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Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats
Author(s) -
Silva Patrícia Villela,
Borges Cibele dos Santos,
Rosa Josiane de Lima,
Pacheco Tainá Louise,
Figueiredo Thamiris Moreira,
Leite Gabriel Adan Araújo,
Guerra Marina Trevizan,
AnselmoFranci Janete Aparecida,
Klinefelter Gary Robert,
Kempinas Wilma De Grava
Publication year - 2020
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3955
Subject(s) - sibutramine , epididymis , rosuvastatin , endocrinology , medicine , reproductive toxicity , pharmacology , sperm , toxicity , weight loss , andrology , obesity
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.