Synaptic transmission is a fundamental neurobiological process enabling exchange of signals between neurons as well as neurons and their non-neuronal effectors. The complex molecular machinery of the synaptic vesicle cycle and transmitter release has emerged and developed in the course of the evolutionary race, to ensure adaptive gain and survival of the fittest. In parallel, a generous arsenal of biomolecules and neuroactive peptides have co-evolved, which selectively target the transmitter release machinery, with the aim of subduing natural rivals or neutralizing prey. With advances in neuropharmacology and quantitative biology, neurotoxins targeting presynaptic mechanisms have attracted major interest, revealing considerable potential as carriers of molecular cargo and probes for meddling synaptic transmission mechanisms for research and medical benefit. In this review, we investigate and discuss key facets employed by the most prominent bacterial and animal toxins targeting the presynaptic secretory machinery. We explore the cellular basis and molecular grounds for their tremendous potency and selectivity, with effects on a wide range of neural functions. Finally, we consider the emerging preclinical and clinical data advocating the use of active ingredients of neurotoxins for the advancement of molecular medicine and development of restorative therapies.
- Klíčová slova
- Botulinum neurotoxin, Drug delivery, Exocytosis, Molecular medicine, Nano-carriers, Presynaptic, SNARE proteins, Tetanus toxin, Therapeutic targeting,
- MeSH
- biologické toxiny toxicita MeSH
- lidé MeSH
- nervový přenos účinky léků MeSH
- neurotoxiny toxicita MeSH
- neurotransmiterové látky metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- biologické toxiny MeSH
- neurotoxiny MeSH
- neurotransmiterové látky MeSH
The production of toxic plant secondary metabolites (phytotoxins) for defense is a widespread phenomenon in the plant kingdom and is even present in agricultural crops. These phytotoxins may have similar characteristics to anthropogenic micropollutants in terms of persistence and toxicity. However, they are only rarely included in environmental risk assessments, partly because a systematic overview of phytotoxins is missing. Here, we present a newly developed, freely available database, Toxic Plants-PhytoToxins (TPPT), containing 1586 phytotoxins of potential ecotoxicological relevance in Central Europe linked to 844 plant species. Our database summarizes phytotoxin patterns in plant species and provides detailed biological and chemical information as well as in silico estimated properties. Using the database, we evaluated phytotoxins regarding occurrence, approximated from the frequencies of Swiss plant species; environmental behavior based on aquatic persistence and mobility; and toxicity. The assessment showed that over 34% of all phytotoxins are potential aquatic micropollutants and should be included in environmental investigations.
- Klíčová slova
- aquatic pollution, invasive species, natural toxins, poisonous plants, risk assessment,
- MeSH
- biologické toxiny analýza toxicita MeSH
- chemické látky znečišťující vodu analýza toxicita MeSH
- databáze faktografické MeSH
- jedovaté rostliny chemie klasifikace MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické toxiny MeSH
- chemické látky znečišťující vodu MeSH
Biological toxins are a heterogeneous group of compounds that share commonalities with biological and chemical agents. Among them, protein toxins represent a considerable, diverse set. They cover a broad range of molecular weights from less than 1000 Da to more than 150 kDa. This review aims to compare conventional detection methods of protein toxins such as in vitro bioassays with proteomic methods, including immunoassays and mass spectrometry-based techniques and their combination. Special emphasis is given to toxins falling into a group of selected agents, according to the Centers for Disease Control and Prevention, such as Staphylococcal enterotoxins, Bacillus anthracis toxins, Clostridium botulinum toxins, Clostridium perfringens epsilon toxin, ricin from Ricinus communis, Abrin from Abrus precatorius or control of trade in dual-use items in the European Union, including lesser known protein toxins such as Viscumin from Viscum album. The analysis of protein toxins and monitoring for biological threats, i.e., the deliberate spread of infectious microorganisms or toxins through water, food, or the air, requires rapid and reliable methods for the early identification of these agents.
