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Toxins
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Toxicity of Plant Derived Substances
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Toxicity of Plant Derived Substances

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Plant Toxins".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 41859

Special Issue Editor

Prof. Kateřina Macáková

E-Mail Website
Guest Editor
Department of Pharmacognosy, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
Interests: (Poly)phenolic substances, transition metals, oxidative stress, platelet aggregation, pharmacognosy

Special Issue Information

The plant kingdom is an almost inexhaustible source of various substances that can have both positive and negative effects on the human body. Many natural substances used in the therapy of various diseases come from toxic plant species. These include, for example, cytostatic agents, cardiac glycosides, or anti-Alzheimer´s disease drugs. On the other hand, there are a lot of substances isolated from plants that are commonly used, and whose negative effects or even toxicity is not so obvious (e.g., these effects can occur after prolonged use or is idiosyncratic, etc.). In addition, these substances, although under certain circumstances toxic, may also have significant importance in the search for potential drugs.

This Special Issue aims to collect novel data on toxic or potentially toxic natural substances derived from plant organisms that could a) have negative or toxic effects on human beings and/or b) find application in the treatment of various diseases. Original papers, short communications, reviews, or mini-reviews are welcome for publication.

Prof. Kateřina Macáková
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 submissions that pass pre-check are 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 double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • Natural Substance
  • Plant
  • Toxic
  • Potentially Toxic
  • Potential Drug

Published Papers (5 papers)

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Research

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10 pages, 2297 KiB  
Article
Can Isoquinoline Alkaloids Affect Platelet Aggregation in Whole Human Blood?
by Mst Shamima Parvin, Marcel Hrubša, Jaka Fadraersada, Alejandro Carazo, Jana Karlíčková, Lucie Cahlíková, Jakub Chlebek, Kateřina Macáková and Přemysl Mladěnka
Toxins 2022, 14(7), 491; https://doi.org/10.3390/toxins14070491 - 15 Jul 2022
Cited by 3 | Viewed by 1591
Abstract
Isoquinoline alkaloids have multiple biological activities, which might be associated with positive pharmacological effects as well as negative adverse reactions. As bleeding was suggested to be a side effect of the isoquinoline alkaloid berberine, we decided to ascertain if different isoquinoline alkaloids could [...] Read more.
Isoquinoline alkaloids have multiple biological activities, which might be associated with positive pharmacological effects as well as negative adverse reactions. As bleeding was suggested to be a side effect of the isoquinoline alkaloid berberine, we decided to ascertain if different isoquinoline alkaloids could influence hemocoagulation through the inhibition of either platelet aggregation or blood coagulation. Initially, a total of 14 compounds were screened for antiplatelet activity in whole human blood by impedance