Genotoxicity Assessment of Five Tremorgenic Mycotoxins (Fumitremorgen B, Paxilline, Penitrem A, Verruculogen, and Verrucosidin) Produced by Molds Isolated from Fermented Meats

2003 ◽  
Vol 66 (11) ◽  
pp. 2123-2129 ◽  
Author(s):  
MONICA SABATER-VILAR ◽  
SANDRA NIJMEIJER ◽  
JOHANNA FINK-GREMMELS
Keyword(s):  
Human Lymphocytes ◽  
Fungal Species ◽  
Starter Cultures ◽  
In Vitro Assays ◽  
Fungal Metabolites ◽  
End Points ◽  
Safety Testing ◽  
The Central Nervous System ◽  
Toxic Potential

A number of toxinogenic fungal species, particularly producers of tremorgenic mycotoxins, have been isolated from traditional fermented meats. Tremorgenic mycotoxins are a group of fungal metabolites known to act on the central nervous system, causing sustained tremors, convulsions, and death in animals. However, the mode of action of these mycotoxins has not been elucidated in detail, and their genotoxic capacity has hardly been investigated. Because genotoxicity is one of the most prominent toxicological end points in food safety testing, we assessed the genotoxicity of five tremorgenic mycotoxins (fumitremorgen B, paxilline, penitrem A, verrucosidin, and verruculogen) associated with molds found in fermented meats. The mycotoxins were tested in two short-term in vitro assays with the use of different genotoxic end points in different phylogenetic systems (the Ames Salmonella/mammalian-microsome assay and the single-cell gel electrophoresis assay of human lymphocytes). According to the results obtained in this study, all of the investigated mycotoxins except penitrem A exhibited a certain degree of genotoxicity. Verrucosidin appeared to have the highest toxic potential, testing positive in both assays. Verruculogen tested positive in the Salmonella/mammalian-microsome assay, and paxilline and fumitremorgen B caused DNA damage in human lymphocytes. The use of fungal starter cultures to avoid tremorgen contamination in fermented meats is recommended.

scholarly journals Histamine H2 receptor radioligands: triumphs and challenges

2021 ◽  
Author(s):  
Steffen Pockes ◽  
Katharina Tropmann
Keyword(s):  
Receptor Expression ◽  
In Vitro Assays ◽  
Histamine H2 Receptor ◽  
Drug Candidates ◽  
Carbon 14 ◽  
The Central Nervous System ◽  
And Function ◽  
Role And Function

Since the discovery of the histamine H2 receptor (H2R), radioligands were among the most powerful tools to investigate its role and function. Initially, radiolabeling was used to investigate human and rodent tissues regarding their receptor expression. Later, radioligands gained increasing significance as pharmacological tools in in vitro assays. Although tritium-labeling was mainly used for this purpose, labeling with carbon-14 is preferred for metabolic studies of drug candidates. After the more-or-less successful application of numerous labeled H2R antagonists, the recent development of the G protein-biased radioligand [3H]UR-KAT479 represents another step forward to elucidate the widely unknown role of the H2R in the central nervous system through future studies.

scholarly journals Structural and Functional Analysis of Horse Cathelicidin Peptides

2001 ◽  
Vol 45 (3) ◽  
pp. 715-722 ◽  
Author(s):  
Barbara Skerlavaj ◽  
Marco Scocchi ◽  
Renato Gennaro ◽  
Angela Risso ◽  
Margherita Zanetti
Keyword(s):  
Strong Dependence ◽  
Functional Characterization ◽  
Fungal Species ◽  
Helical Conformation ◽  
In Vitro Assays ◽  
Synthetic Analogue ◽  
Salt Medium ◽  
Cdna Sequences ◽  
Low Ionic Strength

