Exploring Galleria mellonella as a novel model for evaluating permeation and toxicity of natural compounds

Introduction Recent legislative advancements emphasize the need for alternative methods in assessing efficacy and safety while adhering to the 3Rs principles (reduce, replace, and refine) of animal experimentation. In this context, Galleria mellonella has become a well-established model in safety an...

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Main Authors: Samanta de Matos Silva, Junya de Lacorte Singulani, Lígia de Souza Fernandes, Ketylin Fernanda Migliato, Maria José Soares Mendes-Giannini, Ana Marisa Fusco-Almeida
Format: Article
Language:English
Published: European Publishing 2024-12-01
Series:Public Health and Toxicology
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Online Access:https://www.publichealthtoxicology.com/Exploring-Galleria-mellonella-as-a-novel-model-nfor-evaluating-permeation-and-toxicity,197414,0,2.html
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author Samanta de Matos Silva
Junya de Lacorte Singulani
Lígia de Souza Fernandes
Ketylin Fernanda Migliato
Maria José Soares Mendes-Giannini
Ana Marisa Fusco-Almeida
author_facet Samanta de Matos Silva
Junya de Lacorte Singulani
Lígia de Souza Fernandes
Ketylin Fernanda Migliato
Maria José Soares Mendes-Giannini
Ana Marisa Fusco-Almeida
author_sort Samanta de Matos Silva
collection DOAJ
description Introduction Recent legislative advancements emphasize the need for alternative methods in assessing efficacy and safety while adhering to the 3Rs principles (reduce, replace, and refine) of animal experimentation. In this context, Galleria mellonella has become a well-established model in safety and efficacy research. However, existing studies predominantly focus on its use in injectable routes concerning pathogens and chemical compounds, leaving a significant gap in understanding other administration pathways, particularly topical application. To address this gap and contribute to the validation of G. mellonella as a model for cutaneous absorption studies, our investigation compares the toxicity data of gallic acid (GA) in mammalian models, alternative animal models such as G. mellonella and Caenorhabditis elegans, as well as monolayer cell cultures, providing insights valuable for future research. Methods This was an experimental study aimed at evaluating the toxicity and permeation of gallic acid (GA) using different in vivo and in vitro alternative models, including G. mellonella, C. elegans, and monolayer cell cultures. Our study specifically evaluated the toxicity of GA in solution using human keratinocytes (HaCat), human dermal fibroblasts (HDFa), and human liver cell lines (HepG2), in addition to invertebrate animal models of C. elegans and semi-solid formulations in G. mellonella via topical administration. The results demonstrated GA’s higher toxicity in C. elegans, followed by sequential susceptibility in HaCat, HepG2, and HDFa cells. Results Surprisingly, G. mellonella displayed a notably high tolerance to GA, presenting no discernible alterations in cellular immune responses in injectable nor topical administration. Observations of the humoral immune response in G. mellonella larvae showcased melanization both administration conditions, indicating absorption following topical administration of higher GA concentrations. Conclusions GA demonstrated low toxicity in cellular models, whereas G. mellonella revealed promise as a methodology for topical toxicity testing in cutaneous absorption. However, further research is essential to validate its efficacy. These findings demonstrated the potential to establish correlations in toxicology data between various alternative methodologies and mammals, potentially aiding in the prediction of toxicity in humans.
