Mycotoxin mechanisms of action and health impact: ‘in vitro’ or ‘in vivo’ tests, that is the question

2015 ◽  
Vol 8 (5) ◽  
pp. 573-589 ◽  
Author(s):  
F. Cheli ◽  
C. Giromini ◽  
A. Baldi
Keyword(s):  
Health Effects ◽  
Health Impact ◽  
In Vitro Models ◽  
Mechanisms Of Action ◽  
Animal Testing ◽  
Suitable Alternative ◽  
In Vivo Tests ◽  
Contaminated Food

The aim of this paper is to present examples of in vitro and in vivo tests for mycotoxin mechanisms of action and evaluation of health effects, with a focus on the gut environment and toxicity testing. In vivo investigations may provide information on the net effects of mycotoxins in whole animals, whereas in vitro models represent effective tools to perform simplified experiments under uniform and well-controlled conditions and a suitable alternative to in vivo animal testing providing insights not achievable with animal studies. The main limits of in vitro models are the lack of interactions with other cells and extracellular factors, lack of hormonal or immunological influences, and lack or different levels of in vitro expression of genes involved in the overall response to mycotoxins. The translation of in vitro data into meaningful in vivo effects remains an unsolved problem. The main issues to be considered are the mycotoxin concentration range in accordance with levels encountered in realistic situations, the identification of reliable biomarkers of mycotoxin toxicity, the measurement of the chronic toxicity, the evaluation of single- or multi-toxin challenge. The gastrointestinal wall is the first barrier preventing the entry of undesirable substances. The intestinal epithelium can be exposed to high concentrations of mycotoxins upon ingestion of contaminated food and the amount of mycotoxin consumed via food does not always reflect the amount available to exert toxic actions in a target organ. In vitro digestion models in combination with intestinal epithelial cells are powerful tools to screen and predict the in vivo bioavailability and digestibility of mycotoxins in contaminated food and correctly estimate health effects. In conclusion, in vitro and in vivo tests are complementary approaches for providing a more accurate picture of the health impact of mycotoxins and improved understanding and evaluation of relevant dietary exposure and risk scenarios.

In Vitro Methods as a Tool in Neurotoxicity Studies

1995 ◽  
Vol 23 (4) ◽  
pp. 491-496
Author(s):  
Hanna Tähti ◽  
Leila Vaalavirta ◽  
Tarja Toimela
Keyword(s):  
Risk Evaluation ◽  
Toxicity Testing ◽  
In Vitro Models ◽  
In Vitro Tests ◽  
Industrial Chemicals ◽  
Mercury Compounds ◽  
Toxicological Data ◽  
In Vivo Tests

— There are several hundred industrial chemicals with neurotoxic potential. The neurotoxic risks of most of these chemicals are unknown. Additional methods are needed to assess the risks more effectively and to elucidate the mechanisms of neurotoxicity more accurately than is possible with the conventional methods. This paper deals with general tasks concerning the use of in vitro models in the evaluation of neurotoxic risks. It is based on our previous studies with various in vitro models and on recent literature. The induction of glial fibrillary acidic protein in astrocyte cultures after treatment with known neurotoxicants (mercury compounds and aluminium) is discussed in more detail as an important response which can be detected in vitro. When used appropriately with in vivo tests and with previous toxicological data, in vitro neurotoxicity testing considerably improves risk assessment. The incorporation of in vitro tests into the early stages of risk evaluation can reduce the number of animals used in routine toxicity testing, by identifying chemicals with high neurotoxic potential.

scholarly journals In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5583
Author(s):  
Guilherme Ribeiro Romualdo ◽  
Kaat Leroy ◽  
Cícero Júlio Silva Costa ◽  
Gabriel Bacil Prata ◽  
Bart Vanderborght ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
In Vitro Models ◽  
Virus Infections ◽  
Alcoholic Fatty Liver ◽  
Contaminated Food ◽  
Patient Prognosis ◽  
Key Events ◽  
Translational Modeling

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related death globally. HCC is a complex multistep disease and usually emerges in the setting of chronic liver diseases. The molecular pathogenesis of HCC varies according to the etiology, mainly caused by chronic hepatitis B and C virus infections, chronic alcohol consumption, aflatoxin-contaminated food, and non-alcoholic fatty liver disease associated with metabolic syndrome or diabetes mellitus. The establishment of HCC models has become essential for both basic and translational research to improve our understanding of the pathophysiology and unravel new molecular drivers of this disease. The ideal model should recapitulate key events observed during hepatocarcinogenesis and HCC progression in view of establishing effective diagnostic and therapeutic strategies to be translated into clinical practice. Despite considerable efforts currently devoted to liver cancer research, only a few anti-HCC drugs are available, and patient prognosis and survival are still poor. The present paper provides a state-of-the-art overview of in vivo and in vitro models used for translational modeling of HCC with a specific focus on their key molecular hallmarks.

scholarly journals A Review on Chromatography—Mass Spectrometry Applications on Anthocyanin and Ellagitannin Metabolites of Blackberries and Raspberries

