Doctoral Dissertations

Keywords and Phrases

Acetaminophen; Hepatotoxicity; N-acetylcysteine; N-acetylcysteine amide; Nephrotoxicity; Oxidative stress

Abstract

"Acetaminophen (N-acetyl-p-aminophenol, APAP) is one of the most widely used over-the-counter antipyretic analgesic medications. It is safe at therapeutic doses, but an overdose can result in severe hepato-nephrotoxicity, a leading cause of drug-induced acute liver failure in the U.S. Although a few different mechanisms have been proposed for APAP-induced toxicity, a significant amount of evidence has pointed to the potential involvement of oxidative stress in acetaminophen toxicity. Depletion of glutathione (GSH) is one of the initiating steps in APAP-induced toxicity; therefore, one strategy for restricting organ damage is to restore GSH levels by using GSH prodrugs like N-acetylcysteine (NAC). Although NAC is the treatment of choice for APAP-induced toxicity, fairly high doses and longer treatment times are required due to its poor bioavailability. In addition, oral and IV administration of NAC in a hospital setting are laborious and costly. With limited therapeutic options, other than NAC, it is important to develop therapeutic alternatives to effectively protect against APAP-induced toxicity and to improve treatment outcomes and prevent death. Therefore, we studied the protective effects of N-acetylcysteine amide (NACA), a novel antioxidant with higher bioavailability, and compared it with NAC in APAP-induced toxicity in C57BL/6 mice. Our results showed that a lower dose of NACA is better than NAC in combating oxidative stress and protecting against APAP-induced damage. The higher efficiency of NACA, in protecting against APAP-induced toxicity, suggests that NACA can be developed into a promising therapeutic option for treatment of an APAP overdose."--Abstract, page iii.

Advisor(s)

Ercal, Nuran

Committee Member(s)

Kapila, Shubhender
Reddy, Prakash
Winiarz, Jeffrey G.
Shannon, Katie

Department(s)

Chemistry

Degree Name

Ph. D. in Chemistry

Publisher

Missouri University of Science and Technology

Publication Date

Spring 2016

Pagination

xvi, 118 pages

Note about bibliography

Includes bibliographic references (pages 105-117).

Rights

© 2016 Ahdab Naeem Khayyat, All rights reserved.

Document Type

Dissertation - Open Access

File Type

text

Language

English

Library of Congress Subject Headings

Acetaminophen -- Toxicology
Hepatotoxicology -- Testing
Antioxidants -- Therapeutic use

Thesis Number

T 10913

Electronic OCLC #

952594882

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