Induction of brain cytochrome P-450IIE1 by chronic ethanol treatmen
Abstract
Cytochrome P-450 mediated metabolism is potentially involved in the expression of the pharmacological and/or toxicological effects of a wide variety of drugs and environmental chemicals upon tissues which contain this metabolic system. In the present investigation, the presence of cytochrome P-450IIE1 and associated mono-oxygenase activities in brain and the effect of chronic ethanol treatment on brain cytochrome P-450 (P-450) were studied. Aniline hydroxylase, N-nitroso-dimethylamine N-demethylase and p-nitrophenol hydroxylase activities (known to be mediated by P-450IIE1) were detectable in brain microsomes from untreated rats and were about 5%, 125% and 8.3%, respectively, of the corresponding hepatic levels. Chronic ethanol treatment resulted in induction of the above enzyme activities in brain microsomes by 243%, 496% and 155%, respectively. Intake of ethanol for a prolonged period also resulted in the induction of total P-450 in the brain (150% of the control). Addition of the antisera raised against rat liver cytochrome P-450IIE1 markedly inhibited brain microsomal p-nitrophenol hydroxylase activity. Immunoblot analysis of rat brain microsomes using the above antisera also revealed the induction of brain cytochrome P-450IIE1 following chronic ethanol administration. Immunocytochemical localization of cytochrome P-450IIE1 using the above antisera, revealed the preferential localization of the enzyme in the neuronal cell bodies in the cortex, hippocampus, basal ganglia, hypothalamic nuclei and reticular nuclei in the brainstem of rats treated chronically with ethanol. Based upon these studies, it is conceivable that chronic alcohol ingestion could enhance the sensitivity of certain regions of the brain to environmental chemicals that are metabolized to more toxic derivatives by the P-450 system.
Integrity signals
Registry
Cites
Statistics
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?
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 [154]
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Towbin, H., Staehelin, T., & Gordon, J. (1979) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.76.9.4350 · Cited by 51,421 · see citing works
Colowick, S. P., Joshi, M. D., Jagannathan, & KAPLAN, N. O. (1966) · Cited by 26,137 · see citing works
Maturation of the head of bacteriophage T4
Laemmli, U. K., & Fãvre, M. (1973) · Journal of Molecular Biology · doi:10.1016/0022-2836(73)90198-8 · Cited by 3,725 · see citing works
Psychopharmacology: The third generation of progress
O’Connell, R. A. (1988) · Comprehensive Psychiatry · doi:10.1016/0010-440x(88)90057-0 · Cited by 3,020 · see citing works
Cytochrome P-450: Structure, Mechanism, and Biochemistry
de Montellano, O., & Paul, R. (1986) · Medical Entomology and Zoology · Cited by 2,667 · see citing works
Phillips, A. H., & LANGDON, R. G. (1962) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)73803-4 · Cited by 1,433 · see citing works
Principles and Methods of Toxicology
(1984) · Food and Chemical Toxicology · doi:10.1016/0278-6915(84)90066-8 · Cited by 1,423 · see citing works
Evidence for Biochemically Different Types of Vesicles in the Hepatic Microsomal Fraction*
Imai, Y., Ito, A., & Sato, R. (1966) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a128453 · Cited by 749 · see citing works
Bernard, Testa, M., Meyer, U., & Testa, B. (1964) · Academic Press eBooks · Cited by 609 · see citing works
Charness, M. E. (1993) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1993.tb00718.x · Cited by 536 · see citing works
p-Nitrophenol hydroxylation. A microsomal oxidation which is highly inducible by ethanol.
