Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1002/jat.3955 http://hdl.handle.net/11449/201568 |
Resumo: | Many obese patients are exposed to hypolipidemic and serotonin-norepinephrine reuptake inhibitor (SNRI) drugs. Statins are one of the most marketed drugs in the world to treat dyslipidemia, while sibutramine, a SNRI drug, is prescribed in some countries to treat obesity and is detected as an additive in many adulterated weight loss supplements marketed worldwide. Previous studies reported adverse effects of isolated exposure to these drugs on male rat reproductive parameters. In the present work, we further investigated male reproductive toxicity of these drugs, administered in isolation or combination in adult rats for a longer period of treatment. Adult male rats (90 days) were treated (gavage) for 70 days with saline and dimethyl sulfoxide (control), sibutramine (10 mg/kg), rosuvastatin (5 mg/kg), or rosuvastatin combined with sibutramine. Sibutramine alone or with rosuvastatin, promoted a reduction in food intake and body weight gain, weight of the epididymis, ventral prostate and seminal vesicle; as well as decreased sperm reserves and transit time through the epididymis; androgen depletion; and increased index of cytoplasmic droplet. The rosuvastatin-treated group showed reduced frequency of ejaculation. Exposure to this drug alone or combined with sibutramine impaired epididymal morphology. Co-exposed rats had altered epididymal morphometry, and seminal vesicle and testis weights. The rats also showed decreased fertility after natural mating and a trend toward a delay in ejaculation, suggesting a small synergistic effect of these drugs. Given the greater reproductive efficiency of rodents, the results obtained in the present study raise concern regarding possible fertility impairment in men taking statins and SNRI drugs. |
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Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male ratsfertilitymale ratreproductive toxicityrosuvastatinsibutramineMany obese patients are exposed to hypolipidemic and serotonin-norepinephrine reuptake inhibitor (SNRI) drugs. Statins are one of the most marketed drugs in the world to treat dyslipidemia, while sibutramine, a SNRI drug, is prescribed in some countries to treat obesity and is detected as an additive in many adulterated weight loss supplements marketed worldwide. Previous studies reported adverse effects of isolated exposure to these drugs on male rat reproductive parameters. In the present work, we further investigated male reproductive toxicity of these drugs, administered in isolation or combination in adult rats for a longer period of treatment. Adult male rats (90 days) were treated (gavage) for 70 days with saline and dimethyl sulfoxide (control), sibutramine (10 mg/kg), rosuvastatin (5 mg/kg), or rosuvastatin combined with sibutramine. Sibutramine alone or with rosuvastatin, promoted a reduction in food intake and body weight gain, weight of the epididymis, ventral prostate and seminal vesicle; as well as decreased sperm reserves and transit time through the epididymis; androgen depletion; and increased index of cytoplasmic droplet. The rosuvastatin-treated group showed reduced frequency of ejaculation. Exposure to this drug alone or combined with sibutramine impaired epididymal morphology. Co-exposed rats had altered epididymal morphometry, and seminal vesicle and testis weights. The rats also showed decreased fertility after natural mating and a trend toward a delay in ejaculation, suggesting a small synergistic effect of these drugs. Given the greater reproductive efficiency of rodents, the results obtained in the present study raise concern regarding possible fertility impairment in men taking statins and SNRI drugs.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Morphology Institute of Biosciences São Paulo State University - UNESPGraduate Program in Cell and Structural Biology Institute of Biology State University of Campinas – UNICAMPDepartment of Morphology Physiology and Basic Pathology School of Dentistry of Ribeirão Preto University of São Paulo – USPReproductive Toxicity Branch Toxicity Assessment Division National Health and Environmental Effects Research Laboratory Office of Research and Development US Environmental Protection AgencyDepartment of Morphology Institute of Biosciences São Paulo State University - UNESPFAPESP: 2014/15566-2CNPq: 308842/2013-8CNPq: 312118/2017-1Universidade Estadual Paulista (Unesp)Universidade Estadual de Campinas (UNICAMP)Universidade de São Paulo (USP)US Environmental Protection Agencye Silva, Patrícia Villela [UNESP]Borges, Cibele dos Santos [UNESP]Rosa, Josiane de Lima [UNESP]Pacheco, Tainá Louise [UNESP]Figueiredo, Thamiris Moreira [UNESP]Leite, Gabriel Adan AraújoGuerra, Marina Trevizan [UNESP]Anselmo-Franci, Janete AparecidaKlinefelter, Gary RobertKempinas, Wilma De Grava [UNESP]2020-12-12T02:36:00Z2020-12-12T02:36:00Z2020-07-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article947-964http://dx.doi.org/10.1002/jat.3955Journal of Applied Toxicology, v. 40, n. 7, p. 947-964, 2020.1099-12630260-437Xhttp://hdl.handle.net/11449/20156810.1002/jat.39552-s2.0-85079704475Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Applied Toxicologyinfo:eu-repo/semantics/openAccess2021-10-22T20:28:35Zoai:repositorio.unesp.br:11449/201568Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T17:00:16.403308Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats |
