Safety evaluation of ondansetron after gestational exposure on male reproductive parameters in rats
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , |
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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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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1808129395986006016 |