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在雄性大鼠的青春期期间给予 Lisdexamfetamine dimesylate 会损害雄性青春期大鼠肾脏中的炎症机制、抗氧化活性和细胞凋亡过程。

Lisdexamfetamine dimesylate-exposition in male rats during the peripubertal period impairs inflammatory mechanisms, antioxidant activity, and apoptosis process in kidneys of male pubertal rats.

机构信息

Department of General Biology, Biological Sciences Center, State University of Londrina - UEL, Londrina, Brazil.

Department of Pathology, Biological Sciences Center, State University of Londrina - UEL, Londrina, Brazil.

出版信息

J Biochem Mol Toxicol. 2024 Aug;38(8):e23781. doi: 10.1002/jbt.23781.

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

右苯丙胺硫酸盐(LDX)是右旋苯丙胺的前体药物,已被广泛推荐用于治疗注意力缺陷多动障碍(ADHD)。目前文献中尚无关于 LDX 在肾脏中可能产生毒性作用的相关数据。因此,本研究旨在评估 LDX 暴露对雄性青春期 Wistar 大鼠肾脏形态、氧化应激、细胞死亡和炎症参数的影响,因为肾脏是与大多数药物排泄相关的器官。为此,将 20 只雄性 Wistar 大鼠随机分为两组:LDX 组-接受 11.3mg/kg/天的 LDX;对照组-接受自来水。动物从出生后第 25 天到 65 天经灌胃给药。在第 66 天,收集血浆进行生化测定,收集肾脏进行炎症谱、氧化状态、细胞死亡的测定,并进行组织化学和形态学分析。我们的结果表明,接受 LDX 的组中,标记细胞死亡的细胞数量增加,近端和远端曲管的平均直径减小。此外,我们的结果还显示 MPO 和 NAG 活性增加,表明存在炎症反应。氧化状态表明抗氧化系统正常工作,避免了氧化应激。因此,在青春期期间,雄性大鼠暴露于 LDX 会导致青春期年龄的肾脏变化,涉及炎症机制、抗氧化活性和细胞凋亡过程。

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