Work

Valproate Damaging Effect on Erythrocyte Metabolism as a Decisive Factor in the Development of Encephalopathy

Year: 2025

Type: article

Abstract: BACKGROUND: Valproic acid (VPA) is a mainstay of treatment for epilepsy. Although VPA is generally considered well tolerated, it has serious adverse effects related to the pathological impact on cerebral perfusion and oxidative metabolism, leading to progressive encephalopathy. Erythrocytes directly deliver oxygen to the tissues. To understand how the brain pathology may be related to limited oxygenation, it is important to determine whether VPA-related changes occur in the intracellular erythrocyte metabolism responsible for the oxygen transport function. METHODS: To determine whether different therapeutic VPA doses affect major metabolic pathways in rat erythrocytes, the activity of rate-limiting enzymes and levels of metabolites of glycolysis, the Rapoport-Luebering shunt, the pentose phosphate pathway and the antioxidant systems were measured. RESULTS: Our data showed that VPA-induced G6PD inhibition leads to profound oxidative stress, increased MetHb formation and decreased 2,3-DPG and ATP levels in erythrocytes that underlie the loss of their oxygen transport function, thus being a cause of a brain energy crisis that precedes encephalopathy. CONCLUSIONS: The measurement of parameters in metabolic pathways modulating the redox-signaling and oxygen-carrying capacity of erythrocytes is needed for further elucidation of complex mechanisms underlying VPA-induced brain hypoperfusion and encephalopathy.

Source: Biomolecules

DOI: 10.3390/biom15040588

Authors: Lyudmila Tikhonova, Eugene Maevsky, Carmina Montoliu, Elena Kosenko

Institutions: Russian Academy of Sciences, Institute of Theoretical and Experimental Biophysics, Universitat de València, INCLIVA Health Research Institute

Language: English

Topic: Pharmacological Effects and Toxicity Studies

Subfield: Pediatrics, Perinatology and Child Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258