In Vitro and Predictive Computational Toxicology Methods for the Neurotoxic Pesticide Amitraz and Its Metabolites
The <i>Varroa destructor</i> parasite is responsible for varroasis in honeybees worldwide, the most destructive disease among parasitic diseases. Thus, different insecticides/acaricides have been widely used within beehives to control these parasitic diseases. Namely, amitraz is the most...
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MDPI AG
2023-02-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/13/2/252 |
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| author | Marialuce Giorgini Mercedes Taroncher María-José Ruiz Yelko Rodríguez-Carrasco Josefa Tolosa |
| author_facet | Marialuce Giorgini Mercedes Taroncher María-José Ruiz Yelko Rodríguez-Carrasco Josefa Tolosa |
| author_sort | Marialuce Giorgini |
| collection | DOAJ |
| description | The <i>Varroa destructor</i> parasite is responsible for varroasis in honeybees worldwide, the most destructive disease among parasitic diseases. Thus, different insecticides/acaricides have been widely used within beehives to control these parasitic diseases. Namely, amitraz is the most used acaricide due to its high efficacy shown against <i>Varroa destructor</i>. However, pesticides used for beehive treatments could be incorporated into the honey and accumulate in other hive products. Hence, honeybee health and the impairment of the quality of honey caused by pesticides have gained more attention. Amitraz and its main metabolites, N-(2,4-dimethylphenyl) formamide (2,4-DMF) and 2,4-dimethylaniline (2,4-DMA), are known to be potent neurotoxicants. In this research, the cytotoxicity of amitraz and its metabolites has been assessed by MTT and PC assays in HepG2 cells. In addition, possible target receptors by in silico strategies have been surveyed. Results showed that amitraz was more cytotoxic than its metabolites. According to the in silico ADMEt assays, amitraz and its metabolites were predicted to be compounds that are able to pass the blood–brain barrier (BBB) and induce toxicity in the central and peripheral nervous systems. The main target class predicted for amitraz was the family of A G protein-coupled receptors that comprises responses to hormones and neurotransmitters. This affects, among other things, reproduction, development, locomotion, and feeding. Furthermore, amitraz and its metabolites were predicted as active compounds interacting with diverse receptors of the Tox21-nuclear receptor signaling and stress response pathways. |
| first_indexed | 2024-03-11T09:05:06Z |
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| language | English |
| last_indexed | 2024-03-11T09:05:06Z |
| publishDate | 2023-02-01 |
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| series | Brain Sciences |
| spelling | doaj.art-86ea56cd2a8f44d696c501788fde7f3e2023-11-16T19:28:23ZengMDPI AGBrain Sciences2076-34252023-02-0113225210.3390/brainsci13020252In Vitro and Predictive Computational Toxicology Methods for the Neurotoxic Pesticide Amitraz and Its MetabolitesMarialuce Giorgini0Mercedes Taroncher1María-José Ruiz2Yelko Rodríguez-Carrasco3Josefa Tolosa4Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, SpainLaboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, SpainLaboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, SpainLaboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, SpainLaboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, SpainThe <i>Varroa destructor</i> parasite is responsible for varroasis in honeybees worldwide, the most destructive disease among parasitic diseases. Thus, different insecticides/acaricides have been widely used within beehives to control these parasitic diseases. Namely, amitraz is the most used acaricide due to its high efficacy shown against <i>Varroa destructor</i>. However, pesticides used for beehive treatments could be incorporated into the honey and accumulate in other hive products. Hence, honeybee health and the impairment of the quality of honey caused by pesticides have gained more attention. Amitraz and its main metabolites, N-(2,4-dimethylphenyl) formamide (2,4-DMF) and 2,4-dimethylaniline (2,4-DMA), are known to be potent neurotoxicants. In this research, the cytotoxicity of amitraz and its metabolites has been assessed by MTT and PC assays in HepG2 cells. In addition, possible target receptors by in silico strategies have been surveyed. Results showed that amitraz was more cytotoxic than its metabolites. According to the in silico ADMEt assays, amitraz and its metabolites were predicted to be compounds that are able to pass the blood–brain barrier (BBB) and induce toxicity in the central and peripheral nervous systems. The main target class predicted for amitraz was the family of A G protein-coupled receptors that comprises responses to hormones and neurotransmitters. This affects, among other things, reproduction, development, locomotion, and feeding. Furthermore, amitraz and its metabolites were predicted as active compounds interacting with diverse receptors of the Tox21-nuclear receptor signaling and stress response pathways.https://www.mdpi.com/2076-3425/13/2/252neurotoxicitycytotoxicityin silico methodsamitrazmetabolites |
| spellingShingle | Marialuce Giorgini Mercedes Taroncher María-José Ruiz Yelko Rodríguez-Carrasco Josefa Tolosa In Vitro and Predictive Computational Toxicology Methods for the Neurotoxic Pesticide Amitraz and Its Metabolites Brain Sciences neurotoxicity cytotoxicity in silico methods amitraz metabolites |
| title | In Vitro and Predictive Computational Toxicology Methods for the Neurotoxic Pesticide Amitraz and Its Metabolites |
| title_full | In Vitro and Predictive Computational Toxicology Methods for the Neurotoxic Pesticide Amitraz and Its Metabolites |
| title_fullStr | In Vitro and Predictive Computational Toxicology Methods for the Neurotoxic Pesticide Amitraz and Its Metabolites |
| title_full_unstemmed | In Vitro and Predictive Computational Toxicology Methods for the Neurotoxic Pesticide Amitraz and Its Metabolites |
| title_short | In Vitro and Predictive Computational Toxicology Methods for the Neurotoxic Pesticide Amitraz and Its Metabolites |
| title_sort | in vitro and predictive computational toxicology methods for the neurotoxic pesticide amitraz and its metabolites |
| topic | neurotoxicity cytotoxicity in silico methods amitraz metabolites |
| url | https://www.mdpi.com/2076-3425/13/2/252 |
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