Safety evaluation of ondansetron after gestational exposure on male reproductive parameters in rats

Detalhes bibliográficos
Autor(a) principal: Reis, Ana Carolina Casali [UNESP]
Data de Publicação: 2023
Outros Autores: Jorge, Bárbara Campos [UNESP], Stein, Julia [UNESP], Moreira, Suyane da Silva [UNESP], Manoel, Beatriz de Matos [UNESP], Aquino, Ariana Musa [UNESP], Valente, Leticia Cardoso, Kassuya, Cândida Aparecida Leite, Scarano, Wellerson Rodrigo [UNESP], Arena, Arielle Cristina [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.yrtph.2022.105302
http://hdl.handle.net/11449/248072
Resumo: Ondansetron is a 5HT3 receptor antagonist widely used to treat hyperemesis gravidarum, although its safety is still questionable. Since 5HT3 receptors, which are the target of this drug, can interfere with brain development through changes in neurotransmitter levels, this study evaluated whether the prenatal exposure to this drug could compromise reproductive and behavioral parameters in male offspring. Pregnant rats were treated with ondansetron (1.7 and 2.5 mg/kg/body weight; gavage), from gestational day 1–21. No exposure-related changes in clinical signs, body weight, food consumption, pregnancy length, and necropsy findings were observed in dams. Ondansetron exposure did not alter the anogenital distance or age of preputial separation in male offspring. Similarly, males exposed to therapeutic doses of ondansetron did not exhibit changes in play behavior. In adulthood, there were no changes in sperm parameters, as well as in testosterone level, sexual behavior and fertility. Furthermore, ondansetron did not interfere with testicular and epididymal histology, and with androgen receptor expression in hypothalamus. In conclusion, prenatal exposure to ondansetron did not cause maternal toxicity, as well as did not interfere with reproductive parameters of male offspring, indicating its safety after gestational exposure in rats.
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spelling Safety evaluation of ondansetron after gestational exposure on male reproductive parameters in rats5HT3Brain sexual differentiationHyperemesis gravidarumMale ratsPregnancyOndansetron is a 5HT3 receptor antagonist widely used to treat hyperemesis gravidarum, although its safety is still questionable. Since 5HT3 receptors, which are the target of this drug, can interfere with brain development through changes in neurotransmitter levels, this study evaluated whether the prenatal exposure to this drug could compromise reproductive and behavioral parameters in male offspring. Pregnant rats were treated with ondansetron (1.7 and 2.5 mg/kg/body weight; gavage), from gestational day 1–21. No exposure-related changes in clinical signs, body weight, food consumption, pregnancy length, and necropsy findings were observed in dams. Ondansetron exposure did not alter the anogenital distance or age of preputial separation in male offspring. Similarly, males exposed to therapeutic doses of ondansetron did not exhibit changes in play behavior. In adulthood, there were no changes in sperm parameters, as well as in testosterone level, sexual behavior and fertility. Furthermore, ondansetron did not interfere with testicular and epididymal histology, and with androgen receptor expression in hypothalamus. In conclusion, prenatal exposure to ondansetron did not cause maternal toxicity, as well as did not interfere with reproductive parameters of male offspring, indicating its safety after gestational exposure in rats.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Institute of Biosciences of Botucatu Department of Structural and Functional Biology University. Estadual Paulista – Botucatu (UNESP), São PauloSchool of Health Sciences Federal University of Grande Dourados (UFGD), MSCenter of Toxicological Assistance (CEATOX) Institute of Biosciences of Botucatu Univ. Estadual Paulista – Botucatu (UNESP), São Paulo StateInstitute of Biosciences of Botucatu Department of Structural and Functional Biology University. Estadual Paulista – Botucatu (UNESP), São PauloCenter of Toxicological Assistance (CEATOX) Institute of Biosciences of Botucatu Univ. Estadual Paulista – Botucatu (UNESP), São Paulo StateFAPESP: 2020/08745–9Universidade Estadual Paulista (UNESP)Federal University of Grande Dourados (UFGD)Reis, Ana Carolina Casali [UNESP]Jorge, Bárbara Campos [UNESP]Stein, Julia [UNESP]Moreira, Suyane da Silva [UNESP]Manoel, Beatriz de Matos [UNESP]Aquino, Ariana Musa [UNESP]Valente, Leticia CardosoKassuya, Cândida Aparecida LeiteScarano, Wellerson Rodrigo [UNESP]Arena, Arielle Cristina [UNESP]2023-07-29T13:33:41Z2023-07-29T13:33:41Z2023-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.yrtph.2022.105302Regulatory Toxicology and Pharmacology, v. 137.1096-02950273-2300http://hdl.handle.net/11449/24807210.1016/j.yrtph.2022.1053022-s2.0-85144589855Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengRegulatory Toxicology and Pharmacologyinfo:eu-repo/semantics/openAccess2024-04-10T18:10:59Zoai:repositorio.unesp.br:11449/248072Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:08:07.563659Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Safety evaluation of ondansetron after gestational exposure on male reproductive parameters in rats