ABSTRACT Cathelicidin-derived antimicrobial peptides are a component of the peptide-based host defense of neutrophils and epithelia, with a widespread distribution in mammals. We recently reported the cDNA sequences of three putative horse myeloid cathelicidins, named eCATH-1, -2, and -3. A Western analysis was performed to investigate their presence in neutrophils and processing to mature peptides. eCATH-2 and eCATH-3, but not eCATH-1, were found to be present in uncleaved forms in horse neutrophils. The corresponding mature peptides were detected in inflammatory sites, suggesting that processing of the propeptides takes place upon neutrophil activation. A functional characterization was then performed with synthetic eCATH peptides. Circular dichroism measurements indicated an amphipathic α-helical conformation of these peptides in an anisotropic environment, and in vitro assays revealed a potent activity and a broad spectrum of antimicrobial activity for eCATH-1 and a somewhat more restricted spectrum of activity for eCATH-2. Conversely, a strong dependence on salt concentration was observed when the activity of eCATH-3 was tested. This peptide efficiently killed bacteria and some fungal species, i.e.,Cryptococcus neoformans and Rhodotorula rubra, in low-ionic-strength media, but the activity was inhibited in the presence of physiological salt medium. This behavior could be modified by modulating the amphipathicity of the molecule. In fact, the synthetic analogue LLK-eCATH-3, with a slightly modified sequence that increases the hydrophobic moment of the peptide, displayed a potent activity in physiological salt medium against the strains resistant to eCATH-3 under these conditions.

Evaluation of Genotoxicity of Ampicillin and Carbenicillin on Human Lymphocytes in vitro: Chromosome Aberrations, Mitotic Index, Cell Cycle Kinetics, Satellite Associations of Acrocentric Chromosomes and Sister Chromatid Exchanges

1984 ◽  
Vol 3 (3) ◽  
pp. 173-191 ◽  
Author(s):  
Manjula Jaju ◽  
Madhuri Jaju ◽  
Y.R. Ahuja
Keyword(s):  
Plasma Level ◽  
Mitotic Index ◽  
Chromosome Aberrations ◽  
Human Lymphocytes ◽  
New Drugs ◽  
End Points ◽  
Satellite Associations ◽  
Therapeutic Doses

A large number of drugs have been introduced into man's environment in recent years, many of which have been shown to have mutagenic, teratogenic and carcinogenic effects. Keeping in view the potential hazardous effects of drugs and chemicals, it is desirable to test new drugs for their genotoxic effects prior to widespread use. 1 In the present investigation genetic effects of ampicillin and carbenicillin were studied in vitro in human lymphocytes using a number of end-points. 2 These drugs were added at a range of concentrations and times during a 72h culture period. Concentrations corresponding to the plasma level after receiving therapeutic doses as well as concentrations higher than the plasma levels were examined. 3 Neither drug affected the frequency of chromosome aberrations, satellite associations, mitotic index and cell turnover rate at plasma level concentrations. However, all these parameters were affected at higher concentrations. 4 The frequency of SCEs was not increased with both the drugs irrespective of the concentrations or durations of treatment, suggesting that the mechanisms leading to the formation of SCEs and chromosome aberrations are different. 5 Both ampicillin and carbenicillin were genetically non-toxic for the end points measured and non-clastogenic in vitro at therapeutic doses. However, previous studies have shown ampicillin to be clastogenic in vivo. 6 For evaluation of genetic toxicity, drugs should be tested both in vitro and in vivo.

Synthesis and mutagenicity of 2-aryl-substitute (o-hydroxy-, m-bromo-, o-methoxy-, o-nitro-phenyl or 4-pyridyl) benzothiazole derivatives on Salmonella typhimurium and human lymphocytes exposed in vitro

Biologia ◽  
2007 ◽  
Vol 62 (5) ◽  
Author(s):  
Berrin Ayaz Tuylu ◽  
Hulya Zeytinoglu ◽  
Ilhan Isikdag
Keyword(s):  
Salmonella Typhimurium ◽  
Sister Chromatid ◽  
Ames Test ◽  
Mutagenic Activity ◽  
Human Lymphocytes ◽  
In Vitro Assays ◽  
Benzothiazole Derivatives ◽  
Replication Index ◽  
Derivatives Of

AbstractDerivatives of 2-aryl-substitute (o-hydroxy-, m-bromo-, o-methoxy-, o-nitro-phenyl or 4-pyridyl) benzothiazole were synthesized and tested for their mutagenicity in in vitro assays: (i) in the Ames test with Salmonella typhimurium TA98 and TA100 strains; and (ii) in the sister chromatid exchange (SCE) in cultured human lymphocytes. The four of compounds (BT-11, B-12, BT-14 and BT-15) caused statistically significant increase in revertant colonies of TA98 and TA100. Treatment of lymphocytes with compounds also caused a significant increase in SCE/cell in association with high levels and long exposure (300 µg/mL and 48 h) of the four compounds. It can be concluded that benzothiazole derivatives showed mutagenic activity and were also able to exert a genotoxic effect reducing both the replication index and mitotic index.

