Lisdexamfetamine dimesylate-exposition in male rats during the peripubertal period impairs inflammatory mechanisms, antioxidant activity, and apoptosis process in kidneys of male pubertal rats.
João Vinícius Honório da SilvaRafaela Pires ErthalIsadora Chagas VercelloneDayane Priscila Dos SantosCamila Rodrigues FerrazRicardo Luís Nascimento de MatosLuís Eduardo Duarte GonçalvesAna Paula Frederico Rodrigues Loureiro BracarenseWaldiceu Aparecido VerriNiels Olsen Saraiva CâmaraFábio Goulart de AndradeGlaura Scantamburlo Alves FernandesPublished in: Journal of biochemical and molecular toxicology (2024)
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.
Keyphrases
- oxidative stress
- cell death
- cell cycle arrest
- attention deficit hyperactivity disorder
- induced apoptosis
- autism spectrum disorder
- inflammatory response
- diabetic rats
- dna damage
- ischemia reperfusion injury
- working memory
- pi k akt
- systematic review
- signaling pathway
- preterm infants
- endoplasmic reticulum stress
- minimally invasive
- machine learning
- lps induced
- cancer therapy
- electronic health record
- replacement therapy
- newly diagnosed
- optic nerve
- anti inflammatory
- immune response