title Safety evaluation of ondansetron after gestational exposure on male reproductive parameters in rats
spellingShingle Safety evaluation of ondansetron after gestational exposure on male reproductive parameters in rats
Reis, Ana Carolina Casali [UNESP]
5HT3
Brain sexual differentiation
Hyperemesis gravidarum
Male rats
Pregnancy
title_short Safety evaluation of ondansetron after gestational exposure on male reproductive parameters in rats
title_full Safety evaluation of ondansetron after gestational exposure on male reproductive parameters in rats
title_fullStr Safety evaluation of ondansetron after gestational exposure on male reproductive parameters in rats
title_full_unstemmed Safety evaluation of ondansetron after gestational exposure on male reproductive parameters in rats
title_sort Safety evaluation of ondansetron after gestational exposure on male reproductive parameters in rats
author Reis, Ana Carolina Casali [UNESP]
author_facet Reis, Ana Carolina Casali [UNESP]
Jorge, Bárbara Campos [UNESP]
Stein, Julia [UNESP]
Moreira, Suyane da Silva [UNESP]
Manoel, Beatriz de Matos [UNESP]
Aquino, Ariana Musa [UNESP]
Valente, Leticia Cardoso
Kassuya, Cândida Aparecida Leite
Scarano, Wellerson Rodrigo [UNESP]
Arena, Arielle Cristina [UNESP]
author_role author
author2 Jorge, Bárbara Campos [UNESP]
Stein, Julia [UNESP]
Moreira, Suyane da Silva [UNESP]
Manoel, Beatriz de Matos [UNESP]
Aquino, Ariana Musa [UNESP]
Valente, Leticia Cardoso
Kassuya, Cândida Aparecida Leite
Scarano, Wellerson Rodrigo [UNESP]
Arena, Arielle Cristina [UNESP]
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
Federal University of Grande Dourados (UFGD)
dc.contributor.author.fl_str_mv Reis, Ana Carolina Casali [UNESP]
Jorge, Bárbara Campos [UNESP]
Stein, Julia [UNESP]
Moreira, Suyane da Silva [UNESP]
Manoel, Beatriz de Matos [UNESP]
Aquino, Ariana Musa [UNESP]
Valente, Leticia Cardoso
Kassuya, Cândida Aparecida Leite
Scarano, Wellerson Rodrigo [UNESP]
Arena, Arielle Cristina [UNESP]
dc.subject.por.fl_str_mv 5HT3
Brain sexual differentiation
Hyperemesis gravidarum
Male rats
Pregnancy
topic 5HT3
Brain sexual differentiation
Hyperemesis gravidarum
Male rats
Pregnancy
description Ondansetron is a 5HT3 receptor antagonist widely used to treat hyperemesis gravidarum, although its safety is still questionable. Since 5HT3 receptors, which are the target of this drug, can interfere with brain development through changes in neurotransmitter levels, this study evaluated whether the prenatal exposure to this drug could compromise reproductive and behavioral parameters in male offspring. Pregnant rats were treated with ondansetron (1.7 and 2.5 mg/kg/body weight; gavage), from gestational day 1–21. No exposure-related changes in clinical signs, body weight, food consumption, pregnancy length, and necropsy findings were observed in dams. Ondansetron exposure did not alter the anogenital distance or age of preputial separation in male offspring. Similarly, males exposed to therapeutic doses of ondansetron did not exhibit changes in play behavior. In adulthood, there were no changes in sperm parameters, as well as in testosterone level, sexual behavior and fertility. Furthermore, ondansetron did not interfere with testicular and epididymal histology, and with androgen receptor expression in hypothalamus. In conclusion, prenatal exposure to ondansetron did not cause maternal toxicity, as well as did not interfere with reproductive parameters of male offspring, indicating its safety after gestational exposure in rats.
publishDate 2023
dc.date.none.fl_str_mv 2023-07-29T13:33:41Z
2023-07-29T13:33:41Z
2023-01-01
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.yrtph.2022.105302
Regulatory Toxicology and Pharmacology, v. 137.
1096-0295
0273-2300
http://hdl.handle.net/11449/248072
10.1016/j.yrtph.2022.105302
2-s2.0-85144589855
url http://dx.doi.org/10.1016/j.yrtph.2022.105302
http://hdl.handle.net/11449/248072
identifier_str_mv Regulatory Toxicology and Pharmacology, v. 137.
1096-0295
0273-2300
10.1016/j.yrtph.2022.105302
2-s2.0-85144589855
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Regulatory Toxicology and Pharmacology
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
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