Abstract：
Lisdexamfetamine (LDX) is a d-amphetamine prodrug used to treat attention deficit and hyperactivity disorder, a common neurodevelopmental disorder in children and adolescents. Due to its action mediated by elevated levels of catecholamines, mainly dopamine and noradrenaline, which influence hormonal regulation and directly affect the gonads, this drug may potentially disrupt reproductive performance. This study evaluated the effects of exposure to LDX from the juvenile to peripubertal period (critical stages of development) on systemic and reproductive toxicity parameters in male rats. Male Wistar rats (23 days old) were treated with 0; 5.2; 8.6 or 12.1 mg/kg/day of LDX from post-natal day (PND) 23 to 53, by gavage. LDX treatment led to reduced daily food and water consumption, as well as a decrease in social behaviors. The day of preputial separation remained unaltered, although the treated animals exhibited reduced weight. At PND 54, the treated animals presented signs of systemic toxicity, evidenced by a reduction in body weight gain, increase in the relative weight of the liver, spleen, and seminal gland, reduction in erythrocyte and leukocyte counts, reduced total protein levels, and disruptions in oxidative parameters. In adulthood, there was an increase in immobile sperm, reduced sperm count, morphometric changes in the testis, and altered oxidative parameters, without compromising male sexual behavior and fertility. These findings showed that LDX-treatment during the juvenile and peripubertal periods induced immediate systemic toxicity and adversely influenced reproductive function in adult life, indicating that caution is necessary when prescribing this drug during the peripubertal phase.
摘要：
Lisdexamfetamine（LDX）是一种d-苯丙胺前药，用于治疗注意力缺陷和多动障碍，儿童和青少年常见的神经发育障碍。由于其作用由儿茶酚胺水平升高介导，主要是多巴胺和去甲肾上腺素,影响荷尔蒙调节并直接影响性腺，这种药物可能会破坏生殖性能。这项研究评估了从幼年到青春期（发育的关键阶段）暴露于LDX对雄性大鼠全身和生殖毒性参数的影响。雄性Wistar大鼠(23日龄)从出生后第23至53天(PND)用0、5.2、8.6或12.1mg/kg/天的LDX通过管饲法处理。LDX治疗导致每日食物和水消耗减少，以及社会行为的减少。包皮分离的日子没有改变，尽管治疗的动物表现出体重减轻。在PND54，接受治疗的动物出现全身毒性的迹象，体重增加的减少证明了这一点，增加肝脏的相对重量，脾,脾和精腺，红细胞和白细胞计数减少，降低总蛋白质水平，和氧化参数的破坏。成年后,不动的精子增加了，精子数量减少,睾丸的形态变化,改变了氧化参数，不影响男性性行为和生育能力。这些发现表明，在青少年和青春期期间，LDX治疗会立即引起全身毒性，并对成年后的生殖功能产生不利影响。这表明在青春期期间开这种药物时需要谨慎。
