Abstract：
Lisdexamfetamine dimesylate (LDX) is a prodrug of dextroamphetamine, which has been widely recommended for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). There are still no data in the literature relating the possible toxic effects of LDX in the kidney. Therefore, the present study aims to evaluate the effects of LDX exposure on morphological, oxidative stress, cell death and inflammation parameters in the kidneys of male pubertal Wistar rats, since the kidneys are organs related to the excretion of most drugs. For this, twenty male Wistar rats were distributed randomly into two experimental groups: LDX group-received 11,3 mg/kg/day of LDX; and Control group-received tap water. Animals were treated by gavage from postnatal day (PND) 25 to 65. At PND 66, plasma was collected to the biochemical dosage, and the kidneys were collected for determinations of the inflammatory profile, oxidative status, cell death, and for histochemical, and morphometric analyses. Our results show that there was an increase in the number of cells marked for cell death, and a reduction of proximal and distal convoluted tubules mean diameter in the group that received LDX. In addition, our results also showed an increase in MPO and NAG activity, indicating an inflammatory response. The oxidative status showed that the antioxidant system is working undisrupted and avoiding oxidative stress. Therefore, LDX-exposition in male rats during the peripubertal period causes renal changes in pubertal age involving inflammatory mechanisms, antioxidant activity and apoptosis process.
摘要：
Lisdexamfetamine二甲磺酸盐（LDX）是右旋苯丙胺的前药，已被广泛推荐用于治疗注意力缺陷/多动障碍（ADHD）。文献中仍然没有关于LDX在肾脏中可能的毒性作用的数据。因此,本研究旨在评估LDX暴露对形态学的影响，氧化应激，雄性青春期Wistar大鼠肾脏的细胞死亡和炎症参数，因为肾脏是与大多数药物排泄有关的器官。为此，将20只雄性Wistar大鼠随机分为两个实验组：LDX组接受11,3mg/kg/天的LDX；对照组接受自来水。从出生后第25天至第65天(PND)通过管饲法处理动物。在PND66，血浆被收集到生化剂量，收集肾脏以确定炎症特征，氧化状态，细胞死亡,对于组织化学，和形态计量学分析。我们的结果表明，标记为细胞死亡的细胞数量增加，在接受LDX的组中，近端和远端曲小管平均直径减少。此外,我们的结果还显示MPO和NAG活性增加，表明炎症反应。氧化状态表明，抗氧化系统工作不中断，避免氧化应激。因此,在青春期期间，雄性大鼠的LDX-exposition引起青春期肾脏变化，涉及炎症机制，抗氧化活性和凋亡过程。
