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Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar rats

Bibliographic Details
Main Author: Fiais, Gabriela Alice [UNESP]
Publication Date: 2023
Other Authors: Ferreira, Douglas Sadrac de Biagi [UNESP], de Freitas, Rayara Nogueira [UNESP], da Silva, Lucas Guilherme Leite [UNESP], Kawaguchi, Marcelo [UNESP], Veras, Allice Santos Cruz [UNESP], Teixeira, Giovana Rampazzo [UNESP], Antoniali, Cristina [UNESP], Dornelles, Rita Cássia Menegati [UNESP], Nakamune, Ana Cláudia de Melo Stevanato [UNESP], Fakhouri, Walid D., Chaves-Neto, Antonio Hernandes [UNESP]
Format: Article
Language: eng
Source: Repositório Institucional da UNESP
Download full: http://dx.doi.org/10.1016/j.tox.2023.153615
https://hdl.handle.net/11449/306449
Summary: Levetiracetam (LEV) is an anticonvulsant for epilepsy. The toxic effects of this medication in tissues have been associated with redox state imbalance, which can lead to salivary gland dysfunction. Therefore, the current work investigated the effects of LEV on the biochemical, functional, and redox parameters of the parotid and submandibular glands in rats. For this, male Wistar rats (Rattus norvegicus albinus) were randomly divided into 3 groups (n = 10/group): Control (0.9% saline solution), LEV100 (100 mg/kg), and LEV300 (300 mg/kg). After 21 consecutive days of intragastric gavage treatments, pilocarpine stimulated saliva secretion was collected for salivary biochemical analysis. The extracted salivary glands were utilized for histomorphometry and redox state analyses. Our results showed that LEV300 increased plasma hepatotoxicity markers and reduced salivary amylase activity and the acinar surface area of the parotid gland. Total oxidant capacity and oxidative damage to lipids and proteins were higher in the parotid gland, while total antioxidant capacity and uric acid levels were reduced in the submandibular gland of the LEV100 group compared to Control. On the other hand, total oxidant capacity, oxidative damage to lipids and proteins, total antioxidant capacity, and uric acid levels were lower in both salivary glands of the LEV300 group compared to Control. Superoxide dismutase and glutathione peroxidase activities were lower in the salivary glands of treated animals compared to Control. In conclusion our data suggest that treatment with LEV represents a potentially toxic agent, that contributes to drug-induced salivary gland dysfunction.
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spelling Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar ratsAnticonvulsantEpilepsy medication, LevetiracetamOxidative stressSalivaSalivary glandsLevetiracetam (LEV) is an anticonvulsant for epilepsy. The toxic effects of this medication in tissues have been associated with redox state imbalance, which can lead to salivary gland dysfunction. Therefore, the current work investigated the effects of LEV on the biochemical, functional, and redox parameters of the parotid and submandibular glands in rats. For this, male Wistar rats (Rattus norvegicus albinus) were randomly divided into 3 groups (n = 10/group): Control (0.9% saline solution), LEV100 (100 mg/kg), and LEV300 (300 mg/kg). After 21 consecutive days of intragastric gavage treatments, pilocarpine stimulated saliva secretion was collected for salivary biochemical analysis. The extracted salivary glands were utilized for histomorphometry and redox state analyses. Our results showed that LEV300 increased plasma hepatotoxicity markers and reduced salivary amylase activity and the acinar surface area of the parotid gland. Total oxidant capacity and oxidative damage to lipids and proteins were higher in the parotid gland, while total antioxidant capacity and uric acid levels were reduced in the submandibular gland of the LEV100 group compared to Control. On the other hand, total oxidant capacity, oxidative damage to lipids and proteins, total antioxidant capacity, and uric acid levels were lower in both salivary glands of the LEV300 group compared to Control. Superoxide dismutase and glutathione peroxidase activities were lower in the salivary glands of treated animals compared to Control. In conclusion our data suggest that treatment with LEV represents a potentially toxic agent, that contributes to drug-induced salivary gland dysfunction.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Departmento de Ciências Básicas Universidade Estadual Paulista (Unesp) Faculdade de Odontologia, São PauloDepartamento de Educação Física Universidade Estadual Paulista (Unesp), São PauloPrograma de Pós-Graduação em Ciência Odontológica - Saúde Bucal da Criança Universidade Estadual Paulista (Unesp) Faculdade de Odontologia, São PauloPrograma de Pós-Graduação Multicêntrico em Ciências Fisiológicas SBFis Universidade Estadual Paulista (Unesp) Faculdade de Odontologia, São PauloCenter for Craniofacial Research Department of Diagnostic and Biomedical Sciences School of Dentistry University of Texas Health Science Center at HoustonDepartmento de Ciências Básicas Universidade Estadual Paulista (Unesp) Faculdade de Odontologia, São PauloDepartamento de Educação Física Universidade Estadual Paulista (Unesp), São PauloPrograma de Pós-Graduação em Ciência Odontológica - Saúde Bucal da Criança Universidade Estadual Paulista (Unesp) Faculdade de Odontologia, São PauloPrograma de Pós-Graduação Multicêntrico em Ciências Fisiológicas SBFis Universidade Estadual Paulista (Unesp) Faculdade de Odontologia, São PauloCAPES: 001FAPESP: 2021/10604–7Universidade Estadual Paulista (UNESP)University of Texas Health Science Center at HoustonFiais, Gabriela Alice [UNESP]Ferreira, Douglas Sadrac de Biagi [UNESP]de Freitas, Rayara Nogueira [UNESP]da Silva, Lucas Guilherme Leite [UNESP]Kawaguchi, Marcelo [UNESP]Veras, Allice Santos Cruz [UNESP]Teixeira, Giovana Rampazzo [UNESP]Antoniali, Cristina [UNESP]Dornelles, Rita Cássia Menegati [UNESP]Nakamune, Ana Cláudia de Melo Stevanato [UNESP]Fakhouri, Walid D.Chaves-Neto, Antonio Hernandes [UNESP]2025-04-29T20:06:17Z2023-09-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.tox.2023.153615Toxicology, v. 496.1879-31850300-483Xhttps://hdl.handle.net/11449/30644910.1016/j.tox.2023.1536152-s2.0-85168447975Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengToxicologyinfo:eu-repo/semantics/openAccess2025-04-30T13:54:55Zoai:repositorio.unesp.br:11449/306449Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462025-04-30T13:54:55Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar rats
title Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar rats
spellingShingle Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar rats
Fiais, Gabriela Alice [UNESP]
Anticonvulsant
Epilepsy medication, Levetiracetam
Oxidative stress
Saliva
Salivary glands
title_short Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar rats
title_full Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar rats
title_fullStr Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar rats
title_full_unstemmed Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar rats
title_sort Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar rats
author Fiais, Gabriela Alice [UNESP]
author_facet Fiais, Gabriela Alice [UNESP]
Ferreira, Douglas Sadrac de Biagi [UNESP]
de Freitas, Rayara Nogueira [UNESP]
da Silva, Lucas Guilherme Leite [UNESP]
Kawaguchi, Marcelo [UNESP]
Veras, Allice Santos Cruz [UNESP]
Teixeira, Giovana Rampazzo [UNESP]
Antoniali, Cristina [UNESP]
Dornelles, Rita Cássia Menegati [UNESP]
Nakamune, Ana Cláudia de Melo Stevanato [UNESP]
Fakhouri, Walid D.
Chaves-Neto, Antonio Hernandes [UNESP]
author_role author
author2 Ferreira, Douglas Sadrac de Biagi [UNESP]
de Freitas, Rayara Nogueira [UNESP]
da Silva, Lucas Guilherme Leite [UNESP]
Kawaguchi, Marcelo [UNESP]
Veras, Allice Santos Cruz [UNESP]
Teixeira, Giovana Rampazzo [UNESP]
Antoniali, Cristina [UNESP]
Dornelles, Rita Cássia Menegati [UNESP]
Nakamune, Ana Cláudia de Melo Stevanato [UNESP]
Fakhouri, Walid D.
Chaves-Neto, Antonio Hernandes [UNESP]
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
University of Texas Health Science Center at Houston
dc.contributor.author.fl_str_mv Fiais, Gabriela Alice [UNESP]
Ferreira, Douglas Sadrac de Biagi [UNESP]
de Freitas, Rayara Nogueira [UNESP]
da Silva, Lucas Guilherme Leite [UNESP]
Kawaguchi, Marcelo [UNESP]
Veras, Allice Santos Cruz [UNESP]
Teixeira, Giovana Rampazzo [UNESP]
Antoniali, Cristina [UNESP]
Dornelles, Rita Cássia Menegati [UNESP]
Nakamune, Ana Cláudia de Melo Stevanato [UNESP]
Fakhouri, Walid D.
Chaves-Neto, Antonio Hernandes [UNESP]
dc.subject.por.fl_str_mv Anticonvulsant
Epilepsy medication, Levetiracetam
Oxidative stress
Saliva
Salivary glands
topic Anticonvulsant
Epilepsy medication, Levetiracetam
Oxidative stress
Saliva
Salivary glands
description Levetiracetam (LEV) is an anticonvulsant for epilepsy. The toxic effects of this medication in tissues have been associated with redox state imbalance, which can lead to salivary gland dysfunction. Therefore, the current work investigated the effects of LEV on the biochemical, functional, and redox parameters of the parotid and submandibular glands in rats. For this, male Wistar rats (Rattus norvegicus albinus) were randomly divided into 3 groups (n = 10/group): Control (0.9% saline solution), LEV100 (100 mg/kg), and LEV300 (300 mg/kg). After 21 consecutive days of intragastric gavage treatments, pilocarpine stimulated saliva secretion was collected for salivary biochemical analysis. The extracted salivary glands were utilized for histomorphometry and redox state analyses. Our results showed that LEV300 increased plasma hepatotoxicity markers and reduced salivary amylase activity and the acinar surface area of the parotid gland. Total oxidant capacity and oxidative damage to lipids and proteins were higher in the parotid gland, while total antioxidant capacity and uric acid levels were reduced in the submandibular gland of the LEV100 group compared to Control. On the other hand, total oxidant capacity, oxidative damage to lipids and proteins, total antioxidant capacity, and uric acid levels were lower in both salivary glands of the LEV300 group compared to Control. Superoxide dismutase and glutathione peroxidase activities were lower in the salivary glands of treated animals compared to Control. In conclusion our data suggest that treatment with LEV represents a potentially toxic agent, that contributes to drug-induced salivary gland dysfunction.
publishDate 2023
dc.date.none.fl_str_mv 2023-09-01
2025-04-29T20:06:17Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.tox.2023.153615
Toxicology, v. 496.
1879-3185
0300-483X
https://hdl.handle.net/11449/306449
10.1016/j.tox.2023.153615
2-s2.0-85168447975
url http://dx.doi.org/10.1016/j.tox.2023.153615
https://hdl.handle.net/11449/306449
identifier_str_mv Toxicology, v. 496.
1879-3185
0300-483X
10.1016/j.tox.2023.153615
2-s2.0-85168447975
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Toxicology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv repositoriounesp@unesp.br
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