ArticleCellular and molecular neurobiology2011
Experimental evidence that methylmalonic acid provokes oxidative damage and compromises antioxidant defenses in nerve terminal and striatum of young rats.
Article in Cellular and molecular neurobiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 61 citations in OpenAlex.
- Disturbances of Mitochondrial Functions and Oxidative Stress Induction in Methylmalonic and Propionic Acidemias: A Critical Role for Metabolite Accumulation.International journal of molecular sciences · 2026Review
- The mediating role of inflammation and nutrition metabolism in the methylmalonic acid-stroke association.Clinics (Sao Paulo, Brazil) · 2026Article
- Glutamatergic Neurotransmission Disruption as a Pathomechanism of Brain Damage in Disorders of Amino Acid and Organic Acid Metabolism: Insights from Animal and Cellular Studies.Neurochemical research · 2026Review
- Mechanisms of Microglial NLRP3 Inflammasome Activation by Methylmalonic Acid in Methylmalonic Acidemia.Mediators of inflammation · 2026Article
- Metabolic toxicity and neurological dysfunction in methylmalonic acidemia: from mechanisms to therapeutics.Molecular medicine (Cambridge, Mass.) · 2025Review
- Neurodegenerative biomarkers and inflammation in patients with propionic and methylmalonic acidemias: effect of L-carnitine treatment.Metabolic brain disease · 2024Article
- Mitochondrion-based organellar therapies for central nervous system diseases.Cell communication and signaling : CCS · 2024Review
- Associations of methylmalonic acid and depressive symptoms with mortality: a population-based study.Translational psychiatry · 2024Article
- Pathophysiological mechanisms of complications associated with propionic acidemia.Pharmacology & therapeutics · 2023Review
- Clinical Pathobiochemistry of Vitamin BNutrients · 2023Review
- Mitochondrial transplantation ameliorates hippocampal damage following status epilepticus.Animal models and experimental medicine · 2023Article
- A Lower Serum Antioxidant Capacity as a Distinctive Feature for Women with HER2+ Breast Cancer: A Preliminary Study.Cancers · 2022Article
- Mechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative Review.International journal of molecular sciences · 2022Review
- Toxic Metabolites and Inborn Errors of Amino Acid Metabolism: What One Informs about the Other.Metabolites · 2022Review
- Correlations between circulating methylmalonic acid levels and all-cause and cause-specific mortality among patients with diabetes.Frontiers in nutrition · 2022Article
- Effects of Vitamin BAntioxidants (Basel, Switzerland) · 2021Article
- The Effect of Methylmalonic Acid Treatment on Human Neuronal Cell Coenzyme QInternational journal of molecular sciences · 2020Article
- Proteomics Reveals that Methylmalonyl-CoA Mutase Modulates Cell Architecture and Increases Susceptibility to Stress.International journal of molecular sciences · 2020Article
- Differential metabolic markers associated with primary open-angle glaucoma and cataract in human aqueous humor.BMC ophthalmology · 2020Article
- The Deleterious Impact of Interleukin 9 to Hepatorenal Physiology.Inflammation · 2019Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Methylmalonic acidemia and propionic acidemia are organic acidemias biochemically characterized by predominant tissue accumulation of methylmalonic acid (MMA) and propionic acid (PA), respectively. Affected patients present predominantly neurological symptoms, whose pathogenesis is not yet fully established. In the present study we investigated the in vitro effects of MMA and PA on important parameters of lipid and protein oxidative damage and on the production of reactive species in synaptosomes from cerebrum of developing rats. Synaptosomes correspond to nerve terminals that have been used to investigate toxic properties of compounds on neuronal cells. The in vivo effects of intrastriatal injection of MMA and PA on the same parameters and on enzymatic antioxidant defenses, were also studied. MMA-induced in vitro and in vivo lipid peroxidation and protein oxidative damage. Furthermore, the lipid oxidative damage was attenuated or prevented, pending on the doses utilized, by the free radical scavengers α-tocopherol, melatonin and by the NMDA glutamate receptor antagonist MK-801, implying the involvement of reactive species and glutamate receptor activation in these effects. In addition, 2',7'-dichlorofluorescein diacetate oxidation was significantly increased in synaptosomes by MMA, reinforcing that reactive species generation is elicited by this organic acid. We also verified that glutathione peroxidase activity was inhibited by intrastriatal MMA injection. In contrast, PA did not induce any significant effect on all parameters examined in vitro and in vivo, implying a selective action for MMA. The present data demonstrate that oxidative stress is induced by MMA in vitro in nerve terminals and in vivo in striatum, suggesting the participation of neuronal cells in MMA-elicited oxidative damage.
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