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spelling doaj-art-b4839fc7d85e4ecd8a124cf69abc3e9a2025-08-20T01:49:40ZengEuropean PublishingPublic Health and Toxicology2732-89292024-12-01441910.18332/pht/197414197414Exploring Galleria mellonella as a novel model for evaluating permeation and toxicity of natural compoundsSamanta de Matos Silva0https://orcid.org/0000-0002-1390-117XJunya de Lacorte Singulani1Lígia de Souza Fernandes2Ketylin Fernanda Migliato3Maria José Soares Mendes-Giannini4Ana Marisa Fusco-Almeida5https://orcid.org/0000-0002-2115-8988São Paulo State University ‘Júlio de Mesquita Filho’ (UNESP), São Paulo, BrazilSão Paulo State University ‘Júlio de Mesquita Filho’ (UNESP), São Paulo, BrazilSão Paulo State University ‘Júlio de Mesquita Filho’ (UNESP), São Paulo, BrazilCentral Paulista University Center (UNICEP), São Paulo, BrazilSão Paulo State University ‘Júlio de Mesquita Filho’ (UNESP), São Paulo, BrazilSão Paulo State University ‘Júlio de Mesquita Filho’ (UNESP), São Paulo, BrazilIntroduction Recent legislative advancements emphasize the need for alternative methods in assessing efficacy and safety while adhering to the 3Rs principles (reduce, replace, and refine) of animal experimentation. In this context, Galleria mellonella has become a well-established model in safety and efficacy research. However, existing studies predominantly focus on its use in injectable routes concerning pathogens and chemical compounds, leaving a significant gap in understanding other administration pathways, particularly topical application. To address this gap and contribute to the validation of G. mellonella as a model for cutaneous absorption studies, our investigation compares the toxicity data of gallic acid (GA) in mammalian models, alternative animal models such as G. mellonella and Caenorhabditis elegans, as well as monolayer cell cultures, providing insights valuable for future research. Methods This was an experimental study aimed at evaluating the toxicity and permeation of gallic acid (GA) using different in vivo and in vitro alternative models, including G. mellonella, C. elegans, and monolayer cell cultures. Our study specifically evaluated the toxicity of GA in solution using human keratinocytes (HaCat), human dermal fibroblasts (HDFa), and human liver cell lines (HepG2), in addition to invertebrate animal models of C. elegans and semi-solid formulations in G. mellonella via topical administration. The results demonstrated GA’s higher toxicity in C. elegans, followed by sequential susceptibility in HaCat, HepG2, and HDFa cells. Results Surprisingly, G. mellonella displayed a notably high tolerance to GA, presenting no discernible alterations in cellular immune responses in injectable nor topical administration. Observations of the humoral immune response in G. mellonella larvae showcased melanization both administration conditions, indicating absorption following topical administration of higher GA concentrations. Conclusions GA demonstrated low toxicity in cellular models, whereas G. mellonella revealed promise as a methodology for topical toxicity testing in cutaneous absorption. However, further research is essential to validate its efficacy. These findings demonstrated the potential to establish correlations in toxicology data between various alternative methodologies and mammals, potentially aiding in the prediction of toxicity in humans.https://www.publichealthtoxicology.com/Exploring-Galleria-mellonella-as-a-novel-model-nfor-evaluating-permeation-and-toxicity,197414,0,2.htmltoxicitygallic acidgalleria mellonellacaenorhabditis eleganstopical administrationcells culture
spellingShingle Samanta de Matos Silva
Junya de Lacorte Singulani
Lígia de Souza Fernandes
Ketylin Fernanda Migliato
Maria José Soares Mendes-Giannini
Ana Marisa Fusco-Almeida
Exploring Galleria mellonella as a novel model for evaluating permeation and toxicity of natural compounds
Public Health and Toxicology
toxicity
gallic acid
galleria mellonella
caenorhabditis elegans
topical administration
cells culture
title Exploring Galleria mellonella as a novel model for evaluating permeation and toxicity of natural compounds
title_full Exploring Galleria mellonella as a novel model for evaluating permeation and toxicity of natural compounds
title_fullStr Exploring Galleria mellonella as a novel model for evaluating permeation and toxicity of natural compounds
title_full_unstemmed Exploring Galleria mellonella as a novel model for evaluating permeation and toxicity of natural compounds
title_short Exploring Galleria mellonella as a novel model for evaluating permeation and toxicity of natural compounds
title_sort exploring galleria mellonella as a novel model for evaluating permeation and toxicity of natural compounds
topic toxicity
gallic acid
galleria mellonella
caenorhabditis elegans
topical administration
cells culture
url https://www.publichealthtoxicology.com/Exploring-Galleria-mellonella-as-a-novel-model-nfor-evaluating-permeation-and-toxicity,197414,0,2.html
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