da Silva Raquel Frenedoso, Borges Cibele dos Santos, Villela E Silva Patrícia, Missassi Gabriela, Kiguti Luiz Ricardo Almeida, Pupo André Sampaio, Barbosa Junior Fernando, Anselmo-Franci Janete Aparecida, Kempinas Wilma De Grava
Department of Morphology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), 18618-970 Botucatu, SP, Brazil.
Department of Pharmacology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), 18618-970 Botucatu, SP, Brazil.
Oxid Med Cell Longev. 2016;2016:4257498. doi: 10.1155/2016/4257498. Epub 2015 Dec 29.
Arsenic trioxide (As2O3) has shown effectiveness in treatment of leukemia but is also associated with reproductive toxicity. Since remediation with N-acetylcysteine (NAC) may mitigate the adverse effects caused by exposure, we assessed the effects of As2O3 and its potential reversibility after exposure cessation or coadministration of NAC. Animals received 0.3 or 3.0 mg/Kg/day of As2O3 subcutaneously and 40 mM of NAC in tap water. As2O3 treatment impaired spermatogenesis and sperm motility and decreased seminal vesicle weight and testosterone serum levels; after suspension of treatment, these parameters remained altered. When NAC was administered, animals showed improvement in sperm parameters and seminal vesicle weight. In vitro epididymal contractility was increased in As2O3-treated animals. We concluded that As2O3 is toxic to the male mouse genital system by compromising sperm quality and quantity; these effects persisted even after suspension of the treatment. However, the coadministration of NAC ameliorates the harmful effects of the drug on the male genital system.
三氧化二砷(As2O3)已显示出对白血病的治疗效果,但也与生殖毒性有关。由于用N-乙酰半胱氨酸(NAC)进行补救可能减轻暴露所引起的不良反应,我们评估了As2O3的影响及其在停止暴露或同时给予NAC后的潜在可逆性。动物皮下注射0.3或3.0毫克/千克/天的As2O3,并在自来水中给予40毫摩尔的NAC。As2O3处理损害精子发生和精子活力,降低精囊重量和血清睾酮水平;停止治疗后,这些参数仍未恢复。当给予NAC时,动物的精子参数和精囊重量有所改善。As2O3处理的动物体外附睾收缩力增加。我们得出结论,As2O3通过损害精子质量和数量对雄性小鼠生殖系统有毒性;即使在停止治疗后,这些影响仍然存在。然而,同时给予NAC可改善该药物对雄性生殖系统的有害影响。