Cited by 189Coenzyme Q10 studies and effectsMitochondrial Function and PathologyNeurological Disorders and Treatments

Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate

Beal, M. Flint, Henshaw, D. Ross, Jenkins, Bruce G., Rosen, Bruce R., Schulz, Jourg B.·1994·Annals of Neurology

Abstract

A potential mechanism of neuronal injury in neurodegenerative diseases is a defect in energy metabolism that may lead to slow excitotoxic neuronal death. Consistent with this possibility, we showed that specific inhibitors of the electron transport chain produce excitotoxic lesions in vivo. In the present study we examined whether agents that improve energy metabolism can block lesions produced by the mitochondrial toxin malonate. Striatal lesions produced by the complex II inhibitor malonate were blocked in a dose‐dependent manner by oral pretreatment with coenzyme Q 10. Administration of nicotinamide by Alzet pump for 1 week attenuated malonate‐induced lesions, but riboflavin had no effect. Administration of nicotinamide intraperitoneally just prior to and following induction of the lesions produced dose‐dependent neuroprotection. A combination of coenzyme Q 10 with nicotinamide was more effective than either compound alone, as shown by both lesion size and magnetic resonance imaging in vivo. Both coenzyme Q 10 and nicotinamide blocked adenosine triphosphate depletions and lactate increases. These results confirm that mitochondrial toxins produce striatal excitotoxic lesions by a mechanism involving energy depletion in vivo. Furthermore, they suggest novel neuroprotective strategies that may be useful in the treatment of both mitochondrial encephalopathies and neurodegenerative diseases.

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Crossref · 10.1002/ana.410360613

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  • Oral administration of CoQ10 exerts significant neuroprotective effects against striatal lesions in rats produced by aminoxyacetic acid, malonate and 3-NP.

    “Oral administration of CoQ10 exerts significant neuroprotective effects against striatal lesions in rats produced by aminoxyacetic acid, and the mitochondrial toxins malonate and 3-NP148-150.”

    From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [148]

  • Oral CoQ10 produced dose-dependent neuroprotective effects against malonate-induced striatal lesions, depletion of ATP and increases in lactate concentration.

    “Oral administration of CoQ10 produced dose-dependent neuroprotective effects against malonate induced striatal lesions, depletion of ATP and increases in lactate concentration148.”

    From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [148]

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Authors
Beal, M. F., Henshaw, D. R., Jenkins, B. G., Rosen, B. R., & Schulz, J. B.
Affiliations
  • Massachusetts General Hospital (US)
  • Harvard University (US)
Corresponding author
Beal, M. Flint
Venue
Annals of Neurology
Publisher
Wiley
Published
1994-12
Volume
36
Issue
6
Pages
882-888
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
OpenAlex
W1965876571
Cited by
189
References
35
Citations by year
2026: 1 · 2024: 5 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 2 · 2013: 2 · 2012: 6
FWCI
2.78
Type
journal article
Language
en
Open access
closed
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5p01ns031579-05)
  • U.S. Public Health Service (16367)
  • National Institute of Neurological Disorders and Stroke (NS10828, NS31579)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
Keywords
coenzyme Q10, nicotinamide, malonate, mitochondrial toxins, striatal lesions, excitotoxicity, neuroprotection, mitochondrial bioenergetics, electron transport inhibition, complex II inhibition, ATP depletion, lactate, mitochondrial encephalopathy, neurodegenerative diseases
MeSH terms
Animals, Coenzymes, Corpus Striatum, Dose-Response Relationship, Drug, Magnetic Resonance Imaging, Male, Malonates, Mitochondria, Niacinamide, Ubiquinone, Rats, Sprague-Dawley, Rats

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