Evidence of methylphenidate effect on mitochondria, redox homeostasis, and inflammatory aspects: Insights from animal studies

Luiza N Foschiera; Felipe Schmitz; Angela T S Wyse

doi:10.1016/j.pnpbp.2022.110518

Evidence of methylphenidate effect on mitochondria, redox homeostasis, and inflammatory aspects: Insights from animal studies

Prog Neuropsychopharmacol Biol Psychiatry. 2022 Jun 8:116:110518. doi: 10.1016/j.pnpbp.2022.110518. Epub 2022 Jan 29.

Authors

Luiza N Foschiera¹, Felipe Schmitz², Angela T S Wyse³

Affiliations

¹ Neuroprotection and Neurometabolic Diseases Laboratory (Wyse's Lab), Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
² Neuroprotection and Neurometabolic Diseases Laboratory (Wyse's Lab), Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Post-graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
³ Neuroprotection and Neurometabolic Diseases Laboratory (Wyse's Lab), Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Post-graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: wyse@ufrgs.br.

PMID: 35092763
DOI: 10.1016/j.pnpbp.2022.110518

Abstract

Methylphenidate (MPH) is a central nervous system (CNS) stimulant known for its effectiveness in the treatment of Attention Deficit Hyperactivity Disorder (ADHD), a neuropsychiatric condition that has a high incidence in childhood and affects behavior and cognition. However, the increase in its use among individuals who do not present all the diagnostic criteria for ADHD has become a serious public health problem since the neurological and psychiatric consequences of this unrestricted use are not widely known. In addition, since childhood is a critical period for the maturation of the CNS, the high prescription of MPH for preschool children also raises several concerns. This review brings new perspectives on how MPH (in different doses, routes of administration and ages) affects the CNS, focusing on animal studies that evaluated changes in mitochondrial (bioenergetics), redox balance and apoptosis, as well as inflammatory parameters. MPH alters brain energy homeostasis, increasing glucose consumption and impairing the activity of enzymes in the Krebs cycle and electron transport chain, as well as ATP levels and Na⁺,K⁺-ATPase activity. MPH induces oxidative stress, increasing the levels of reactive oxygen and nitrogen species and altering enzymatic and non-enzymatic antioxidant defenses, which, consequently, is related to damage to proteins, lipids, and DNA. Among the harmful effects of MPH, studies also demonstrate its ability to induce inflammation as well as alter the apoptosis pathway. It is important to highlight that age, treatment time, administration route, and dose are factors that can influence MPH effects. However, young animals seem to be more susceptible to damage caused by MPH. It is possible that changes in mitochondrial function and markers of status oxidative, apoptosis and inflammation may be exerting important mechanisms associated with MPH toxicity and, therefore, the unrestricted use of this drug can cause brain damage.

Keywords: Apoptosis; Inflammation; Methylphenidate; Mitochondrial dysfunction; Oxidative stress.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Attention Deficit Disorder with Hyperactivity* / drug therapy
Central Nervous System Stimulants* / therapeutic use
Homeostasis
Inflammation / metabolism
Methylphenidate* / adverse effects
Mitochondria / metabolism
Oxidation-Reduction

Substances

Central Nervous System Stimulants
Methylphenidate