Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats

Autor: Gabriel Adan Araújo Leite, Marina T. Guerra, Tainá Louise Pacheco, Cibele dos Santos Borges, Gary R. Klinefelter, Patrícia Villela e Silva, Thamiris Moreira Figueiredo, Janete Aparecida Anselmo-Franci, Josiane de Lima Rosa, Wilma De Grava Kempinas
Přispěvatelé: Universidade Estadual Paulista (Unesp), Universidade Estadual de Campinas (UNICAMP), Universidade de São Paulo (USP), US Environmental Protection Agency
Rok vydání: 2020
Předmět:
Zdroj: Scopus
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
ISSN: 1099-1263
0260-437X
DOI: 10.1002/jat.3955
Popis: Made available in DSpace on 2020-12-12T02:36:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-07-01 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) 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. Department of Morphology Institute of Biosciences São Paulo State University - UNESP Graduate Program in Cell and Structural Biology Institute of Biology State University of Campinas – UNICAMP Department of Morphology Physiology and Basic Pathology School of Dentistry of Ribeirão Preto University of São Paulo – USP Reproductive Toxicity Branch Toxicity Assessment Division National Health and Environmental Effects Research Laboratory Office of Research and Development US Environmental Protection Agency Department of Morphology Institute of Biosciences São Paulo State University - UNESP FAPESP: 2014/15566-2 CNPq: 308842/2013-8 CNPq: 312118/2017-1
Databáze: OpenAIRE
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