aggregometry. Eight of them demonstrated an antiplatelet effect against arachidonic acid-induced aggregation. Papaverine and bulbocapnine were the most potent compounds with biologically relevant IC50 values of 26.9 ± 12.2 μM and 30.7 ± 5.4 μM, respectively. Further testing with the same approach confirmed their antiplatelet effects by employing the most physiologically relevant inducer of platelet aggregation, collagen, and demonstrated that bulbocapnine acted at the level of thromboxane receptors. None of the alkaloids tested had an effect on blood coagulation measured by a mechanical coagulometer. In conclusion, the observed antiplatelet effects of isoquinoline alkaloids were found mostly at quite high concentrations, which means that their clinical impact is most likely low. Bulbocapnine was an exception. It proved to be a promising antiplatelet molecule, which may have biologically relevant effects. Full article
(This article belongs to the Special Issue Toxicity of Plant Derived Substances)
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15 pages, 3362 KiB  
Article
Protective Effect of Nebivolol against Oxidative Stress Induced by Aristolochic Acids in Endothelial Cells
by Marie-Hélène Antoine, Cécile Husson, Tatiana Yankep, Souhaila Mahria, Vanessa Tagliatti, Jean-Marie Colet and Joëlle Nortier
Toxins 2022, 14(2), 132; https://doi.org/10.3390/toxins14020132 - 10 Feb 2022
Cited by 1 | Viewed by 2122
Abstract
Aristolochic acids (AAs) are powerful nephrotoxins that cause severe tubulointerstitial fibrosis. The biopsy-proven peritubular capillary rarefaction may worsen the progression of renal lesions via tissue hypoxia. As we previously observed the overproduction of reactive oxygen species (ROS) by cultured endothelial cells exposed to [...] Read more.
Aristolochic acids (AAs) are powerful nephrotoxins that cause severe tubulointerstitial fibrosis. The biopsy-proven peritubular capillary rarefaction may worsen the progression of renal lesions via tissue hypoxia. As we previously observed the overproduction of reactive oxygen species (ROS) by cultured endothelial cells exposed to AA, we here investigated in vitro AA-induced metabolic changes by 1H-NMR spectroscopy on intracellular medium and cell extracts. We also tested the effects of nebivolol (NEB), a β-blocker agent exhibiting antioxidant properties. After 24 h of AA exposure, significantly reduced cell viability and intracellular ROS overproduction were observed in EAhy926 cells; both effects were counteracted by NEB pretreatment. After 48 h of exposure to AA, the most prominent metabolite changes were significant decreases in arginine, glutamate, glutamine and glutathione levels, along with a significant increase in the aspartate, glycerophosphocholine and UDP-N-acetylglucosamine contents. NEB pretreatment slightly inhibited the changes in glutathione and glycerophosphocholine. In the supernatants from exposed cells, a decrease in lactate and glutamate levels, together with an increase in glucose concentration, was found. The AA-induced reduction in glutamate was significantly inhibited by NEB. These findings confirm the involvement of oxidative stress in AA toxicity for endothelial cells and the potential benefit of NEB in preventing endothelial injury. Full article
(This article belongs to the Special Issue Toxicity of Plant Derived Substances)
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Review