Evaluation of the in-vitro Antifungal Activity of Selected Fungal Species Tested Against Opportunistic Human Pathogen Candida albicans

2020 ◽  
Vol 8 (01) ◽  
pp. 01-08
Author(s):  
Aakriti Shukla ◽  
Apoorva Pathak
Keyword(s):  
Candida Albicans ◽  
Fungal Infections ◽  
Bloodstream Infections ◽  
Fungal Species ◽  
Fungal Metabolites ◽  
Antifungal Antibiotics ◽  
Opportunistic Human Pathogen ◽  
Hospital Acquired ◽  
In Vitro Antifungal Activity

Candida albicans is currently the fourth-leading cause of hospital-acquired bloodstream infections, reaching a mortality rate of up to 35–40% for systemic or disseminated infections. Systemic mycoses can occur in patients with severely impaired immune systems (AIDS), with organ or bone marrow transplants, cancer patients undergoing chemotherapy, and patients in ICU (neonates and elderly). It is, therefore, obvious that there is a substantial need for fast, effective antifungal antibiotics to combat fungal infections. The present investigation has been proposed to screen effective fungal metabolites for the control of Candida albicans by evaluating the potential of fungal bioactive compounds, its purification and characterization

Molecular Docking and Quantum Studies of Lawsone Dimers Derivatives: New Investigation of Antioxidant Behavior and Antifungal Activity

2020 ◽  
Vol 20 (3) ◽  
pp. 182-191 ◽  
Author(s):  
Aldo S. de Oliveira ◽  
David L. Palomino-Salcedo ◽  
Eduardo Zapp ◽  
Daniela Brondani ◽  
Thaynara D. Hoppe ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Reducing Power ◽  
Public Health Problem ◽  
Resistance Mechanisms ◽  
Docking Studies ◽  
Fungal Species ◽  
Antioxidant Potential ◽  
In Vitro Assays ◽  
Major Public Health Problem

Background: In general, fungal species are characterized by their opportunistic character and can trigger various infections in immunocompromised hosts. The emergence of infections associated with high mortality rates is due to the resistance mechanisms that these species develop. Methods: This phenomenon of resistance denotes the need for the development of new and effective therapeutic approaches. In this paper, we report the investigation of the antioxidant and antifungal behavior of dimeric naphthoquinones derived from lawsone whose antimicrobial and antioxidant potential has been reported in the literature. Results: Seven fungal strains were tested, and the antioxidant potential was tested using the combination of the methodologies: reducing power, total antioxidant capacity and cyclic voltammetry. Molecular docking studies (PDB ID 5V5Z and 1EA1) were conducted which allowed the derivation of structureactivity relationships (SAR). Compound 1-i, derived from 3-methylfuran-2-carbaldehyde showed the highest antifungal potential with an emphasis on the inhibition of Candida albicans species (MIC = 0.5 µg/mL) and the highest antioxidant potential. Conclusion: A combination of molecular modeling data and in vitro assays can help to find new solutions to this major public health problem.

Alternatives in Safety Testing: Progress or Uselessness?

1994 ◽  
Vol 22 (6) ◽  
pp. 438-444
Author(s):  
Marcel Roberfroid
Keyword(s):  
Intrinsic Property ◽  
Metabolic Activation ◽  
In Vitro Models ◽  
Scientific Data ◽  
Safety Testing ◽  
Metabolic Functions ◽  
Specific Effects ◽  
Organ Specific ◽  
Toxic Potential

Safety testing is a major responsibility of toxicologists. Toxicology is not only a science but also an art. The science of toxicology characterises the toxic potential of a given chemical entity, i.e. the intrinsic property which allows it to react with, and/or to be transformed by, a particular biological system. Based on such scientific data, the art of toxicology has to predict the risk, i.e. the probability that a particular adverse event will occur during a stated period of time or result from a particular challenge. Until now, the science of toxicology has relied almost exclusively on animal tests, the protocols of which are described in directives and regulations. As stated in an Editorial in ATLA (1) the question that toxicologists now have to tackle is, “can non-animal toxicity studies become genuine replacement alternatives …” for assessing risk adequately? Indeed, the science of toxicology has developed, and continues to develop, new approaches (alternatives) to characterise, in well-defined in vitro models (including, for the first time, human models), the toxic potential of chemicals, namely, cytotoxicity, organ-specific effects, modulation of metabolic functions, interference with cell-mediated processes, metabolic activation, etc. But the question remains, what about the art of toxicology? Is it realistic to predict that such new scientific data will, in time, be accepted by regulators for risk evaluation? If these data are to be accepted, we believe that, instead of the present trend towards a regulation-required “protocol toxicology”, toxicologists will have to impose a stepwise decision-tier approach based on the systematic and sequential progression of scientifically justified and rigorously performed investigations, the results of which will be thoroughly and realistically evaluated by experts. It has to be recognised that scientific knowledge has advanced far enough to permit a focus on mechanisms, so that alternatives are fully accepted, no longer as a supplement to a check-list approach, but as a full part of the scientific expertise.