title |
Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats |
spellingShingle |
Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats e Silva, Patrícia Villela [UNESP] fertility male rat reproductive toxicity rosuvastatin sibutramine |
title_short |
Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats |
title_full |
Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats |
title_fullStr |
Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats |
title_full_unstemmed |
Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats |
title_sort |
Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats |
author |
e Silva, Patrícia Villela [UNESP] |
author_facet |
e Silva, Patrícia Villela [UNESP] Borges, Cibele dos Santos [UNESP] Rosa, Josiane de Lima [UNESP] Pacheco, Tainá Louise [UNESP] Figueiredo, Thamiris Moreira [UNESP] Leite, Gabriel Adan Araújo Guerra, Marina Trevizan [UNESP] Anselmo-Franci, Janete Aparecida Klinefelter, Gary Robert Kempinas, Wilma De Grava [UNESP] |
author_role |
author |
author2 |
Borges, Cibele dos Santos [UNESP] Rosa, Josiane de Lima [UNESP] Pacheco, Tainá Louise [UNESP] Figueiredo, Thamiris Moreira [UNESP] Leite, Gabriel Adan Araújo Guerra, Marina Trevizan [UNESP] Anselmo-Franci, Janete Aparecida Klinefelter, Gary Robert Kempinas, Wilma De Grava [UNESP] |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade Estadual de Campinas (UNICAMP) Universidade de São Paulo (USP) US Environmental Protection Agency |
dc.contributor.author.fl_str_mv |
e Silva, Patrícia Villela [UNESP] Borges, Cibele dos Santos [UNESP] Rosa, Josiane de Lima [UNESP] Pacheco, Tainá Louise [UNESP] Figueiredo, Thamiris Moreira [UNESP] Leite, Gabriel Adan Araújo Guerra, Marina Trevizan [UNESP] Anselmo-Franci, Janete Aparecida Klinefelter, Gary Robert Kempinas, Wilma De Grava [UNESP] |
dc.subject.por.fl_str_mv |
fertility male rat reproductive toxicity rosuvastatin sibutramine |
topic |
fertility male rat reproductive toxicity rosuvastatin sibutramine |
description |
Many obese patients are exposed to hypolipidemic and serotonin-norepinephrine reuptake inhibitor (SNRI) drugs. Statins are one of the most marketed drugs in the world to treat dyslipidemia, while sibutramine, a SNRI drug, is prescribed in some countries to treat obesity and is detected as an additive in many adulterated weight loss supplements marketed worldwide. Previous studies reported adverse effects of isolated exposure to these drugs on male rat reproductive parameters. In the present work, we further investigated male reproductive toxicity of these drugs, administered in isolation or combination in adult rats for a longer period of treatment. Adult male rats (90 days) were treated (gavage) for 70 days with saline and dimethyl sulfoxide (control), sibutramine (10 mg/kg), rosuvastatin (5 mg/kg), or rosuvastatin combined with sibutramine. Sibutramine alone or with rosuvastatin, promoted a reduction in food intake and body weight gain, weight of the epididymis, ventral prostate and seminal vesicle; as well as decreased sperm reserves and transit time through the epididymis; androgen depletion; and increased index of cytoplasmic droplet. The rosuvastatin-treated group showed reduced frequency of ejaculation. Exposure to this drug alone or combined with sibutramine impaired epididymal morphology. Co-exposed rats had altered epididymal morphometry, and seminal vesicle and testis weights. The rats also showed decreased fertility after natural mating and a trend toward a delay in ejaculation, suggesting a small synergistic effect of these drugs. Given the greater reproductive efficiency of rodents, the results obtained in the present study raise concern regarding possible fertility impairment in men taking statins and SNRI drugs. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-12T02:36:00Z 2020-12-12T02:36:00Z 2020-07-01 |
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/10.1002/jat.3955 Journal of Applied Toxicology, v. 40, n. 7, p. 947-964, 2020. 1099-1263 0260-437X http://hdl.handle.net/11449/201568 10.1002/jat.3955 2-s2.0-85079704475 |
url |
http://dx.doi.org/10.1002/jat.3955 http://hdl.handle.net/11449/201568 |
identifier_str_mv |
Journal of Applied Toxicology, v. 40, n. 7, p. 947-964, 2020. 1099-1263 0260-437X 10.1002/jat.3955 2-s2.0-85079704475 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Applied Toxicology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
947-964 |
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 |
|
_version_ |
1808128736488325120 |