Reinke, L. A., & Moyer, M. J. (1985) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)08248-0 · Cited by 416 · see citing works
Song, B., Gelboin, H. V., Park, S. S., Yang, C. S., & Gonzalez, F. J. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)66620-7 · Cited by 405 · see citing works
Self-citationNeuronal Loss in Hippocampus Induced by Prolonged Ethanol Consumption in Rats
Walker, D. W., Barnes, D. E., Zornetzer, S. F., Hunter, B. E., & Kubanis, P. (1980) · Science · doi:10.1126/science.7394532 · Cited by 394 · see citing works
Quantitative determination of cytochrome P-450 in rat liver homogenate
Matsubara, T., Koike, M., Touchi, A., Tochino, Y., & SUGENO, K. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90114-7 · Cited by 358 · see citing works
TORVIK, A., Lindboe, C. F., & Rogde, S. (1982) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(82)90145-9 · Cited by 342 · see citing works
Characterization of a major form of rat hepatic microsomal cytochrome P-450 induced by isoniazid.
Ryan, D. E., Ramanathan, L., Iida, S., et al. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)88984-0 · Cited by 309 · see citing works
Ohnishi, K., & Lieber, C. S. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)66943-7 · Cited by 261 · see citing works
Regional distribution of ethanol-inducible cytochrome P450 IIE1 in the rat central nervous system
Hansson, T., Tindberg, N., Ingelman-Sundberg, M., & Ko¨hler, C. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90154-v · Cited by 202 · see citing works
Thomas, P. E., Bandiera, S. M., Maines, S. L., Ryan, D. E., & Levin, W. (1987) · Biochemistry · doi:10.1021/bi00382a031 · Cited by 201 · see citing works
Stabilization of Cytochrome P450j Messenger Ribonucleic Acid in the Diabetic Rat
Song, B. J., Matsunaga, T., Hardwick, J. P., Park, S. S., Veech, R. L., Yang, C. S., Gelboin, H. V., & Gonzalez, F. J. (1987) · Molecular Endocrinology · doi:10.1210/mend-1-8-542 · Cited by 200 · see citing works
Self-citationSasame, H. A., Ames, M. M., & Nelson, S. D. (1977) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(77)90510-1 · Cited by 162 · see citing works
Warner, M. N., Köhler, C., Hansson, T., & Gustafsson, J.-Α. (1988) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1988.tb10573.x · Cited by 150 · see citing works
Hypothesis: Alcoholic Liver Injury and the Covalent Binding of Acetaldehyde
Sorrell, M. F., & Tuma, D. J. (1985) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1985.tb05549.x · Cited by 135 · see citing works
Ethanol Oxidation by Rat Brain in Vivo
Cohen, G., Sinet, P. M., & Heikkila, R. E. (1980) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1980.tb04833.x · Cited by 130 · see citing works
ALCOHOL DEHYDROGENASE ACTIVITY IN RAT BRAIN AND LIVER
Raskin, N. H., & Sokoloff, L. (1970) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1970.tb11392.x · Cited by 104 · see citing works
Immunochemical evidence for a role of cytochrome P-450 in liver microsomal ethanol oxidation
Koop, D. R., Nordblom, G. D., & Coon, M. J. (1984) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(84)90272-8 · Cited by 82 · see citing works
Demethylation and denitrosation of nitrosamines by cytochrome P-450 isozymes
Tu, Y. Y., & Yang, C. S. (1985) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(85)90476-x · Cited by 71 · see citing works
Rat brain cytochromes P-450: catalytic, immunochemical properties and inducibility of multiple forms
Anandatheerthavarada, H. K., Shankar, S. K., & Ravindranath, V. (1990) · Brain Research · doi:10.1016/0006-8993(90)90047-f · Cited by 70 · see citing works
Self-citationXenobiotic metabolism in human brain — presence of cytochrome P-450 and associated mono-oxygenases
Ravindranath, V., Anandatheerthavarada, H. K., & Shankar, S. K. (1989) · Brain Research · doi:10.1016/0006-8993(89)91083-4 · Cited by 70 · see citing works
Self-citationBiochemical Pharmacology of Alcohol
Ellingboe, J., & Mendelson, J. H. (1982) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-67770-0_11 · Cited by 54 · see citing works
Cytochrome P-450 b and c in the rat brain and pituitary gland.
