The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
In the citing paper
“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]
Citations
Cites
Morris, R. G. M., Anderson, E., Lynch, G. S., & Baudry, M. (1986) · Nature · doi:10.1038/319774a0 · Cited by 3,640
Fluorometric assay of proteins in the nanogram range
Böhlen, P., Stein, S., Dairman, W. M., & Udenfriend, S. (1973) · Archives of Biochemistry and Biophysics · doi:10.1016/s0003-9861(73)80023-2 · Cited by 1,632
Nitric Oxide Activation of Poly(ADP-Ribose) Synthetase in Neurotoxicity
Zhang, J., Dawson, V. L., Dawson, T. M., & Snyder, S. H. (1994) · Science · doi:10.1126/science.8080500 · Cited by 1,118
Beal, M. F., Brouillet, E., Jenkins, B. G., Ferrante, R. J., Kowall, N. W., Miller, J., Storey, E., Srivastava, R., Rosen, B. R., & Hyman, B. T. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-10-04181.1993 · Cited by 1,026
Self-citationBeal, M. F. (1992) · Annals of Neurology · doi:10.1002/ana.410310202 · Cited by 962
Self-citationNovelli, A., Reilly, J. A., Lysko, P. G., & Henneberry, R. C. (1988) · Brain Research · doi:10.1016/0006-8993(88)90765-2 · Cited by 961
Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations.
Frei, B. B., Kim, M. C., & Ames, B. N. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.12.4879 · Cited by 623
Alternative excitotoxic hypotheses
Albin, R. L., & Greenamyre, J. T. (1992) · Neurology · doi:10.1212/wnl.42.4.733 · Cited by 574
Frahm, J., Bruhn, H., Gyngell, M. L., Merboldt, K. D., Hänicke, W., & Sauter, R. (1989) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910110105 · Cited by 522
Shoffner, J. M., Lott, M. T., Voljavec, A. S., Soueidan, S. A., Costigan, D. A., & Wallace, D. C. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.20.7952 · Cited by 507
Schraufstätter, I. U., Hyslop, P. A., Hinshaw, D. B., Spragg, R. G., Sklar, L. A., & Cochrane, C. G. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.13.4908 · Cited by 459
Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid
Brouillet, E., Jenkins, B. G., Hyman, B. T., Ferrante, R. J., Kowall, N. W., Srivastava, R., Roy, D. S., Rosen, B. R., & Beal, M. F. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb05859.x · Cited by 367
Self-citationInvolvement of Free Radicals in Excitotoxicity In Vivo
Schulz, J. B., Henshaw, D. R., Siwek, D. F., Jenkins, B. G., Ferrante, R. J., Cipolloni, P. B., Kowall, N. W., Rosen, B. R., & Beal, M. F. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.64052239.x · Cited by 322
Self-citationBeal, M. F., Brouillet, E., Jenkins, B. G., Henshaw, R., Rosen, B. R., & Hyman, B. T. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03633.x · Cited by 297
Self-citationGreene, J. G., Porter, R. H. P., Eller, R. V., & Greenamyre, J. T. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03634.x · Cited by 208
Koek, W., & Colpaert, F. C. (1990) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)13353-3 · Cited by 202
Storey, E., Hyman, B. T., Jenkins, B. G., Brouillet, E., Miller, J. M., Rosen, B. R., & Beal, M. F. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb10080.x · Cited by 164
Self-citationThe enzymatic measurement of adenine nucleotides and P-creatine in picomole amounts
Lust, W. D., Feussner, G. K., Barbehenn, E. K., & Passonneau, J. V. (1981) · Analytical Biochemistry · doi:10.1016/0003-2697(81)90144-5 · Cited by 163
Ihara, Y., Namba, R., Kuroda, S., SATO, T. A., & Shirabe, T. (1989) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(89)90112-3 · Cited by 161
Coenzyme Q 10 with multiple vitamins is generally ineffective in treatment of mitochondrial disease
Matthews, P. M., Ford, B., Dandurand, R. J., Eidelman, D. H., O'Connor, D., Sherwin, A. L., Karpati, G., Andermann, F., & Arnold, D. L. (1993) · Neurology · doi:10.1212/wnl.43.5.884 · Cited by 125
MELAS syndrome with mitochondrial tRNA Leu[UUR] mutation
Penn, A. M. W., Lee, J. W. K., Thuillier, P., Wagner, M., Maclure, K. M., Menard, M. R., Hall, L. D., & Kennaway, N. G. (1992) · Neurology · doi:10.1212/wnl.42.11.2147 · Cited by 124
Aminooxyacetic Acid Results in Excitotoxin Lesions by a Novel Indirect Mechanism
Beal, M. F., Swartz, K. J., Hyman, B. T., Storey, E., Finn, S. F., & Koroshetz, W. J. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb08258.x · Cited by 118
