ijms-logo

Journal Browser

Journal Browser

Special Issue "Natural and Synthetic Toxins: Molecular Aspects and Development Treatment Strategy"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editors

Prof. Dr. Kamil Kuca
E-Mail Website
Guest Editor
1. Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, 50003 Hradec Kralove, Czech Republic
2. Biomedical Research Center, University Hospital Hradec Kralove, 50005 Hradec Kralove, Czech Republic
Interests: drug design and development; antidotes for pesticide and nerve agent intoxications; Alzheimer’s disease; detergents as disinfectants, decontamination means; toxins; nanotechnology; project management; scientific management; technology transfer; health economics and pharmacoeconomics
Special Issues and Collections in MDPI journals
Dr. Eugenie Nepovimova
E-Mail Website
Co-Guest Editor
Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic
Interests: Alzheimer’s disease; Antiaging drugs; Nerve agent antidotes
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous Special Issue "Biochemistry, Molecular Biology and Toxicology of Natural and Synthetic Toxins".

There are many chemical molecules of different origins—natural, semi-natural, or synthetic. Year by year, many novel compounds are synthesized or isolated worldwide. Many of them influence biological systems. Some of them display their effects in a positive way, as promising drug candidates; on the other hand, others exert high toxicity to organisms.

This Special Issue will be focused on both synthetic and naturally-occurring toxins, their chemistry, and their biochemistry. Their effects will be solved at the molecular level (molecular biology and computer modelling). Finally, their toxic potential and possible antidotes used in case of their intoxications will be discussed.

Prof. Kamil Kuca
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • toxins
  • synthetic toxins
  • natural toxins
  • toxic industrial chemicals
  • chemical warfare agents
  • antidotes
  • signaling pathways
  • molecular biology
  • in vitro and in vivo
  • biochemistry

Published Papers (10 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Article
Production and Characterization of Chitooligosaccharides: Evaluation of Acute Toxicity, Healing, and Anti-Inflammatory Actions
Int. J. Mol. Sci. 2021, 22(19), 10631; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910631 - 30 Sep 2021
Viewed by 325
Abstract
The search for promising biomolecules such as chitooligosaccharides (COS) has increased due to the need for healing products that act efficiently, avoiding complications resulting from exacerbated inflammation. Therefore, this study aimed to produce COS in two stages of hydrolysis using chitosanases derived from [...] Read more.
The search for promising biomolecules such as chitooligosaccharides (COS) has increased due to the need for healing products that act efficiently, avoiding complications resulting from exacerbated inflammation. Therefore, this study aimed to produce COS in two stages of hydrolysis using chitosanases derived from Bacillus toyonensis. Additionally, this study aimed to structurally characterize the COS via mass spectrometry, to analyze their biocompatibility in acute toxicity models in vivo, to evaluate their healing action in a cell migration model in vitro, to analyze the anti-inflammatory activity in in vivo models of xylol-induced ear edema and zymosan-induced air pouch, and to assess the wound repair action in vivo. The structural characterization process pointed out the presence of hexamers. The in vitro and in vivo biocompatibility of COS was reaffirmed. The COS stimulated the fibroblast migration. In the in vivo inflammatory assays, COS showed an antiedematogenic response and significant reductions in leukocyte migration, cytokine release, and protein exudate. The COS healing effect in vivo was confirmed by the significant wound reduction after seven days of the experiment. These results indicated that the presence of hexamers influences the COS biological properties, which have potential uses in the pharmaceutical field due to their healing and anti-inflammatory action. Full article
Show Figures