Foods ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2150
Author(s):  
Dilip K. Rai ◽  
Katerina Tzima
Keyword(s):  
Mass Spectrometry ◽  
Quantitative Analysis ◽  
Health Effects ◽  
Analytical Techniques ◽  
In Vitro Models ◽  
Qualitative And Quantitative Analysis ◽  
Qualitative And Quantitative ◽  
Chromatography Mass Spectrometry

Berries have been widely assessed for their beneficial health effects, predominately due to their high (poly)phenol content of anthocyanins and ellagitannins. After ellagitannins and ellagic acid are metabolized by the gut microbiome, a class of compounds known as urolithins are produced, which exert potential advantageous health effects. Anthocyanins, on the other hand, undergo a complex metabolic pathway after their interaction with microbial and endogenous enzymes, forming a broad range of metabolites and catabolic products. In most cases, in vitro models and cell lines are used to generate metabolites, whereas their assessment in vivo is currently limited. Thus far, several analytical methods have been developed for the qualitative and quantitative analysis of phenolic metabolites in berries, including liquid chromatography, mass spectrometry, and other hyphenated techniques, and have been undoubtedly valuable tools for the detailed metabolite characterization and profiling. In this review, a compilation of studies providing information on the qualitative and quantitative analysis of (poly)phenol metabolites in blackberries and raspberries after the utilization of in vitro and in vivo methods is presented. The different analytical techniques employed are assessed, focusing on the fate of the produced metabolic compounds in order to provide evidence on their characteristics, formation, and beneficial effects.

scholarly journals Evaluation of Novel Doxorubicin-Loaded Magnetic Wax Nanocomposite Vehicles as Cancer Combinatorial Therapy Agents

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 637
Author(s):  
Julia Jiménez-López ◽  
Lorena García-Hevia ◽  
Consolación Melguizo ◽  
Jose Prados ◽  
Manuel Bañobre-López ◽  
...  
Keyword(s):  
Preliminary Data ◽  
3D Models ◽  
In Vitro Models ◽  
Solid Tumours ◽  
Clinical Translation ◽  
Combinatorial Therapy ◽  
New Developments ◽  
In Vivo Tests

The development of nanotechnology-based solutions for cancer at a preclinical level advances at an astounding pace. So far, clinical translation of these new developments has not been able to keep the pace due to a range of different reasons. One of them is the mismatch between in vitro and in vivo results coming from the expected difference in complexity. To overcome this problem, extensive characterisation using advanced in vitro models can lead to stronger preliminary data to face in vivo tests. Here, a comprehensive in vitro validation of a combinatorial therapy nanoformulation against solid tumours is presented. The information extracted from the different in vitro models highlights the importance of advanced 3D models to fully understand the potential of this type of complex drugs.

scholarly journals Polysaccharides with Antitumor Effect in Breast Cancer: A Systematic Review of Non-Clinical Studies

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2008
Author(s):  
Claudia Rita Corso ◽  
Natalia Mulinari Turin de Oliveira ◽  
Leonardo Moura Cordeiro ◽  
Karien Sauruk da Silva ◽  
Suzany Hellen da Silva Soczek ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Cellular Proliferation ◽  
In Vitro Models ◽  
Mechanisms Of Action ◽  
Experimental Models ◽  
In Vivo Models ◽  
Apoptosis Inhibition

Purpose: To review the effects of polysaccharides and their proposed mechanisms of action in breast cancer experimental models. Data sources, selection, and extraction: Articles were selected by using PubMed, ScienceDirect, Scopus, and Medline, assessed from 1 May 2019 to 1 July 2020. The systematic review was registered in the International Prospective Register of Systematic Reviews (Prospero) under the number CRD42020169103. Results: Most of the studies explore algae polysaccharides (43.2%), followed by mushrooms (13.5%), plants (13.5%), fruits (10.8%), fungus (2.7%), bacteria, (2.7%), and sea animals (2.7%). A total of 8.1% investigated only in vitro models, 62.1% evaluated only in vivo models, and 29.7% evaluated in vitro and in vivo models. The mechanism of action involves apoptosis, inhibition of cellular proliferation, angiogenesis, and antimetastatic effects through multiple pathways. Conclusions: Findings included here support further investigations on the anti-tumor effect of polysaccharides. Some polysaccharides, such as fucoidan and β-glucans, deserve detailed and structured studies aiming at translational research on breast tumors, since they are already used in the clinical practice of other proposals of human health.

scholarly journals In Vitro Models for the Development of Peripheral Nerve Conduits, Part I: Design of a Fibrin Gel-Based Non-Contact Test

Polymers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 3573
Author(s):  
Paola De Stefano ◽  
Angelica Silvia Federici ◽  
Lorenza Draghi
Keyword(s):  
Peripheral Nerve ◽  
Clinical Performance ◽  
In Vitro Models ◽  
In Vitro Tests ◽  
Neural Cells ◽  
Animal Testing ◽  
Fibrin Gel ◽  
Specific Implementation