2018 Lush Science Prize

2020 ◽  
Vol 48 (1_suppl) ◽  
pp. 18S-25S
Author(s):  
Jenny McCann ◽  
Terry McCann
Keyword(s):  
Public Awareness ◽  
Relevant Literature ◽  
Toxicity Testing ◽  
In Vitro Assays ◽  
Adverse Outcome Pathway ◽  
Annual Conference ◽  
Animal Testing ◽  
Safety Testing ◽  
Animal Replacement

The Lush Prize supports animal-free testing by awarding money prizes of up to £350,000 per year to the most effective projects and individuals who have been working towards the goal of replacing animals in product or ingredient safety testing. Since its inception in 2012, the Lush Prize has distributed almost £2 million. Prizes are awarded for developments in five strategic areas: Science; Lobbying; Training; Public Awareness; and Young Researchers. In 2015, the judges also awarded a Black Box prize for the development of the skin sensitisation Adverse Outcome Pathway and its associated in vitro assays. The Science Prize is awarded to researchers whose work the judging panel believe to have made the most significant contribution, in the preceding year, to the replacement of animal testing. This 2018 Science Background paper outlines the research projects that were presented to the Prize judges as potential candidates for the 2018 Lush Science Prize award. To obtain an overview of developments in the field of animal replacement in toxicity research, recent work by the relevant scientific institutions and projects in this area, including the OECD, CAAT, ECVAM, UK NC3Rs, US Tox21 Programme, the ToxCast programme and EU-ToxRisk, was reviewed. Recent developments in toxicity testing research were investigated by searching the relevant literature. Abstracts from conferences focusing on animal replacement in toxicity testing that were held in the preceding 12 months, were also analysed, including those from the 2017 10th World Congress on Alternatives and Animals in the Life Sciences and the 2018 Society of Toxicology annual conference.

scholarly journals A Full Set of In Vitro Assays in Chitosan/Tween 80 Microspheres Loaded with Magnetite Nanoparticles

Polymers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 400
Author(s):  
Jorge A Roacho-Pérez ◽  
Kassandra O Rodríguez-Aguillón ◽  
Hugo L Gallardo-Blanco ◽  
María R Velazco-Campos ◽  
Karla V Sosa-Cruz ◽  
...  
Keyword(s):  
Magnetite Nanoparticles ◽  
Protein Delivery ◽  
Cell Damage ◽  
Human Lymphocytes ◽  
Chemical Properties ◽  
Tween 80 ◽  
Biological Behavior ◽  
In Vitro Assays ◽  
Membrane Rupture

Microspheres have been proposed for different medical applications, such as the delivery of therapeutic proteins. The first step, before evaluating the functionality of a protein delivery system, is to evaluate their biological safety. In this work, we developed chitosan/Tween 80 microspheres loaded with magnetite nanoparticles and evaluated cell damage. The formation and physical–chemical properties of the microspheres were determined by FT-IR, Raman, thermogravimetric analysis (TGA), energy-dispersive X-ray spectroscopy (EDS), dynamic light scattering (DLS), and SEM. Cell damage was evaluated by a full set of in vitro assays using a non-cancerous cell line, human erythrocytes, and human lymphocytes. At the same time, to know if these microspheres can load proteins over their surface, bovine serum albumin (BSA) immobilization was measured. Results showed 7 nm magnetite nanoparticles loaded into chitosan/Tween 80 microspheres with average sizes of 1.431 µm. At concentrations from 1 to 100 µg/mL, there was no evidence of changes in mitochondrial metabolism, cell morphology, membrane rupture, cell cycle, nor sister chromatid exchange formation. For each microgram of microspheres 1.8 µg of BSA was immobilized. The result provides the fundamental understanding of the in vitro biological behavior, and safety, of developed microspheres. Additionally, this set of assays can be helpful for researchers to evaluate different nano and microparticles.

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