Effects of exposure to lisdexamfetamine dimesylate on hepatic parameters of pubertal rats

Lisdexamfetamine dimesylate (LDX) is a psychostimulant, that has been widely recommended in recent years for the treatment of Attention-Deficit/Hyperactivity Disorder. The present study aims to evaluate the effects of LDX administration on the hepatic morphophysiology of pubertal Wistar rats, since the liver plays a central role in systemic metabolism. Male Wistar rats were randomly distributed into two experimental groups: LDX group (LDX) - received 11.3 mg/kg/day of LDX diluted in tap water; and the Control group (C) - received tap water only. Animals were treated by gavage during puberty, from postnatal day (PND) 25 to PND 65. The results showed that administration of LDX decreased white adipose tissue weight without altering overall body weight gain. Plasma biochemical analysis demonstrated an increase in plasma total cholesterol and in the concentration of hepatic transaminases in LDX rats. In addition, LDX animals exhibited an increase in N-acetyl-β-D-glucosaminidase activity, indirectly indicating macrophage recruitment to the liver. This study shows that daily exposure to LDX during puberty causes early liver inflammation and damage due, in part, to increased hepatic transaminases and associated with indirect signs of macrophage recruitment. This finding highlights the importance of monitoring the indiscriminate use of amphetamines and alerting patients to possible liver disorders.