- Klíčová slova
- analytical methods, bio-terrorism, protein toxins, proteomic,
- MeSH
- bakteriální proteiny analýza toxicita MeSH
- biologické toxiny analýza toxicita MeSH
- lidé MeSH
- proteomika metody MeSH
- rostlinné proteiny analýza toxicita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- bakteriální proteiny MeSH
- biologické toxiny MeSH
- rostlinné proteiny MeSH
Massive cyanobacterial water blooms are serious environmental and health problems worldwide. While some cyanobacterial toxins such as peptide microcystins have been investigated extensively, other toxic components of cyanobacteria (e.g. lipopolysaccharides, LPS) are poorly understood. The present study characterized endotoxin activities of LPS isolated from (i) laboratory cyanobacterial cultures, (ii) cyanobacterial water bloom samples dominated by Microcystis sp., Planktothrix sp., Aphanizomenon sp. and Anabaena sp., (iii) heterotrophic Gram-negative bacteria Escherichia coli, Kluyvera intermedia, Pseudomonas putida and Pseudomonas fluorescens and (iv) green alga Pseudokirchneriella subcapitata. Toxicity results derived with Limulus amebocyte lysate assay (LAL-test) showed that endotoxin activities of LPS from both cyanobacteria and heterotrophic bacteria were comparable and the values were within a similar range (1 x 10(3)-1 x 10(6) Endotoxin Units, EU, per mg of isolated LPS). The highest activities among the cyanobacterial samples were observed in the Aphanizomenon sp. dominated water bloom. The results also suggest generally higher endotoxin activities in complex natural samples than in laboratory cyanobacterial cultures. Further, experiments with the eukaryotic green alga P. subcapitata demonstrated a need for careful purification of the LPS extracts prior to testing with the LAL assay as several contaminants may overestimate endotoxin activities. This study shows relatively high pyrogenicity of LPS from various cyanobacteria. Further research should focus on detailed toxicological and ecotoxicological characterization of LPS in massive cyanobacterial water blooms.
- MeSH
- Bacteria chemie MeSH
- biologické toxiny izolace a purifikace toxicita MeSH
- Chlorophyta chemie MeSH
- eutrofizace * MeSH
- sinice chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- biologické toxiny MeSH
The aim of this study was to evaluate the cytoprotective effects upon primary human hepatocytes of silymarin extract and its main flavonolignans following exposure to the cytotoxic actions of model toxins. The conditions for the hepatocyte intoxication were optimised for allyl alcohol, carbon tetrachloride, D-galactosamine and paracetamol. Silymarin extract, silychristin and silydianin did not exert cytotoxicity (10-100 microM), whereas silybin and isosilybin at higher concentrations and after longer incubation periods were cytotoxic. All main flavonolignans of silymarin tested displayed concentration-dependent cytoprotection against the toxic effects of both allyl alcohol and carbon tetrachloride but neither paracetamol nor galactosamine. The best protection was achieved by silydianin and silychristin and to a lesser degree by silymarin, while silybin and isosilybin were less effective. It is concluded that these differing outcomes result from the varying abilities of the Silybum marianum substances tested to stabilize the cell membrane, exert antioxidant properties and exhibit intrinsic toxicity.
