Cited by 216Alzheimer's disease research and treatmentsRedox biology and oxidative stressAntioxidant Activity and Oxidative Stress

beta-Amyloid toxicity in organotypic hippocampal cultures: Protection by EUK-8, a synthetic catalytic free radical scavenger

Open access
Bruce, A J, Malfroy, B, Baudry, M·1996·Proceedings of the National Academy of Sciences

Abstract

Oxygen free radicals have been proposed to mediate amyloid peptide (beta-AP)-induced neurotoxicity. To test this hypothesis, we evaluated the effects of EUK-8, a synthetic catalytic superoxide and hydrogen peroxide scavenger, on neuronal injury produced by beta-AP in organotypic hippocampal slice cultures. Cultures of equivalent postnatal day 35 (defined as mature) and 14 (defined as immature) were exposed to various concentrations of beta-AP (1-42 or 1-40) in the absence or presence of 25 microM EUK-8 for up to 72 hours. Neuronal injury was assessed by lactate dehydrogenase release and semiquantitative analysis of propidium iodide uptake at various times after the initiation of beta-AP exposure. Free radical production was inferred from the relative increase in dichlorofluorescein fluorescence, and the degree of lipid peroxidation was determined by assaying thiobarbituric acid-reactive substances. Treatment of mature cultures with beta-AP (50-250 microg/ml) in serum-free conditions resulted in a reproducible pattern of damage, causing a time-dependent increase in neuronal injury accompanied with formation of reactive oxygen species. However, immature cultures were entirely resistant to beta-AP-induced neurotoxicity and also demonstrated no dichlorofluorescein fluorescence or increased lipid peroxidation after beta-AP treatment. Moreover, mature slices exposed to beta-AP in the presence of 25 microM EUK-8 were significantly protected from beta-AP-induced neurotoxicity. EUK-8 also completely blocked beta-AP-induced free radical accumulation and lipid peroxidation. These results not only support a role for oxygen free radicals in beta-AP toxicity but also highlight the therapeutic potential of synthetic radical scavengers in Alzheimer disease.

Integrity signals

Registry

Crossref · 10.1073/pnas.93.6.2312

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

The text we found for this paper looks like another document, so its claims and self-check weren’t run. The registry and citation checks still apply.

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The text we found for this paper looks like another document, so the self-check wasn’t run.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Goodman Y., Steiner M. R., Steiner S. M., Mattson M. P. Nordihydroguaiaretic acid protects hippocampal neurons against amyloid beta-peptide toxicity, and attenuates free radical and calcium accumulation. Brain Res. 1994 Aug 15;654(1):171–176. doi: 10.1016/0006-8993(94)91586-5. [DOI] [PubMed] [Google Scholar] · DOI

Cited by

Sorted by citations

Authors
Bruce, A. J., Malfroy, B., & Baudry, M.
Affiliations
  • Neuroscience Program, University of Southern California, Los Angeles 90089-2520, USA.
  • University of Southern California (US)
Venue
Proceedings of the National Academy of Sciences
Published
1996-03-19
Volume
93
Issue
6
Pages
2312-2316
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2132787891
Cited by
216
References
44
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 5 · 2018: 1 · 2017: 5 · 2016: 8 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 6
FWCI
9.44
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
amyloid-beta, neurotoxicity, superoxide scavengers, oxygen free radicals, reactive oxygen species, lipid peroxidation, hippocampal slice cultures, neuronal injury, Alzheimer's disease
MeSH terms
Animals, Biological Transport, Cell Membrane Permeability, Ethylenediamines, Hippocampus, L-Lactate Dehydrogenase, Organometallic Compounds, Oxidation-Reduction, Propidium, Free Radical Scavengers, Amyloid beta-Protein Precursor, Rats, Sprague-Dawley, Reactive Oxygen Species, Culture Techniques, 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