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Tenebrio molitor as a Simple and Cheap Preclinical Pharmacokinetic and Toxicity Model

The progression of drugs into clinical phases requires proper toxicity assessment in animals and the correct identification of possible metabolites. Accordingly, different animal models are used to preliminarily evaluate toxicity and biotransformations. Rodents are the most common models used to pre...

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Autores principales: Brai, Annalaura, Poggialini, Federica, Vagaggini, Chiara, Pasqualini, Claudia, Simoni, Sauro, Francardi, Valeria, Dreassi, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917132/
https://www.ncbi.nlm.nih.gov/pubmed/36768618
http://dx.doi.org/10.3390/ijms24032296
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author Brai, Annalaura
Poggialini, Federica
Vagaggini, Chiara
Pasqualini, Claudia
Simoni, Sauro
Francardi, Valeria
Dreassi, Elena
author_facet Brai, Annalaura
Poggialini, Federica
Vagaggini, Chiara
Pasqualini, Claudia
Simoni, Sauro
Francardi, Valeria
Dreassi, Elena
author_sort Brai, Annalaura
collection PubMed
description The progression of drugs into clinical phases requires proper toxicity assessment in animals and the correct identification of possible metabolites. Accordingly, different animal models are used to preliminarily evaluate toxicity and biotransformations. Rodents are the most common models used to preliminarily evaluate the safety of drugs; however, their use is subject to ethical consideration and elevated costs, and strictly regulated by national legislations. Herein, we developed a novel, cheap and convenient toxicity model using Tenebrio molitor coleoptera (TMC). A panel of 15 drugs—including antivirals and antibacterials—with different therapeutic applications was administered to TMC and the LD50 was determined. The values are comparable with those already determined in mice and rats. In addition, a TMC model was used to determine the presence of the main metabolites and in vivo pharmacokinetics (PK), and results were compared with those available from in vitro assays and the literature. Taken together, our results demonstrate that TMC can be used as a novel and convenient preliminary toxicity model to preliminarily evaluate the safety of experimental compounds and the formation of main metabolites, and to reduce the costs and number of rodents, according to 3R principles.
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spelling pubmed-99171322023-02-11 Tenebrio molitor as a Simple and Cheap Preclinical Pharmacokinetic and Toxicity Model Brai, Annalaura Poggialini, Federica Vagaggini, Chiara Pasqualini, Claudia Simoni, Sauro Francardi, Valeria Dreassi, Elena Int J Mol Sci Article The progression of drugs into clinical phases requires proper toxicity assessment in animals and the correct identification of possible metabolites. Accordingly, different animal models are used to preliminarily evaluate toxicity and biotransformations. Rodents are the most common models used to preliminarily evaluate the safety of drugs; however, their use is subject to ethical consideration and elevated costs, and strictly regulated by national legislations. Herein, we developed a novel, cheap and convenient toxicity model using Tenebrio molitor coleoptera (TMC). A panel of 15 drugs—including antivirals and antibacterials—with different therapeutic applications was administered to TMC and the LD50 was determined. The values are comparable with those already determined in mice and rats. In addition, a TMC model was used to determine the presence of the main metabolites and in vivo pharmacokinetics (PK), and results were compared with those available from in vitro assays and the literature. Taken together, our results demonstrate that TMC can be used as a novel and convenient preliminary toxicity model to preliminarily evaluate the safety of experimental compounds and the formation of main metabolites, and to reduce the costs and number of rodents, according to 3R principles. MDPI 2023-01-24 /pmc/articles/PMC9917132/ /pubmed/36768618 http://dx.doi.org/10.3390/ijms24032296 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brai, Annalaura
Poggialini, Federica
Vagaggini, Chiara
Pasqualini, Claudia
Simoni, Sauro
Francardi, Valeria
Dreassi, Elena
Tenebrio molitor as a Simple and Cheap Preclinical Pharmacokinetic and Toxicity Model
title Tenebrio molitor as a Simple and Cheap Preclinical Pharmacokinetic and Toxicity Model
title_full Tenebrio molitor as a Simple and Cheap Preclinical Pharmacokinetic and Toxicity Model
title_fullStr Tenebrio molitor as a Simple and Cheap Preclinical Pharmacokinetic and Toxicity Model
title_full_unstemmed Tenebrio molitor as a Simple and Cheap Preclinical Pharmacokinetic and Toxicity Model
title_short Tenebrio molitor as a Simple and Cheap Preclinical Pharmacokinetic and Toxicity Model
title_sort tenebrio molitor as a simple and cheap preclinical pharmacokinetic and toxicity model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917132/
https://www.ncbi.nlm.nih.gov/pubmed/36768618
http://dx.doi.org/10.3390/ijms24032296
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