- MeSH
- antioxidancia farmakologie MeSH
- Asteraceae chemie MeSH
- bifenylové sloučeniny MeSH
- biologické toxiny toxicita MeSH
- flavonoidy farmakologie MeSH
- galaktosamin metabolismus MeSH
- hepatocyty účinky léků enzymologie MeSH
- kultivované buňky MeSH
- L-laktátdehydrogenasa metabolismus MeSH
- lidé MeSH
- lignany farmakologie MeSH
- neopioidní analgetika farmakologie MeSH
- paracetamol farmakologie MeSH
- pikráty metabolismus MeSH
- propanoly toxicita MeSH
- proteosyntéza MeSH
- rostlinné extrakty toxicita MeSH
- scavengery volných radikálů farmakologie MeSH
- separace buněk MeSH
- terc-butylhydroperoxid toxicita MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 1,1-diphenyl-2-picrylhydrazyl MeSH Prohlížeč
- allyl alcohol MeSH Prohlížeč
- antioxidancia MeSH
- bifenylové sloučeniny MeSH
- biologické toxiny MeSH
- flavonoidy MeSH
- galaktosamin MeSH
- L-laktátdehydrogenasa MeSH
- lignany MeSH
- neopioidní analgetika MeSH
- paracetamol MeSH
- pikráty MeSH
- propanoly MeSH
- rostlinné extrakty MeSH
- scavengery volných radikálů MeSH
- terc-butylhydroperoxid MeSH
The results of the study revealed correlation between the reactogenicity of pertussis vaccines in epidemiological observations and the toxic properties of pertussis bacteria in experiment. Quantitative and qualitative differences were found between the toxic factors in pertussis bacteria depending on their type-specific serological activity. Serotype 1.0.3 microbes exhibit more pronounced toxicity which accounts for the greater reactogenicity of vaccines prepared from this serotype as compared with the preparation produced from the serotype 1.2.3. The obtained results suggest the necessity of considering the greater toxicity of the serotype 1.0.3 in the preparation of pertussis vaccines.
- MeSH
- biologické toxiny biosyntéza toxicita MeSH
- Bordetella pertussis metabolismus patogenita MeSH
- druhová specificita MeSH
- hodnocení léčiv MeSH
- klinické zkoušky jako téma MeSH
- kojenec MeSH
- LD50 MeSH
- lidé MeSH
- lymfocyty účinky léků MeSH
- myši MeSH
- nadledviny patologie MeSH
- pertusová vakcína toxicita MeSH
- počet leukocytů MeSH
- preklinické hodnocení léčiv MeSH
- tělesná hmotnost účinky léků MeSH
- vakcinace škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- srovnávací studie MeSH
- Názvy látek
- biologické toxiny MeSH
- pertusová vakcína MeSH
- MeSH
- antigeny bakteriální analýza MeSH
- bakteriologické techniky MeSH
- biologické toxiny biosyntéza izolace a purifikace toxicita MeSH
- Corynebacterium klasifikace imunologie metabolismus MeSH
- difterický antitoxin MeSH
- difterický toxin biosyntéza izolace a purifikace MeSH
- fagotypizace * MeSH
- geny * MeSH
- Haplorrhini MeSH
- imunodifuze MeSH
- koně imunologie MeSH
- králíci MeSH
- kultivační techniky MeSH
- ledviny MeSH
- lyzogenie MeSH
- morčata MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- morčata MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny bakteriální MeSH
- biologické toxiny MeSH
- difterický antitoxin MeSH
- difterický toxin MeSH
- MeSH
- antitoxiny farmakologie MeSH
- bakteriální proteiny biosyntéza izolace a purifikace MeSH
- bakteriofágy MeSH
- biologické toxiny biosyntéza izolace a purifikace toxicita MeSH
- chromatografie iontoměničová MeSH
- Clostridium perfringens imunologie MeSH
- Corynebacterium klasifikace enzymologie imunologie metabolismus MeSH
- difterický antitoxin terapeutické užití MeSH
- fosfatidylcholiny MeSH
- fosfolipasy biosyntéza toxicita MeSH
- imunodifuze MeSH
- králíci MeSH
- kůže účinky léků MeSH
- lyzogenie MeSH
- morčata MeSH
- nekróza chemicky indukované MeSH
- Staphylococcus imunologie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- morčata MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antitoxiny MeSH
- bakteriální proteiny MeSH
- biologické toxiny MeSH
- difterický antitoxin MeSH
- fosfatidylcholiny MeSH
- fosfolipasy MeSH
- MeSH
- biologické toxiny toxicita MeSH
- endotoxiny toxicita MeSH
- horečka chemicky indukované MeSH
- hydrokortison farmakologie MeSH
- kortison farmakologie MeSH
- kožní manifestace * MeSH
- králíci MeSH
- Salmonella typhi MeSH
- spála MeSH
- Streptococcus MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické toxiny MeSH
- endotoxiny MeSH
- hydrokortison MeSH
- kortison MeSH
