Keywords and Phrases
Acetaminophen; Hepatotoxicity; N-acetylcysteine; N-acetylcysteine amide; Nephrotoxicity; Oxidative stress
"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.
Winiarz, Jeffrey G.
Ph. D. in Chemistry
Missouri University of Science and Technology
xvi, 118 pages
© 2016 Ahdab Naeem Khayyat, All rights reserved.
Dissertation - Open Access
Acetaminophen -- Toxicology
Hepatotoxicology -- Testing
Antioxidants -- Therapeutic use
Electronic OCLC #
Khayyat, Ahdab Naeem, "Contribution of new thiol antioxidant in the treatment of acetaminophen toxicity" (2016). Doctoral Dissertations. 2477.