Toxicology of long‐term and high-dose administration of methylphenidate on the kidney tissue – a histopathology and molecular study

Abstract

The present study aims to assess the influences of oral methylphenidate on kidney function and structure versus vehicle treatment in adult male rats. In this study, thirty adult male rats equally into two treatment groups divided randomly, and among them, MPH has been administered for 21 days, at doses of 20 mg/kg, and the control group has received salin. In renal, under the effect of MPH applying quantitative real-time PCR, we analyzed nephrotoxicity-related molecular pathways like autophagy, inflammation, and apoptosis. Moreover, the levels of GSH, CAT, and SOD were investigated as antioxidant enzymes. Afterward, stereological analysis in MPH-treated rats has been performed. Analysis of qPCR displayed inflammation, impaired autophagy, and enhanced apoptosis with histological changes in the kidney’s tissue, also an important rise in the antioxidant enzymes’ level. Besides, 20 mg/kg of MPH led to a decline in the mean of Bowman’s space thickness and renal corpuscle’s volume in comparison to the control rats. Collectively, our histological and molecular data implicit that in the kidney region, administrating of MPH evoked discriminative expression alterations in nephrotoxicity-associated signaling cascades, specifically autophagy, inflammation, and apoptosis paired with important damage to kidney tissue.

Graphical Abstract

Keywords:

• Autophagy
• apoptosis
• inflammation
• kidney
• methylphenidate
• nephrotoxicity

Acknowledgment

Hereby, researchers appreciate the School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran, for the given support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data is available from the corresponding authors upon request.

Additional information

Funding

The study was funded by Leishmaniasis Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran [98157].