QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.103630v1 319/2/543    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jung, M. E. Articles by Simpkins, J. W. Search for Related Content PubMed PubMed Citation Articles by Jung, M. E. Articles by Simpkins, J. W. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ESTRONE ETHANOL MALONALDEHYDE

NEUROPHARMACOLOGY

A Nonfeminizing Estrogen Analog Protects against Ethanol Withdrawal Toxicity in Immortalized Hippocampal Cells

Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas

We have shown that 17-estradiol protects against ethanol withdrawal toxicity in rats. Here, we investigated whether a cellular model of ethanol withdrawal could be developed in a cultured hippocampal cell line (HT22) and whether an adamantyl-containing nonfeminizing estrogen analog, ZYC26 [(3-hydroxy-2-adamantyl(1)-4-methyl-estra-1,3,5(10)-17-one], protects against ethanol withdrawal toxicity. HT22 cells were exposed to ethanol (0–500 mM) for 24 h in the presence or absence of ZYC26 or 17-estradiol. The ethanol solution was then removed from the cells for 4 h to create ethanol withdrawal. Samples were collected at the end of a 24-h ethanol exposure or at 4 h of ethanol withdrawal to assess cell viability using a calcein assay, lipid peroxidation by measuring malondialdehyde, and protein oxidation by measuring carbonyl contents. When tested, ethanol concentrations were constantly maintained during a 24-h ethanol exposure and eliminated at 4 h of ethanol withdrawal. Ethanol withdrawal decreased cell viability and increased the levels of malondialdehyde and carbonyls more than ethanol exposure. ZYC26 reduced the cell death and malondialdehyde levels at a lower dose (1 µM) than 17-estradiol (10 µM). The increased carbonyl contents were reduced only by ZYC26 treatment. These data suggest that ethanol withdrawal can be created in HT22 cells in a manner that is more toxic than ethanol exposure and that ZYC26 is a more potent cytoprotectant than 17-estradiol against cell death and oxidative damage induced by ethanol withdrawal. Therefore, ZYC26 can be a potential alternative estrogen therapy for a cellular and oxidative imbalance associated with ethanol withdrawal.

Address correspondence to: Dr. Marianna E. Jung, Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107. E-mail: mjung{at}hsc.unt.edu

This article has been cited by other articles:

				M. E. Jung, A. M. Wilson, X. Ju, Y. Wen, D. B. Metzger, and J. W. Simpkins Ethanol Withdrawal Provokes Opening of the Mitochondrial Membrane Permeability Transition Pore in an Estrogen-Preventable Manner J. Pharmacol. Exp. Ther., March 1, 2009; 328(3): 692 - 698. [Abstract] [Full Text] [PDF]

				J. W. Simpkins, E. Perez, Xiaofei Wang, ShaoHua Yang, Yi Wen, and M. Singh The Potential for Estrogens in Preventing Alzheimer's Disease. Therapeutic Advances in Neurological Disorders, January 1, 2009; 2(1): 31 - 49. [Abstract] [PDF]