ArticleMetabolic brain disease2021
The metabolic effect of α-ketoisocaproic acid: in vivo and in vitro studies.
Article in Metabolic brain disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Systemic dual-gene therapy reverses biochemical intoxication in the central metabolic compartment of Bckdha-/- mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Neuroprotective Role of Ketamine in Reducing Neuroinflammation and Enhancing Neuroplasticity Against a Cortisol-Induced In Vitro Stress Model.Molecular neurobiology · 2025Article
- Minocycline Protects Against Oxidative Stress in a Model of Maple Syrup Urine Disease.Neurochemical research · 2025Article
- LDL Exposure Disrupts Mitochondrial Function and Dynamics in a Hippocampal Neuronal Cell Line.Molecular neurobiology · 2025Article
- α-Ketoisocaproic Acid Disrupts Mitochondrial Bioenergetics in the Brain of Neonate Rats: Molecular Modeling Studies of α-ketoglutarate Dehydrogenase Subunits Inhibition.Neurochemical research · 2025Article
- Multi-omics integration reveals gut microbiota dysbiosis and metabolic alterations of cerebrospinal fluid in children with epilepsy.Frontiers in microbiology · 2025Article
- Genotypic and phenotypic spectrum of maple syrup urine disease in Zhejiang of China.QJM : monthly journal of the Association of Physicians · 2024Article
- In Vivo Intracerebral Administration of α-Ketoisocaproic Acid to Neonate Rats Disrupts Brain Redox Homeostasis and Promotes Neuronal Death, Glial Reactivity, and Myelination Injury.Molecular neurobiology · 2024Article
- Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis.Open life sciences · 2024Article
- Definition of the Neurotoxicity-Associated Metabolic Signature Triggered by Berberine and Other Respiratory Chain Inhibitors.Antioxidants (Basel, Switzerland) · 2023Article
- Acute effects of intracerebroventricular administration of α-ketoisocaproic acid in young rats on inflammatory parameters.Metabolic brain disease · 2023Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Maple syrup urine disease (MSUD) is characterized by a deficiency in the mitochondrial branched-chain α-keto acid dehydrogenase complex activity and, consequently, accumulation of the branched-chain amino acids and their respective branched-chain α-keto acids in fluids and the tissue. MSUD clinical symptoms include neurological alterations. KIC is considered one of the significant neurotoxic metabolites since its increased plasma concentrations are associated with neurological symptoms. We evaluated the effect of KIC intracerebroventricular (ICV) injection in hippocampal mitochondria function in rats. We also investigated the impact of KIC in cells' metabolic activity (using MTT assay) and reactive species (RS) production in HT-22 cells. For this, thirty-day-old male rats were bilaterally ICV injected with KIC or aCSF. Thus, 1 hour after the administration, animals were euthanized, and the hippocampus was harvested for measured the activities of mitochondrial respiratory chain enzymes and RS production. Furthermore, HT-22 cells were incubated with KIC (1-10 mM) in 6, 12, and 24 h. Mitochondrial complexes activities were reduced, and the formation of RS was increased in the hippocampus of rats after KIC administration. Moreover, KIC reduced the cells' metabolic ability to reduce MTT and increased RS production in hippocampal neurons. Impairment in hippocampal mitochondrial function seems to be involved in the neurotoxicity induced by KIC.
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