Ethanol‐Induced Oxygen Radical Formation and Lipid Peroxidation in Rat Brain: Effect of Chronic Alcohol Consumption
Abstract
Abstract: The effect of chronic and in vitro ethanol exposure on brain oxygen radical formation and lipid peroxidation was analyzed. Ethanol induces a dose‐dependent increase in lipid peroxidation in brain homogenates. The peroxidative effects of alcohol seem to be related to both cytochrome P450 and the ethanol‐inducible form of cytochrome P450 (CYP2E1), because preincubation with metyrapone (an inhibitor of cytochrome P450) or with an antibody against CYP2E1 abolished the ethanol‐increased lipid peroxidation. Using the formation of dichlorofluorescein, we also demonstrated that both in vitro and chronic alcohol exposure significantly enhanced the formation of oxygen radical species in synaptosomes. Chronic alcohol treatment also leads to an induction of cytochrome P450 (230%), NADPH cytochrome c reductase (180%), NADPH oxidation (184%), and CYP2E1 in brain microsomes. In addition, this treatment produced a decrease in the GSH/GSSG ratio in brain and significantly enhanced the levels of superoxide dismutase and catalase activities. This mechanism could be involved in the toxic effects of ethanol on brain and membrane alterations occurring after chronic ethanol intake.
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CYP2E1 is widely expressed throughout the brain, such as in the cerebral cortex, hippocampus, and cerebellum; brain CYP2E1 is inducible by ethanol and may play a key role in cerebral ethanol metabolism, especially after chronic and/or binge alcohol intake.
“In contrast, CYP2E1 is widely expressed throughout the brain, such as in the cerebral cortex, hippocampus, and cerebellum.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [155]
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 [155]
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Ezquer, F. E., Morales, P., Quintanilla, M. E., Santapau, D., Lespay‐Rebolledo, C., Ezquer, M., Herrera‐Marschitz, M., & Israel, Y. (2018) · Scientific Reports · doi:10.1038/s41598-018-22750-7 · Cited by 46 · see citing works
Heaton, M. B., Paiva, M., & Siler‐Marsiglio, K. I. (2011) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01445.x · Cited by 45 · see citing works
“Ethanol enhances generation of destructive reactive oxygen species (ROS), often with concomitant reductions in the expression or activity of protective endogenous antioxidants (Uysal et al., 1989; Davis et al., 1990; Montoliu et al., 1994; Henderson et al., 1995; Kotch et al., 1995; Reddy et al., 1999; Heaton et al.,…”
BackgroundRegional and cellular distribution of CYP2E1 in monkey brain and its induction by chronic nicotine
Joshi, M., & Tyndale, R. F. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.11.001 · Cited by 46 · see citing works
Paraquat-Induced Free Radical Reaction in Mouse Brain Microsomes
Yang, W., & Sun, A. Y. (1998) · Neurochemical Research · doi:10.1023/a:1022497319548 · Cited by 45 · see citing works
“In view of the finding that cytochrome P450 enzyme was present in the brain (40-41), mouse brain microsomes were used to evaluate the ability of paraquat to induce lipid peroxidation.”
MethodShahabi, H. N., Andersson, D. R., & Nissbrandt, H. (2008) · Synapse · doi:10.1002/syn.20505 · Cited by 44 · see citing works
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Roles of Oxidative Stress and Autophagy in Alcohol-Mediated Brain Damage
Ruiter-Lopez, L., Khan, M. A. S., Wang, X., & Song, B. (2025) · Antioxidants · doi:10.3390/antiox14030302 · Cited by 45 · see citing works
“However, it is important to consider the potential impacts of the elevated CYP2E1 on the oxidative cell and brain injury, since CYP2E1 was shown to be induced by 17.5 mM ethanol in primary neuronal cells [61], primary astrocytes [62], and rodent brains after chronic alcohol exposures [63–66].”
InfluentialImmune function genes, genetics, and the neurobiology of addiction
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Israel, Y., Quintanilla, M. E., Ezquer, F. E., Morales, P., Santapau, D., Berríos‐Cárcamo, P., Ezquer, M., Olivares, B., & Herrera‐Marschitz, M. (2019) · Addiction Biology · doi:10.1111/adb.12853 · Cited by 41 · see citing works
Alpha-lipoic acid prevents ethanol-induced protein oxidation in mouse hippocampal HT22 cells
Pirlich, M., Kiok, K., Sandig, G., et al. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00415-9 · Cited by 41 · see citing works
Ethanol Induced Changes in Superoxide Anion and Nitric Oxide in Cultured Microglia
Colton, C. A., Snell‐Callanan, J., & Chernyshev, O. N. (1998) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1998.tb04315.x · Cited by 41 · see citing works
Changes in some pro-and antioxidants in rat cerebellum after chronic alcohol intake
Rouach, H., Houzé, P., Gentil, M., Orfanelli, M.-T., & Nordmann, R. (1997) · Biochemical Pharmacology · doi:10.1016/s0006-2952(96)00770-8 · Cited by 40 · see citing works
Raso, G. M., Simeoli, R., Russo, R., Santoro, A. N., Pirozzi, C., Bianca, R. D. D. V., Mitidieri, E., Paciello, O., Pagano, T. B., Orefice, N. S., et al. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2013.07.007 · Cited by 40 · see citing works
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Guéguen, S., Pirollet, P., Leroy, P., Guilland, J.-C., Arnaud, J., Paillé, F., Siest, G., Visvikis‐Siest, S., Herçberg, S., & Herbeth, B. (2003) · Journal of the American College of Nutrition · doi:10.1080/07315724.2003.10719308 · Cited by 41 · see citing works
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“It appears that ethanol-induced neurotoxicity is mediated by oxidative stress and mitochondrial malfunction [11, 13, 25].”
Background
- Authors
- Montoliu, C., Vallés, S., Renau‐Piqueras, J., & Guerri, C.
- Affiliations
- Instituto de Investigación Sanitaria La Fe (ES)
- Corresponding author
- Guerri, Consuelo
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1994-11
- Volume
- 63
- Issue
- 5
- Pages
- 1855-1862
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1978987336
- Cited by
- 269
- References
- 0
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 1 · 2019: 7 · 2018: 10 · 2017: 6 · 2016: 9 · 2015: 10 · 2014: 10 · 2013: 5 · 2012: 13
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- chronic alcohol consumption, oxygen free radicals, lipid peroxidation, brain, cytochrome P450, CYP2E1, metyrapone, dichlorofluorescein, synaptosomes, NADPH-cytochrome c reductase, NADPH oxidation, glutathione, superoxide dismutase, catalase, ethanol neurotoxicity, brain microsomes
- MeSH terms
- Ethanol, Alcoholism, Animals, Brain, Brain Chemistry, Catalase, Cytochrome P-450 Enzyme System, Dose-Response Relationship, Drug, Electrophoresis, Polyacrylamide Gel, Female, Free Radicals, Glutathione, Isomerism, NADP, Oxygen, Superoxide Dismutase, Synaptosomes, Immunoblotting, Lipid Peroxidation, Rats, Wistar, Reactive Oxygen Species, Glutathione Disulfide, Rats
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