Current clinical strategies to repair peripheral nerve injuries draw on different approaches depending on the extent of lost tissue. Nerve guidance conduits (NGCs) are considered to be a promising, off-the-shelf alternative to autografts when modest gaps need to be repaired. Unfortunately, to date, the implantation of an NGC prevents the sacrifice of a healthy nerve at the price of suboptimal clinical performance. Despite the significant number of materials and fabrication strategies proposed, an ideal combination has not been yet identified. Validation and comparison of NGCs ultimately requires in vivo animal testing due to the lack of alternative models, but in the spirit of the 3R principles, a reliable in vitro model for preliminary screening is highly desirable. Nevertheless, more traditional in vitro tests, and direct cell seeding on the material in particular, are not representative of the actual regeneration scenario. Thus, we have designed a very simple set-up in the attempt to appreciate the relevant features of NGCs through in vitro testing, and we have verified its applicability using electrospun NGCs. To this aim, neural cells were encapsulated in a loose fibrin gel and enclosed within the NGC membrane. Different thicknesses and porosity values of two popular polymers (namely gelatin and polycaprolactone) were compared. Results indicate that, with specific implementation, the system might represent a useful tool to characterize crucial NGC design aspects.

scholarly journals Human skin explant model for the investigation of topical therapeutics

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jessica E. Neil ◽  
Marc B. Brown ◽  
Adrian C. Williams
Keyword(s):  
Human Skin ◽  
Ex Vivo ◽  
In Vitro Models ◽  
Animal Testing ◽  
Tissue Integrity ◽  
Human Illness ◽  
Cost Efficient ◽  
In Vivo Effects

AbstractThe development of in vitro and ex vivo models to mimic human illness is important not only for scientific understanding and investigating therapeutic approaches but also to mitigate animal testing and bridge the inter-species translational gap. While in vitro models can facilitate high-throughput and cost-efficient evaluation of novel therapeutics, more complex ex vivo systems can better predict both desirable and adverse in vivo effects. Here we describe an ex vivo cultured human skin explant model in which we have characterized pathological tissue integrity, barrier function and metabolic stability over time. Our findings suggest that human skin can be successfully cultured for pharmacodynamic use up to and beyond 9 days without any adverse physiological consequence.

Exploiting Anti-Inflammation Effects of Flavonoids in Chronic Inflammatory Diseases

2020 ◽  
Vol 26 (22) ◽  
pp. 2610-2619 ◽  
Author(s):  
Tarique Hussain ◽  
Ghulam Murtaza ◽  
Huansheng Yang ◽  
Muhammad S. Kalhoro ◽  
Dildar H. Kalhoro
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Cellular Level ◽  
Antiinflammatory Drugs ◽  
Suitable Alternative ◽  
Chronic Inflammatory Diseases

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

Modulation of Matrix Metalloproteinases by Plant-Derived Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Matrix Metalloproteinases ◽  
Animal Studies ◽  
Current Knowledge ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Extracellular Matrix Components

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

scholarly journals Human Saliva-Mediated Hydrolysis of Eugenyl-β-D-Glucoside and Fluorescein-di-β-D-Glucoside in In Vivo and In Vitro Models

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 172
Author(s):  
Mariusz Dziadas ◽  
Adam Junka ◽  
Henryk Jeleń
Keyword(s):  
Oral Cavity ◽  
Control Sample ◽  
Rapid Test ◽  
Human Saliva ◽  
In Vitro Models ◽  
Microbial Hydrolysis ◽  
Amoxicillin Trihydrate ◽  
Potassium Clavulanate

Eugenyl-β-D-glucopyranoside, also referred to as Citrusin C, is a natural glucoside found among others in cloves, basil and cinnamon plants. Eugenol in a form of free aglycone is used in perfumeries, flavourings, essential oils and in medicinal products. Synthetic Citrusin C was incubated with human saliva in several in vitro models together with substrate-specific enzyme and antibiotics (clindamycin, ciprofloxacin, amoxicillin trihydrate and potassium clavulanate). Citrusin C was detected using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Citrusin C was completely degraded only when incubated with substrate-specific A. niger glucosidase E.C 3.2.1.21 (control sample) and when incubated with human saliva (tested sample). The addition of antibiotics to the above-described experimental setting, stopped Citrusin C degradation, indicating microbiologic origin of hydrolysis observed. Our results demonstrate that Citrusin C is subjected to complete degradation by salivary/oral cavity microorganisms. Extrapolation of our results allows to state that in the human oral cavity, virtually all β-D-glucosides would follow this type of hydrolysis. Additionally, a new method was developed for an in vivo rapid test of glucosidase activity in the human mouth on the tongue using fluorescein-di-β-D-glucoside as substrate. The results presented in this study serve as a proof of concept for the hypothesis that microbial hydrolysis path of β-D-glucosides begins immediately in the human mouth and releases the aglycone directly into the gastrointestinal tract.

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