavailability of AFB1 through in vivo experiments. Full article

(This article belongs to the Special Issue Mitigation and Detoxification Strategies of Mycotoxins)

31 pages, 6616 KiB

Open AccessReview

Cobra Venom Cytotoxins as a Tool for Probing Mechanisms of Mitochondrial Energetics and Understanding Mitochondrial Membrane Structure

by Edward S. Gasanoff and Ruben K. Dagda

Toxins 2024, 16(7), 287; https://doi.org/10.3390/toxins16070287 - 25 Jun 2024

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Abstract

In this paper, we provide an overview of mitochondrial bioenergetics and specific conditions that lead to the formation of non-bilayer structures in mitochondria. Secondly, we provide a brief overview on the structure/function of cytotoxins and how snake venom cytotoxins have contributed to increasing [...] Read more.

In this paper, we provide an overview of mitochondrial bioenergetics and specific conditions that lead to the formation of non-bilayer structures in mitochondria. Secondly, we provide a brief overview on the structure/function of cytotoxins and how snake venom cytotoxins have contributed to increasing our understanding of ATP synthesis via oxidative phosphorylation in mitochondria, to reconcile some controversial aspects of the chemiosmotic theory. Specifically, we provide an emphasis on the biochemical contribution of delocalized and localized proton movement, involving direct transport of protons though the F_o unit of ATP synthase or via the hydrophobic environment at the center of the inner mitochondrial membrane (proton circuit) on oxidative phosphorylation, and how this influences the rate of ATP synthesis. Importantly, we provide new insights on the molecular mechanisms through which cobra venom cytotoxins affect mitochondrial ATP synthesis, mitochondrial structure, and dynamics. Finally, we provide a perspective for the use of cytotoxins as novel pharmacological tools to study membrane bioenergetics and mitochondrial biology, how they can be used in translational research, and their potential therapeutic applications. Full article

(This article belongs to the Section Animal Venoms)

9 pages, 250 KiB

Open AccessReview

Role of Botulinum Toxin in Treatment of Secondary Dystonia: A Case Series and Overview of Literature

by Diksha Mohanty, Heather R. M. Riordan and Peter Hedera

Toxins 2024, 16(7), 286; https://doi.org/10.3390/toxins16070286 - 24 Jun 2024

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Abstract

Introduction: Dystonia can present in primary and secondary forms, depending on co-occurring symptoms and syndromic associations. In contrast to primary dystonia, secondary forms of dystonia are often associated with lesions in the putamen or globus pallidus. Such disorders are commonly neurodegenerative or neurometabolic [...] Read more.

Introduction: Dystonia can present in primary and secondary forms, depending on co-occurring symptoms and syndromic associations. In contrast to primary dystonia, secondary forms of dystonia are often associated with lesions in the putamen or globus pallidus. Such disorders are commonly neurodegenerative or neurometabolic conditions which produce varied neurologic as well as systemic manifestations other than dystonia. Chemo-denervation with botulinum toxin has been successfully used for focal or segmental dystonia. However, studies evaluating the effect of BoNT therapy on patients with secondary dystonia are sparse, given the heterogeneity in etiology and presentation. Methods: We present a series of patients with secondary dystonia who were managed with botulinum toxin therapy. Patients included in this series had a confirmed neurometabolic cause of dystonia. Results: A total of 14 patients, with ages ranging from 17 to 36 years, with disorders including Wilson’s disease, pantothenate kinase-associated neurodegeneration (PKAN), Niemann–Pick disease type C (NPC), glutaric aciduria type 1, Sanfilippo syndrome (Mucopolysaccharidosis Type IIIb), and GM2 gangliosidosis (Sandhoff disease) are presented. Most patients experienced a mild to moderate improvement in treated dystonia with benefits ranging from 6 to 12 weeks, with the median length of the benefits lasting approximately eight weeks, without any significant adverse effects. Conclusion: Although the secondary causes of dystonia are complex and diverse, our presented data and the available reports of the use of botulinum toxin support the conclusion that chemo-denervation plays an important role in symptom alleviation. Full article

(This article belongs to the Special Issue Application of Botulinum Toxins in Non-spastic and Neurodegenerative Disorders)

14 pages, 9547 KiB

Open AccessArticle

Rhein Inhibits Cell Development and Aflatoxin Biosynthesis via Energy Supply Disruption and ROS Accumulation in Aspergillus flavus

by Xiaoyan Wang, Kashif Iqbal Sahibzada, Ruibo Du, Yang Lei, Shan Wei, Na Li, Yuansen Hu and Yangyong Lv

Toxins 2024, 16(7), 285; https://doi.org/10.3390/toxins16070285 - 23 Jun 2024

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Abstract

Aspergillus flavus and its carcinogenic secondary metabolites, aflatoxins, not only cause serious losses in the agricultural economy, but also endanger human health. Rhein, a compound extracted from the Chinese herbal medicine Rheum palmatum L. (Dahuang), exhibits good anti-inflammatory, anti-tumor, and anti-oxidative effects. However, [...] Read more.

