Advisor(s)

Samuel Gatley

Contributor(s)

Richard I. Duclos Jr., Ban-An Khaw

Date of Award

2010

Date Accepted

8-2010

Degree Grantor

Northeastern University

Degree Level

M.S.

Degree Name

Master of Science

Department or Academic Unit

Bouve College of Health Sciences. Department of Pharmaceutical Sciences

Keywords

pharmaceutical sciences, mice, mouse brain, [1-14C]ethanol, [2-14C]ethanol

Subject Categories

Medical sciences, Ethanol, Metabolism, Krebs cycle, Alcohol--Toxicology

Disciplines

Pharmacology, Toxicology and Environmental Health

Abstract

The objective of this thesis research is to study the distribution and metabolism of ethanol in the brain using radiolabeled ethanol. This can explain toxicological, pharmacokinetic and pharmacodynamic aspects of alcohol. The brain distribution patterns of [1-14C]ethanol and [2-14C]ethanol treated mice were found different which indicates the differences in the Krebs cycle activity in different brain regions. Earlier studies had shown differences in radioactivity distribution patterns between mice treated with [1-14C]acetaldehyde and mice treated with [1-14C]ethanol. However, the distribution patterns were observed similar in mice pretreated with disulfiram and in control mice. Moreover, hippocampus of mice treated with 100 mg/kg of disulfiram followed by [1-14C]ethanol had significantly higher amount of radioactivity compared to control mice; but the other regions had not markedly different amount of total injected radioactivity. Although, disulfiram caused behavioral changes in mice, it seemed that disulfiram did not effectively inhibit aldehyde dehydrogenase in the brain in vivo. This result was validated by measuring the total, volatile and nonvolatile radioactivity in mouse brain homogenate. The total radioactivity increased significantly, after 5 minutes of [1-14C]ethanol treatment, in the whole brain homogenate of mice treated with disulfiram followed by [1-14C]ethanol compared to control mice. However, this was not true after 2 minutes of treatment. Furthermore, in comparison with control mice, the total radioactivity in the whole brain homogenate did not increase significantly in mice pretreated with pharmacological dose of ethanol and disulfiram followed by [1-14C]ethanol. This shows that disulfiram, or possibly its active metabolite S-methyl-N,N-diethyldithiocarbamate (MeDDC), does not achieve a sufficiently high concentration in brain to inhibit aldehyde dehydrogenase.

Document Type

Master's Thesis

Rights Information

copyright 2010

Rights Holder

Dipankumar C. Patel


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