Graphical abstract

Article
Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl
Int. J. Mol. Sci. 2021, 22(6), 3072; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063072 - 17 Mar 2021
Viewed by 515
Abstract
Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered prophylactically before exposure to the OPC paraoxon, are able to protect from its toxic effects. In the present study, we have [...] Read more.
Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered prophylactically before exposure to the OPC paraoxon, are able to protect from its toxic effects. In the present study, we have assessed to what degree experimental (K-27; K-48; K-53; K-74; K-75) or established oximes (pralidoxime, obidoxime), when given as pretreatment at an equitoxic dosage of 25% of LD01, are able to reduce mortality induced by the OPC azinphos-methyl. Their efficacy was compared with that of pyridostigmine, the only FDA-approved substance for such prophylaxis. Efficacy was quantified in rats by Cox analysis, calculating the relative risk of death (RR), with RR=1 for the reference group given only azinphos-methyl, but no prophylaxis. All tested compounds significantly (p ≤ 0.05) reduced azinphos-methyl-induced mortality. In addition, the efficacy of all tested experimental and established oximes except K-53 was significantly superior to the FDA-approved compound pyridostigmine. Best protection was observed for the oximes K-48 (RR = 0.20), K-27 (RR = 0.23), and obidoxime (RR = 0.21), which were significantly more efficacious than pralidoxime and pyridostigmine. The second-best group of prophylactic compounds consisted of K-74 (RR = 0.26), K-75 (RR = 0.35) and pralidoxime (RR = 0.37), which were significantly more efficacious than pyridostigmine. Pretreatment with K-53 (RR = 0.37) and pyridostigmine (RR = 0.52) was the least efficacious. Our present data, together with previous results on other OPCs, indicate that the experimental oximes K-27 and K-48 are very promising pretreatment compounds. When penetration into the brain is undesirable, obidoxime is the most efficacious prophylactic agent already approved for clinical use. Full article
Show Figures

Figure 1

Article
Mass Spectrometry-Based Solid Phase Peptide Reaction Assay for Detecting Allergenicity Using an Immobilized Peptide-Conjugating Photo-Cleavable Linker
Int. J. Mol. Sci. 2020, 21(21), 8332; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218332 - 06 Nov 2020
Viewed by 899
Abstract
The biological process of skin sensitization depends on the ability of a sensitizer to modify endogenous proteins. A direct peptide reactivity assay (DPRA), based on the biological process of skin sensitization, was developed as an alternative to controversial animal experiments. Although DPRA has [...] Read more.
The biological process of skin sensitization depends on the ability of a sensitizer to modify endogenous proteins. A direct peptide reactivity assay (DPRA), based on the biological process of skin sensitization, was developed as an alternative to controversial animal experiments. Although DPRA has been endorsed by industries and is internationally accepted as promising, it has several drawbacks, such as incompatibility with hydrophobic chemicals, inability to perform detailed reaction analysis, and ability to evaluate only single components. Here, we demonstrated that sensitizers and peptide adducts can be easily identified using a mass spectrometry-based solid-phase peptide reaction assay (M-SPRA). We synthesized peptides with a photo-cleavable linker immobilized on resins. We showed the potential of M-SPRA in predicting skin sensitization by measuring the peptide adducts that were selectively eluted from the resin after cleaving the linker post-reaction. M-SPRA provides more detailed information regarding chemical reactivity and accurate assessment of test samples, including mixtures. M-SPRA may be helpful for understanding the binding mechanism of sensitizers (toxicology), which may assist in further refining reactivity assays and aiding in the interpretation of reactivity data. Full article
Show Figures