Aspergillus flavus and its carcinogenic secondary metabolites, aflatoxins, not only cause serious losses in the agricultural economy, but also endanger human health. Rhein, a compound extracted from the Chinese herbal medicine Rheum palmatum L. (Dahuang), exhibits good anti-inflammatory, anti-tumor, and anti-oxidative effects. However, its effect and underlying mechanisms against Aspergillus flavus have not yet been fully illustrated. In this study, we characterized the inhibition effect of rhein on A. flavus mycelial growth, sporulation, and aflatoxin B₁ (AFB₁) biosynthesis and the potential mechanism using RNA-seq analysis. The results indicate that A. flavus mycelial growth and AFB₁ biosynthesis were significantly inhibited by 50 μM rhein, with a 43.83% reduction in colony diameter and 87.2% reduction in AFB₁ production. The RNA-seq findings demonstrated that the differentially expressed genes primarily participated in processes such as spore formation and development, the maintenance of cell wall and membrane integrity, management of oxidative stress, the regulation of the citric acid cycle, and the biosynthesis of aflatoxin. Biochemical verification experiments further confirmed that 50 μM rhein effectively disrupted cell wall and membrane integrity and caused mitochondrial dysfunction through disrupting energy metabolism pathways, leading to decreased ATP synthesis and ROS accumulation, resulting in impaired aflatoxin biosynthesis. In addition, a pathogenicity test showed that 50 μM rhein inhibited A. flavus spore growth in peanut and maize seeds by 34.1% and 90.4%, while AFB₁ biosynthesis was inhibited by 60.52% and 99.43%, respectively. In conclusion, this research expands the knowledge regarding the antifungal activity of rhein and provides a new strategy to mitigate A. flavus contamination. Full article

(This article belongs to the Special Issue Aspergillus flavus and Aflatoxins (Volume III))

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14 pages, 1468 KiB

Open AccessArticle

Selection of Candidate Monoclonal Antibodies for Therapy of Botulinum Toxin Type A Intoxications

by Natalia A. Zeninskaya, Alena K. Ryabko, Maksim A. Marin, Tatyana I. Kombarova, Maria A. Shkuratova, Methun M. Rogozin, Marina V. Silkina, Yana O. Romanenko, Tatiana A. Ivashchenko, Igor G. Shemyakin and Victoria V. Firstova

Toxins 2024, 16(7), 284; https://doi.org/10.3390/toxins16070284 - 21 Jun 2024

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Abstract

Botulism is one of the most serious food intoxications, manifesting as prolonged paralytic conditions. This disease is usually the result of the consumption of poor quality canned or smoked foods, so the inhabitants of many countries of the world are exposed to the [...] Read more.

Botulism is one of the most serious food intoxications, manifesting as prolonged paralytic conditions. This disease is usually the result of the consumption of poor quality canned or smoked foods, so the inhabitants of many countries of the world are exposed to the risk of this kind of poisoning every year. In view of the severity of poisonings caused by botulinum neurotoxins, monoclonal antibodies (mAbs) show great promise because of their targeting action, lack of allergic reactions and serum sickness. The use of a cocktail of mAbs increases the “functional specificity” of their mixture, allowing them to bind to the active domains of different toxin chains and block their action. In this work, we obtained 14 murine mAbs to the catalytic and receptor-binding domain of botulinum toxin type A. The Sp2/0-Ag14 murine myeloma cell line and splenocytes from immunized mice of the BALB/c line were used as fusion partners. We have shown that the selected cocktail of three antibodies neutralizes native toxin more effectively than antibodies separately—complete neutralization is achieved at a toxin dose of 3LD50 and partial neutralization at 5LD50. We presume that this cocktail may be promising as a prototype for the creation of a therapeutic drug capable of neutralizing the toxin in the blood of patients. Full article

(This article belongs to the Section Bacterial Toxins)

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