Induction of brain CYP2E1 by chronic ethanol treatment and related oxidative stress in hippocampus, cerebellum, and brainstem
Abstract
Ethanol is one of the most commonly abused substances, and oxidative stress is an important causative factor in ethanol-induced neurotoxicity. Cytochrome P450 2E1 (CYP2E1) is involved in ethanol metabolism in the brain. This study investigates the role of brain CYP2E1 in the susceptibility of certain brain regions to ethanol neurotoxicity. Male Wistar rats were intragastrically treated with ethanol (3.0 g/kg, 30 days). CYP2E1 protein, mRNA expression, and catalytic activity in various brain regions were respectively assessed by immunoblotting, quantitative quantum dot immunohistochemistry, real-time RT-PCR, and LC-MS. The generation of reactive oxygen species (ROS) was analyzed using a laser confocal scanning microscope. The hippocampus, cerebellum, and brainstem were selectively damaged after ethanol treatment, indicated by both lactate dehydrogenase (LDH) activity and histopathological analysis. Ethanol markedly increased the levels of CYP2E1 protein, mRNA expression, and activity in the hippocampus and cerebellum. CYP2E1 protein and activity were significantly increased by ethanol in the brainstem, with no change in mRNA expression. ROS levels induced by ethanol paralleled the enhanced CYP2E1 proteins in the hippocampus, granular layer and white matter of cerebellum as well as brainstem. Brain CYP2E1 activity was positively correlated with the damage to the hippocampus, cerebellum, and brainstem. These results suggest that the selective sensitivity of brain regions to ethanol neurodegeneration may be attributed to the regional and cellular-specific induction of CYP2E1 by ethanol. The inhibition of CYP2E1 levels may attenuate ethanol-induced oxidative stress via ROS generation.
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The role of CYP2E1 in brain ethanol metabolism and its association with alcohol-mediated oxidative neuronal injury and aging-related AD and PD have been suggested.
“The role of CYP2E1 in brain ethanol metabolism and its association with alcohol-mediated oxidative neuronal injury155–160 and aging-related AD and PD161 have also been suggested.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [159]
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- Authors
- Zhong, Y., Dong, G., Luo, H., Cao, J., Wang, C., Wu, J., Feng, Y.-Q., & Yue, J.
- Affiliations
- Wuhan University (CN)
- Inner Mongolia University of Science and Technology (CN)
- Corresponding author
- Yue, Jiang
- Venue
- Toxicology
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 302
- Issue
- 2-3
- Pages
- 275-284
- ISSN
- 0300-483X (ISSN-L)
- OpenAlex
- W1976538303
- Cited by
- 77
- References
- 54
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 10 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 10 · 2016: 5 · 2015: 8 · 2014: 7 · 2013: 3
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30960334, 30973582, 30600773)
- Program for New Century Excellent Talents in University
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- CYP2E1, chronic ethanol exposure, ethanol neurotoxicity, oxidative stress, reactive oxygen species, hippocampus, cerebellum, brainstem, CYP2E1 induction, lactate dehydrogenase activity, brain damage
- MeSH terms
- Ethanol, Animals, Brain Stem, Cerebellum, Chlorzoxazone, Hippocampus, Humans, L-Lactate Dehydrogenase, Male, Neuroblastoma, RNA, Messenger, Up-Regulation, Rats, Wistar, Reactive Oxygen Species, Oxidative Stress, Microscopy, Confocal, Cytochrome P-450 CYP2E1, Cell Line, Tumor, Rats, Real-Time Polymerase Chain Reaction, Cytochrome P-450 CYP2E1 Inhibitors
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