Graphical abstract

Article
Transcriptome Sequencing Revealed an Inhibitory Mechanism of Aspergillus flavus Asexual Development and Aflatoxin Metabolism by Soy-Fermenting Non-Aflatoxigenic Aspergillus
Int. J. Mol. Sci. 2020, 21(19), 6994; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21196994 - 23 Sep 2020
Cited by 2 | Viewed by 855
Abstract
Aflatoxins (AFs) have always been regarded as the most effective carcinogens, posing a great threat to agriculture, food safety, and human health. Aspergillus flavus is the major producer of aflatoxin contamination in crops. The prevention and control of A. flavus and aflatoxin continues [...] Read more.
Aflatoxins (AFs) have always been regarded as the most effective carcinogens, posing a great threat to agriculture, food safety, and human health. Aspergillus flavus is the major producer of aflatoxin contamination in crops. The prevention and control of A. flavus and aflatoxin continues to be a global problem. In this study, we demonstrated that the cell-free culture filtrate of Aspergillus oryzae and a non-aflatoxigenic A. flavus can effectively inhibit the production of AFB1 and the growth and reproduction of A. flavus, indicating that both of the non-aflatoxigenic Aspergillus strains secrete inhibitory compounds. Further transcriptome sequencing was performed to analyze the inhibitory mechanism of A. flavus treated with fermenting cultures, and the results revealed that genes involved in the AF biosynthesis pathway and other biosynthetic gene clusters were significantly downregulated, which might be caused by the reduced expression of specific regulators, such as AflS, FarB, and MtfA. The WGCNA results further revealed that genes involved in the TCA cycle and glycolysis were potentially involved in aflatoxin biosynthesis. Our comparative transcriptomics also revealed that two conidia transcriptional factors, brlA and abaA, were found to be significantly downregulated, which might lead to the downregulation of conidiation-specific genes, such as the conidial hydrophobins genes rodA and rodB. In summary, our research provides new insights for the molecular mechanism of controlling AF synthesis to control the proliferation of A. flavus and AF pollution. Full article
Show Figures

Figure 1

Article
Oxidative Stress and Analysis of Selected SNPs of ACHE (rs 2571598), BCHE (rs 3495), CAT (rs 7943316), SIRT1 (rs 10823108), GSTP1 (rs 1695), and Gene GSTM1, GSTT1 in Chronic Organophosphates Exposed Groups from Cameroon and Pakistan
Int. J. Mol. Sci. 2020, 21(17), 6432; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176432 - 03 Sep 2020
Cited by 3 | Viewed by 981
Abstract
The detrimental effects of organophosphates (OPs) on human health are thought to be of systemic, i.e., irreversible inhibition of acetylcholinesterase (AChE) at nerve synapses. However, several studies have shown that AChE inhibition alone cannot explain all the toxicological manifestations in prolonged exposure to [...] Read more.
The detrimental effects of organophosphates (OPs) on human health are thought to be of systemic, i.e., irreversible inhibition of acetylcholinesterase (AChE) at nerve synapses. However, several studies have shown that AChE inhibition alone cannot explain all the toxicological manifestations in prolonged exposure to OPs. The present study aimed to assess the status of antioxidants malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) (reduced), catalase, and ferric reducing antioxidant power (FRAP) in chronic OP-exposed groups from Cameroon and Pakistan. Molecular analysis of genetic polymorphisms (SNPs) of glutathione transferases (GSTM1, GSTP1, GSTT1), catalase gene (CAT, rs7943316), sirtuin 1 gene (SIRT1, rs10823108), acetylcholinesterase gene (ACHE, rs2571598), and butyrylcholinesterase gene (BCHE, rs3495) were screened in the OP-exposed individuals to find the possible causative association with oxidative stress and toxicity. Cholinesterase and antioxidant activities were measured by colorimetric methods using a spectrophotometer. Salting-out method was employed for DNA extraction from blood followed by restriction fragment length polymorphism (RFLP) for molecular analysis. Cholinergic enzymes were significantly decreased in OP-exposed groups. Catalase and SOD were decreased and MDA and FRAP were increased in OP-exposed groups compared to unexposed groups in both groups. GSH was decreased only in Pakistani OPs-exposed group. Molecular analysis of ACHE, BCHE, Catalase, GSTP1, and GSTM1 SNPs revealed a tentative association with their phenotypic expression that is level of antioxidant and cholinergic enzymes. The study concludes that chronic OPs exposure induces oxidative stress which is associated with the related SNP polymorphism. The toxicogenetics of understudied SNPs were examined for the first time to our understanding. The findings may lead to a newer area of investigation on OPs induced health issues and toxicogenetics. Full article
Show Figures

