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

Author(s)

e Silva, Patricia Villela ^[1] ; Borges, Cibele dos Santos ^[1] ; Rosa, Josiane de Lima ^[1] ; Pacheco, Taina Louise ^[1] ; Figueiredo, Thamiris Moreira ^[1] ; Leite, Gabriel Adan Araujo ^[2] ; Guerra, Marina Trevizan ^[1] ; Anselmo-Franci, Janete Aparecida ^[3] ; Klinefelter, Gary Robert ^[4] ; Kempinas, Wilma De Grava ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Inst Biosci, Dept Morphol, Botucatu, SP - Brazil

^[2] State Univ Campinas UNICAMP, Inst Biol, Grad Program Cell & Struct Biol, Campinas, SP - Brazil

^[3] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Ribeirao Preto, SP - Brazil

^[4] US EPA, Reprod Tox Branch, Tox Assessment Div, Natl Hlth & Environm Effects Res Lab, Off Res & De, Durham, NC 27709 - USA

• Document type: Journal article
• Source: JOURNAL OF APPLIED TOXICOLOGY; v. 40, n. 7 FEB 2020.
• Web of Science Citations: 1

Abstract

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. (AU)

• FAPESP's process: 14/15566-2 - Effects of subchronic and prolonged exposure to sibutramine and/or rosuvastatin on reproductive parameters and fertility of adult male Wistar rats
• Grantee: Patrícia Villela e Silva
• Support Opportunities: Scholarships in Brazil - Doctorate