Masters Theses

Abstract

"Acetaminophen (APAP) is the most widely used pharmaceutical analgesic-antipyretic agent in the world, but its toxicity is a common cause of drug-induced hepatotoxicity. With APAP toxicity, cellular glutathione (GSH) is depleted. This results in the availability of N-acetyl-p-benzoquinone imine (NAPQI), is a toxic metabolite of APAP that binds to cellular macromolecules, which leads to cell necrosis. N-acetyl cysteine (NAC), a GSH precursor, is the only approved antidote for an acetaminophen overdose. It is a negatively charged molecule that diminishes its penetration into the cells, thereby requiring fairly high doses that increase the severity of side effects. In addition, oral and I.V. administration of NAC in a hospital setting is laborious and costly. Recently, NACA, an amide form of NAC, which is neutral at physiological pH has been developed to improve NAC's bioavailability. Therefore, in this study, we conducted an investigation to determine the mechanism of APAP-induced hepatotoxicity. We also evaluated the hepatoprotective effectiveness of NACA and compared it with NAC in the hepatic cell line, HepaRG. This comparison was based on several oxidative stress parameters, including the levels of intracellular reactive oxygen species, GSH, various antioxidant enzyme activities, and lactate dehydrogenase levels. In conclusion, NACA protected HepaRG cells against damage induced by acetaminophen toxicity and may, therefore, be a more useful antidote than NAC (the only approved antidote)"--Abstract, page iii.

Advisor(s)

Ercal, Nuran

Committee Member(s)

Kapila, Shubhender
Reddy, Prakash

Department(s)

Chemistry

Degree Name

M.S. in Chemistry

Sponsor(s)

King Abdulaziz University

Publisher

Missouri University of Science and Technology

Publication Date

Spring 2013

Pagination

xi, 54 pages

Note about bibliography

Includes bibliographical references (leaves 48-49).

Rights

© 2013 Ahdab Naeem Khayyat, All rights reserved.

Document Type

Thesis - Open Access

File Type

text

Language

English

Library of Congress Subject Headings

Acetaminophen -- Toxicology
Glutathione -- Molecular aspects
Hepatotoxicology -- Testing
Oxidative stress

Thesis Number

T 10291

Electronic OCLC #

853501607

Included in

Chemistry Commons

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