Figure 1

Article
Evaluation of the Individual and Combined Toxicity of Fumonisin Mycotoxins in Human Gastric Epithelial Cells
Int. J. Mol. Sci. 2020, 21(16), 5917; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21165917 - 18 Aug 2020
Cited by 8 | Viewed by 972
Abstract
Fumonisin contaminates food and feed extensively throughout the world, causing chronic and acute toxicity in human and animals. Currently, studies on the toxicology of fumonisins mainly focus on fumonisin B1 (FB1). Considering that FB1, fumonisin B2 (FB2) and fumonisin B3 (FB3) could coexist [...] Read more.
Fumonisin contaminates food and feed extensively throughout the world, causing chronic and acute toxicity in human and animals. Currently, studies on the toxicology of fumonisins mainly focus on fumonisin B1 (FB1). Considering that FB1, fumonisin B2 (FB2) and fumonisin B3 (FB3) could coexist in food and feed, a study regarding a single toxin, FB1, may not completely reflect the toxicity of fumonisin. The gastrointestinal tract is usually exposed to these dietary toxins. In our study, the human gastric epithelial cell line (GES-1) was used as in vitro model to evaluate the toxicity of fumonisin. Firstly, we found that they could cause a decrease in cell viability, and increase in membrane leakage, cell death and the induction of expression of markers for endoplasmic reticulum (ER) stress. Their toxicity potency rank is FB1 > FB2 >> FB3. The results also showed that the synergistic effect appeared in the combinations of FB1 + FB2 and FB1 + FB3. Nevertheless, the combinations of FB2 + FB3 and FB1 + FB2 + FB3 showed a synergistic effect at low concentration and an antagonistic effect at high concentration. We also found that myriocin (ISP-1) could alleviate the cytotoxicity induced by fumonisin in GES-1 cells. Finally, this study may help to determine or optimize the legal limits and risk assessment method of mycotoxins in food and feed and provide a potential method to block the fumonisin toxicity. Full article
Show Figures

Figure 1

Review

Jump to: Research

Review
Chemistry and Toxicology of Major Bioactive Substances in Inocybe Mushrooms
Int. J. Mol. Sci. 2021, 22(4), 2218; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042218 - 23 Feb 2021
Cited by 3 | Viewed by 1104
Abstract
Mushroom poisoning has always been a threat to human health. There are a large number of reports about ingestion of poisonous mushrooms every year around the world. It attracts the attention of researchers, especially in the aspects of toxin composition, toxic mechanism and [...] Read more.
Mushroom poisoning has always been a threat to human health. There are a large number of reports about ingestion of poisonous mushrooms every year around the world. It attracts the attention of researchers, especially in the aspects of toxin composition, toxic mechanism and toxin application in poisonous mushroom. Inocybe is a large genus of mushrooms and contains toxic substances including muscarine, psilocybin, psilocin, aeruginascin, lectins and baeocystin. In order to prevent and remedy mushroom poisoning, it is significant to clarify the toxic effects and mechanisms of these bioactive substances. In this review article, we summarize the chemistry, most known toxic effects and mechanisms of major toxic substances in Inocybe mushrooms, especially muscarine, psilocybin and psilocin. Their available toxicity data (different species, different administration routes) published formerly are also summarized. In addition, the treatment and medical application of these toxic substances in Inocybe mushrooms are also discussed. We hope that this review will help understanding of the chemistry and toxicology of Inocybe mushrooms as well as the potential clinical application of its bioactive substances to benefit human beings. Full article
Show Figures

