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Cited by 66Effects and risks of endocrine disrupting chemicalsAlzheimer's disease research and treatmentsAntioxidant Activity and Oxidative Stress

Effects of bisphenol A on oxidative stress in the rat brain

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Kobayashi, Keiko, Liu, Yanchen, Ichikawa, Hiroshi, Takemura, Shigekazu, Minamiyama, Yukiko·2020·Antioxidants
DOI 10.3390/antiox9030240PMC PMC7139612
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Abstract

We investigated the effect of bisphenol A (BPA) on oxidative stress and tau-related proteins in adult rat brains. BPA (10 mg/L) was administered to rats for eight weeks through their drinking water. The reactive oxygen species (ROS) scavenging capacity for hydroxyl radicals in the plasma was reduced after two weeks. In the hippocampus, four and eight weeks of BPA increased the ratio of oxidized DJ-1/DJ-1 (PARK7). The ratio of phosphorylated-GSK3β/GSK3β and phosphorylated-AKT/AKT increased after one week of BPA treatment. The ratio of phosphorylated JNK/JNK and phosphorylated-ERK/ERK increased after eight weeks of BPA; the elevation could be related to tau phosphorylation. Protein phosphatase 2A (PP2A) in the hippocampus decreased after eight weeks of BPA treatment. At that time, SOD1 was significantly induced, but no changes in SOD2 expression were apparent in the hippocampus. Furthermore, the ratio of phosphorylated-tau (PHF-1, Ser396/ Ser404) to total tau level did not change. However, PHF-1 or other sites of tau could be phosphorylated after eight weeks in the hippocampi of rats. BPA induced systemic oxidative stress and could change ROS-induced signaling pathways in the brain. These results suggest that mitochondrial dysfunction possibly is not responsible for oxidative stress and neurodegeneration due to low doses of BPA.

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  • BPA and related compounds increase ROS production, promoting neuronal damage and apoptosis.

    “BPA and related compounds increase ROS production, thereby promoting neuronal damage and apoptosis (Kobayashi et al., 2020; Shen et al., 2023).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Kobayashi et al., 2020

    The Introduction says BPA increases ROS, and the Discussion reports BPA-induced oxidative stress in rat brains. The Discussion describes neuronal loss as a possible consequence of ROS, not an observed outcome of this study; it also reports no increase in the apoptosis marker caspase 9 in the treated hippocampus. The paper does not establish the claim for related compounds. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Kobayashi, K., Liu, Y., Ichikawa, H., Takemura, S., & Minamiyama, Y.
Affiliations
  • Kyoto Prefectural University (JP)
  • Doshisha University (JP)
  • Osaka City University (JP)
Corresponding author
Minamiyama, Yukiko
ORCID
Venue
Antioxidants
Publisher
MDPI AG
Published
2020-03-16
Volume
9
Issue
3
Pages
240
ISSN
2076-3921 (ISSN-L)
DOI
10.3390/antiox9030240
PMC
PMC7139612
OpenAlex
W3010858630
Cited by
66
References
1
Citations by year
2026: 9 · 2025: 12 · 2024: 9 · 2023: 14 · 2022: 9 · 2021: 9 · 2020: 4
FWCI
3.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Antioxidants (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Japan Society for the Promotion of Science (18K08654)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
bisphenol A, oxidative stress, tau phosphorylation, reactive oxygen species, DJ-1, GSK3β, Akt, JNK, ERK, protein phosphatase 2A, SOD1, manganese superoxide dismutase, hippocampus, neurodegeneration, mitochondrial dysfunction, neurotoxicity

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