Näslund, B., Glaumann, H., Warner, M. N., Gustafsson, J.-Å., & Hansson, T. G. (1988) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)13099-x · Cited by 49 · see citing works
Nadph cytochrome P-450 reductase in rat, mouse and human brain
Ravindranath, V., Anandatheerthavarada, H. K., & Shankar, S. K. (1990) · Biochemical Pharmacology · doi:10.1016/0006-2952(90)90279-t · Cited by 48 · see citing works
Self-citation[58] Induction, purification, and characterization of cytochrome P450IIE
Yang, C. S., Patten, C., Ishizaki, H., et al. (1991) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(91)06129-q · Cited by 45 · see citing works
Ravindranath, V., & Varada, H. K. A. T. (1989) · Biochemical Journal · doi:10.1042/bj2610769 · Cited by 28 · see citing works
Self-citationStudies on ethanol-inducible cytochrome P-450 in rabbit liver, lungs and kidneys
Ueng, T., Friedman, F. K., Miller, H., et al. (1987) · Biochemical Pharmacology · doi:10.1016/0006-2952(87)90554-5 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Rungratanawanich, W., Qu, Y., Wang, X., Essa, M. M., & Song, B.-J. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00561-7 · Cited by 411 · see citing works
Self-citationAlcohol-induced oxidative stress in brain endothelial cells causes blood-brain barrier dysfunction
Haorah, J., Knipe, B., Leibhart, J., Ghorpade, A., & Persidsky, Y. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.0605340 · Cited by 275 · see citing works
Upadhya, S. C., Tirumalai, P. S., Boyd, M. R., Mori, T., & Ravindranath, V. (2000) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1477 · Cited by 132 · see citing works
Self-citationPutative Role of Brain Acetaldehyde in Ethanol Addiction
Deng, X.-S., & Deitrich, R. (2008) · Current Drug Abuse Reviewse · doi:10.2174/1874473710801010003 · Cited by 105 · see citing works
Expression of constitutive and inducible cytochrome P450 2E1 in rat brain
Yadav, S., Dhawan, A., Singh, R. L., Seth, P. K., & Parmar, D. (2006) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-005-9109-z · Cited by 45 · see citing works
Valencia-Olvera, A. C., Morán, J., Camacho-Carranza, R., Prospéro-García, O., & Espinosa-Aguirre, J. J. (2014) · Toxicology in Vitro · doi:10.1016/j.tiv.2014.05.014 · Cited by 36 · see citing works
Molecular targets of disulfiram action on song maturation in zebra finches
Denisenko-Nehrbass, N. I., & Mello, C. V. (2001) · Molecular Brain Research · doi:10.1016/s0169-328x(01)00002-x · Cited by 20 · see citing works
- Authors
- Anandatheerthavarada, H. K., Shankar, S. K., Bhamre, S., Boyd, M. R., Song, B.-J., & Ravindranath, V.
- Affiliations
- National Institute of Mental Health and Neurosciences (IN)
- National Institutes of Health (US)
- Corresponding author
- Ravindranath, Vijayalakshmi
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1993-01
- Volume
- 601
- Issue
- 1-2
- Pages
- 279-285
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2036977803
- Cited by
- 90
- References
- 37
- Citations by year
- 2025: 2 · 2023: 1 · 2021: 3 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 5 · 2013: 4 · 2012: 1
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- chronic ethanol exposure, brain microsomes, enzyme induction, aniline hydroxylase, p-nitrophenol hydroxylase, immunocytochemical localization, neuronal localization, brainstem, hippocampus
- MeSH terms
- Ethanol, Animals, Brain, Carbon Monoxide, Cytochrome P-450 Enzyme System, Enzyme Induction, Mixed Function Oxygenases, Immunohistochemistry, Liver, Male, Microsomes, Microsomes, Liver, Neurons, Oxidoreductases, N-Demethylating, Spectrophotometry, Ultraviolet, Blotting, Western, Rats, Wistar, Cytochrome P-450 CYP2E1, 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