Figure 1

Review
Special Delivery: Potential Mechanisms of Botulinum Neurotoxin Uptake and Trafficking within Motor Nerve Terminals
Int. J. Mol. Sci. 2020, 21(22), 8715; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228715 - 18 Nov 2020
Cited by 2 | Viewed by 1172
Abstract
Botulinum neurotoxins (BoNTs) are highly potent, neuroparalytic protein toxins that block the release of acetylcholine from motor neurons and autonomic synapses. The unparalleled toxicity of BoNTs results from the highly specific and localized cleavage of presynaptic proteins required for nerve transmission. Currently, the [...] Read more.
Botulinum neurotoxins (BoNTs) are highly potent, neuroparalytic protein toxins that block the release of acetylcholine from motor neurons and autonomic synapses. The unparalleled toxicity of BoNTs results from the highly specific and localized cleavage of presynaptic proteins required for nerve transmission. Currently, the only pharmacotherapy for botulism is prophylaxis with antitoxin, which becomes progressively less effective as symptoms develop. Treatment for symptomatic botulism is limited to supportive care and artificial ventilation until respiratory function spontaneously recovers, which can take weeks or longer. Mechanistic insights into intracellular toxin behavior have progressed significantly since it was shown that toxins exploit synaptic endocytosis for entry into the nerve terminal, but fundamental questions about host-toxin interactions remain unanswered. Chief among these are mechanisms by which BoNT is internalized into neurons and trafficked to sites of molecular toxicity. Elucidating how receptor-bound toxin is internalized and conditions under which the toxin light chain engages with target SNARE proteins is critical for understanding the dynamics of intoxication and identifying novel therapeutics. Here, we discuss the implications of newly discovered modes of synaptic vesicle recycling on BoNT uptake and intraneuronal trafficking. Full article
Show Figures

Figure 1

Review
Molecular Aspects of Mycotoxins—A Serious Problem for Human Health
Int. J. Mol. Sci. 2020, 21(21), 8187; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218187 - 31 Oct 2020
Cited by 13 | Viewed by 1555
Abstract
Mycotoxins are toxic fungal secondary metabolities formed by a variety of fungi (moulds) species. Hundreds of potentially toxic mycotoxins have been already identified and are considered a serious problem in agriculture, animal husbandry, and public health. A large number of food-related products and [...] Read more.
Mycotoxins are toxic fungal secondary metabolities formed by a variety of fungi (moulds) species. Hundreds of potentially toxic mycotoxins have been already identified and are considered a serious problem in agriculture, animal husbandry, and public health. A large number of food-related products and beverages are yearly contaminated by mycotoxins, resulting in economic welfare losses. Mycotoxin indoor environment contamination is a global problem especially in less technologically developed countries. There is an ongoing effort in prevention of mould growth in the field and decontamination of contaminated food and feed in order to protect human and animal health. It should be emphasized that the mycotoxins production by fungi (moulds) species is unavoidable and that they are more toxic than pesticides. Human and animals are exposed to mycotoxin via food, inhalation, or contact which can result in many building-related illnesses including kidney and neurological diseases and cancer. In this review, we described in detail the molecular aspects of main representatives of mycotoxins, which are serious problems for global health, such as aflatoxins, ochratoxin A, T-2 toxin, deoxynivalenol, patulin, and zearalenone. Full article
Show Figures

Figure 1

Review
Flakka: New Dangerous Synthetic Cathinone on the Drug Scene
Int. J. Mol. Sci. 2020, 21(21), 8185; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218185 - 31 Oct 2020
Cited by 1 | Viewed by 1276
Abstract
New psychoactive substances are being used as drugs and appear to be quite popular nowadays. Thanks to their specific properties, these drugs create inimitable experiences for intoxicated people. Synthetic cathinones are the most common compounds in these new drugs. Among them, α-pyrrolidopentadione (α-PVP), [...] Read more.
New psychoactive substances are being used as drugs and appear to be quite popular nowadays. Thanks to their specific properties, these drugs create inimitable experiences for intoxicated people. Synthetic cathinones are the most common compounds in these new drugs. Among them, α-pyrrolidopentadione (α-PVP), or “Flakka” (street name), is one of the most famous cathinone-designed drugs. Similar to other synthetic cathinone drugs, α-PVP can effectively inhibit norepinephrine and dopamine transmitters. The adverse reactions of α-PVP mainly include mania, tachycardia, and hallucinations. An increasing number of people are being admitted to emergency wards due to the consequences of their use. This work mainly summarizes the history, synthesis, pharmacology, toxicology, structure–activity relationship, metabolism, clinical process and health risks, poisoning and death, forensic toxicology, and legal status of α-PVP. We hope this review will help bring more attention to the exploration of this substance in order to raise awareness of its negative impacts on humans. Full article
Show Figures

Figure 1

Back to TopTop