Bellentani Fernanda F, Fernandes Glaura S A, Perobelli Juliana E, Pacini Enio S A, Kiguti Luiz R A, Pupo André S, Kempinas Wilma D G
Department of Morphology, Institute of Biosciences, UNESP-Univ Estadual Paulista, Distrito de Rubião Jr. s/n, Botucatu, SP-Brazil.
J Androl. 2011 Nov-Dec;32(6):718-24. doi: 10.2164/jandrol.111.013466. Epub 2011 Jul 15.
Sibutramine is a drug globally used for the treatment of obesity. The aim of this study was to investigate male reproductive disorders caused by sibutramine in adult rats. Wistar rats were treated for 28 consecutive days (gavage) with 10 mg/kg of sibutramine. Control animals received only vehicle (dimethylsulfoxide and saline). The rats were sacrificed for evaluation of body and reproductive organ weights, sperm parameters, hormone levels (luteinizing hormone, follicle-stimulating hormone, and testosterone), testicular and epididymal histopathology, sexual behavior, fertility and in vitro contractility of the epididymal duct. Sibutramine decreased (P < .05) weights of the epididymis and ventral prostate, but not of other reproductive organs. The sperm number and transit time in the epididymal cauda were decreased (P < .001), but the daily sperm production was not altered. Moreover, morphology and sperm motility, histopathology of the testes and epididymis, sexual behavior, fertility, and serum hormone levels were not altered by the treatment. Sibutramine increased the potency of norepinephrine and, per se, increased the mechanical activity of the epididymal duct in vitro. Thus, although sibutramine in these experimental conditions did not interfere with the reproductive process of rats, it provoked acceleration of the sperm transit time and a decrease in the sperm reserves in the epididymal cauda. This alteration is probably related to the sympathomimetic effect of this drug, as shown by the in vitro assays. In humans, use of this drug might present a threat for male fertility because sperm reserves in men are naturally lower than those in rats.
西布曲明是一种全球用于治疗肥胖症的药物。本研究的目的是调查西布曲明对成年大鼠雄性生殖系统紊乱的影响。将Wistar大鼠连续28天（灌胃）给予10mg/kg西布曲明。对照动物仅给予溶媒（二甲亚砜和生理盐水）。处死大鼠以评估体重和生殖器官重量、精子参数、激素水平（促黄体生成素、促卵泡生成素和睾酮）、睾丸和附睾组织病理学、性行为、生育能力以及附睾管的体外收缩性。西布曲明降低了（P<0.05）附睾和腹侧前列腺的重量，但对其他生殖器官重量无影响。附睾尾部的精子数量和转运时间减少（P<0.001），但每日精子生成量未改变。此外，治疗对精子形态和活力、睾丸和附睾组织病理学、性行为、生育能力以及血清激素水平均无影响。西布曲明增强了去甲肾上腺素的作用，本身增加了附睾管的体外机械活性。因此，尽管在这些实验条件下西布曲明不干扰大鼠的生殖过程，但它导致精子转运时间加快和附睾尾部精子储备减少。如体外试验所示，这种改变可能与该药物的拟交感神经作用有关。在人类中，使用这种药物可能对男性生育能力构成威胁，因为男性的精子储备天然低于大鼠。