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25 pages, 1770 KiB  
Review
Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern
by Rita Roque Bravo, Ana Carolina Faria, Andreia Machado Brito-da-Costa, Helena Carmo, Přemysl Mladěnka, Diana Dias da Silva, Fernando Remião and on behalf of The OEMONOM Researchers
Toxins 2022, 14(4), 278; https://doi.org/10.3390/toxins14040278 - 13 Apr 2022
Cited by 35 | Viewed by 23242
Abstract
Cocaine is one of the most consumed stimulants throughout the world, as official sources report. It is a naturally occurring sympathomimetic tropane alkaloid derived from the leaves of Erythroxylon coca, which has been used by South American locals for millennia. Cocaine can [...] Read more.
Cocaine is one of the most consumed stimulants throughout the world, as official sources report. It is a naturally occurring sympathomimetic tropane alkaloid derived from the leaves of Erythroxylon coca, which has been used by South American locals for millennia. Cocaine can usually be found in two forms, cocaine hydrochloride, a white powder, or ‘crack’ cocaine, the free base. While the first is commonly administered by insufflation (‘snorting’) or intravenously, the second is adapted for inhalation (smoking). Cocaine can exert local anaesthetic action by inhibiting voltage-gated sodium channels, thus halting electrical impulse propagation; cocaine also impacts neurotransmission by hindering monoamine reuptake, particularly dopamine, from the synaptic cleft. The excess of available dopamine for postsynaptic activation mediates the pleasurable effects reported by users and contributes to the addictive potential and toxic effects of the drug. Cocaine is metabolised (mostly hepatically) into two main metabolites, ecgonine methyl ester and benzoylecgonine. Other metabolites include, for example, norcocaine and cocaethylene, both displaying pharmacological action, and the last one constituting a biomarker for co-consumption of cocaine with alcohol. This review provides a brief overview of cocaine’s prevalence and patterns of use, its physical-chemical properties and methods for analysis, pharmacokinetics, pharmacodynamics, and multi-level toxicity. Full article
(This article belongs to the Special Issue Toxicity of Plant Derived Substances)
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12 pages, 16813 KiB  
Review
Khat, a Cultural Chewing Drug: A Toxicokinetic and Toxicodynamic Summary
by Bárbara Silva, Jorge Soares, Carolina Rocha-Pereira, Přemysl Mladěnka, Fernando Remião and on behalf of The OEMONOM Researchers
Toxins 2022, 14(2), 71; https://doi.org/10.3390/toxins14020071 - 20 Jan 2022
Cited by 16 | Viewed by 10469
Abstract
Khat (Catha edulis) is a recreational, chewed herbal drug that has been used as a psychostimulant for centuries in East Africa and the Arabian Peninsula, namely in Somalia, Ethiopia, and Yemen. However, the growing worldwide availability of khat has produced widespread [...] Read more.
Khat (Catha edulis) is a recreational, chewed herbal drug that has been used as a psychostimulant for centuries in East Africa and the Arabian Peninsula, namely in Somalia, Ethiopia, and Yemen. However, the growing worldwide availability of khat has produced widespread concern. The plant comprises a large number of active substances, among which cathinone, cathine, and norephedrine are the main constituents, which can be included in the group of sympathomimetics of natural origin. In fact, these compounds are amphetamine analogues, and, as such, they have amphetamine-like nervous system stimulant effects. Chewing the leaves gives people a sensation of well-being and increases energy, alertness, and self-confidence. The chronic use of khat is, however, associated with severe cardiac, neurological, psychological, and gastrointestinal complications. The psychological dependence and withdrawal symptoms of khat are the reasons for its prolonged use. The aim of this paper is to review current knowledge on the khat plant with toxicokinetic and toxicodynamic perspectives. Namely, this review paper addresses in vitro, in vivo, and human studies. The models used, as well as the concentrations and doses with the respective biological effects, are discussed. Additionally, the main drug interactions involved with khat are described. Full article
(This article belongs to the Special Issue Toxicity of Plant Derived Substances)
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21 pages, 1113 KiB  
Review
Overview of Pharmacokinetics and Liver Toxicities of Radix Polygoni Multiflori
by Dan Li, Mengbi Yang and Zhong Zuo
Toxins 2020, 12(11), 729; https://doi.org/10.3390/toxins12110729 - 21 Nov 2020
Cited by 15 | Viewed by 3551
Abstract
Radix Polygoni Multiflori (RPM), a traditional Chinese medicine, has been used as a tonic and an anti-aging remedy for centuries. However, its safe and effective application in clinical practice could be hindered by its liver injury potential and lack of investigations on its [...] Read more.
Radix Polygoni Multiflori (RPM), a traditional Chinese medicine, has been used as a tonic and an anti-aging remedy for centuries. However, its safe and effective application in clinical practice could be hindered by its liver injury potential and lack of investigations on its hepatotoxicity mechanism. Our current review aims to provide a comprehensive overview and a critical assessment of the absorption, distribution, metabolism, excretion of RPM, and their relationships with its induced liver injury. Based on the well-reported intrinsic liver toxicity of emodin, one of the major components in RPM, it is concluded that its plasma and liver concentrations could attribute to RPM induced liver injury via metabolic enzymes alteration, hepatocyte apoptosis, bile acids homeostasis disruption, and inflammatory damage. Co-administered 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside in RPM and other drugs/herbs could further aggravate the hepatotoxicity of emodin via enhancing its absorption and inhibiting its metabolism. To ensure the safe clinical use of RPM, a better understanding of the toxicokinetics and effect of its co-occurring components or other co-administered drugs/herbs on the pharmacokinetics of emodin is warranted. Full article
(This article belongs to the Special Issue Toxicity of Plant Derived Substances)
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