Self-citationSchneider, H., Lemasters, J. J., & Hackenbrock, C. R. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)33893-6 · Cited by 110
Clinical and biochemical correlations in mitochondrial myopathies treated with coenzyme Q 10
Bresolin, N., Bet, L., Binda, A., Moggio, M. G., Comi, G. P., Nador, F., Ferrante, C., Carenzi, A., & Scarlato, G. (1988) · Neurology · doi:10.1212/wnl.38.6.892 · Cited by 107
Vatassery, G. T., Brin, M. F., Fahn, S., Kayden, H. J., & Traber, M. G. (1988) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1988.tb01083.x · Cited by 106
Therapy of mitochondrial disorders
Przyrembel, H. (1987) · Journal of Inherited Metabolic Disease · doi:10.1007/bf01812853 · Cited by 102
Nishikawa, Y., Takahashi, M. M., Yorifuji, S., Nakamura, Y., Ueno, S., Tarui, S., Kozuka, T., & Nishimura, T. (1989) · Neurology · doi:10.1212/wnl.39.3.399 · Cited by 100
Ubiquinone Protects Cultured Neurons against Spontaneous and Excitotoxin-Induced Degeneration
Favit, A., Nicoletti, F., Scapagnini, U., & Canonico, P. L. (1992) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1992.88 · Cited by 98
Treatment of complex I deficiency with riboflavin
Bernsen, P. L. J. A., Gabreëls, F. J. M., Ruitenbeek, W., & Hamburger, H. (1993) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(93)90108-b · Cited by 97
Malonate produces striatal lesions by indirect NMDA receptor activation
Henshaw, R., Jenkins, B. G., Schulz, J. B., Ferrante, R. J., Kowall, N. W., Rosen, B. R., & Beal, M. F. (1994) · Brain Research · doi:10.1016/0006-8993(94)91412-5 · Cited by 92
Self-citationAbe, K., Fujimura, H., Nishikawa, Y., Yorifuji, S., Mezaki, T., Hirono, N., Nishitani, N., & Kameyama, M. (1991) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1991.tb03962.x · Cited by 76
A protective effect of coenzyme Q10 on ischemia and reperfusion of the isolated perfused rat heart
Ohhara, H. (1981) · Journal of Molecular and Cellular Cardiology · doi:10.1016/0022-2828(81)90229-7 · Cited by 74
Reahal, S., & Wrigglesworth, J. M. (1992) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)08606-4 · Cited by 57
Shew, R. L., Robinson, M. F., Olansky, L., Yee, J. A., Titishov, N., Mechoulam, R., Zimmerman, A. M., Raghoebar, M., Tiemessen, H. L. G. M., van den Berg, W. B., et al. (2008) · Pharmacology · doi:10.1159/000138630 · Cited by 18
Invalidity of the Rao Map Function for Three Loci
Weeks, D. E. (1994) · Human Heredity · doi:10.1159/000154213 · Cited by 12
Research works printed but not linked: 6
- Beal K, 1993, Both local and systemic administration of the mitochondrial toxin sodium azide result in striatal lesions by an excitotoxic mechanism, Neurology, 43, A407
- Nakamura K, 1989, Biochemical and clinical aspects of coenzyme Q10, 3
- OkamotoK KobayashiK TakahashiK et al.Biochemical roles of coenzyme Q on cultured ventricular myocytes: effects of coenzyme Q on mitochondrial ATP productionPresented at the 8th international coenzyme Q symposium Stockholm Sweden Nov 11 1993
- Barbiroli K, 1994, Improved brain and muscle energy metabolism in patients with mitochondrial cytopathies treated with coenzyme, Q. Neurology, 44, A404
- Heb K, 1993, Proceedings of Society of Magnetic Resonance Medicine 12th annual meeting, 1557
- Koroshetz K, 1993, Ubiquinone lowers occipital lactate levels in patients with Huntington's disease, Neurology, 43, A334
Cited by
Sorted by citations
Aging, energy, and oxidative stress in neurodegenerative diseases
Beal, M. F. (1995) · Annals of Neurology · doi:10.1002/ana.410380304 · Cited by 1,434
Self-citationGilgun‐Sherki, Y., Melamed, E., & Offen, D. (2001) · Neuropharmacology · doi:10.1016/s0028-3908(01)00019-3 · Cited by 850
Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanism
Golomb, B. A., & Evans, M. A. (2008) · American Journal of Cardiovascular Drugs · doi:10.2165/0129784-200808060-00004 · Cited by 677
Matthews, R. T., Yang, L., Browne, S., Baik, M., & Beal, M. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.15.8892 · Cited by 557
Self-citationMitochondria, Oxidative Damage, and Inflammation in Parkinson's Disease
Beal, M. F. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb07470.x · Cited by 529
Self-citation
Metadata
- 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
- ORCID
- Rosen, Bruce R.
- 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 › Neuroprotection in Cerebral Ischemia
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
