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Open Access Acetaminophen Toxicity: Novel Insights Into Mechanisms and Future Perspectives

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Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the US, and decades of intense study of its pathogenesis resulted in the development of the antidote N-acetylcysteine, which facilitates scavenging of the reactive metabolite and is the only treatment in clinical use. However, the narrow therapeutic window of this intervention necessitates a better understanding of the intricacies of APAP-induced liver injury for the development of additional therapeutic approaches that can benefit late-presenting patients. More recent investigations into APAP hepatotoxicity have established the critical role of mitochondrial dysfunction in mediating liver injury as well as clarified mechanisms of APAP-induced hepatocyte cell death. Thus, it is now established that mitochondrial oxidative and nitrosative stress is a key mechanistic feature involved in downstream signaling after APAP overdose. The identification of specific mediators of necrotic cell death further establishes the regulated nature of APAP-induced hepatocyte cell death. In addition, the discovery of the role of mitochondrial dynamics and autophagy in APAP-induced liver injury provides additional insight into the elaborate cell signaling mechanisms involved in the pathogenesis of this important clinical problem. In spite of these new insights into the mechanisms of liver injury, significant controversy still exists on the role of innate immunity in APAP-induced hepatotoxicity.
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Keywords: Acetaminophen (APAP); Mitochondria; Neutrophils; Programmed necrosis; Sterile inflammation

Document Type: Research Article

Affiliations: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA

Publication date: March 21, 2018

This article was made available online on October 20, 2017 as a Fast Track article with title: "Acetaminophen Toxicity
Novel Insights into Mechanisms and Future Perspectives".

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  • Gene Expression, The Journal of Liver Research will publish articles in all aspects of hepatology. Hepatology, as a research discipline, has seen unprecedented growth especially in the cellular and molecular mechanisms of hepatic health and disease, which continues to have a major impact on understanding liver development, stem cells, carcinogenesis, tissue engineering, injury, repair, regeneration, immunology, metabolism, fibrosis, and transplantation. Continued research and improved understanding in these areas will have a meaningful impact on liver disease prevention, diagnosis, and treatment. The existing journal Gene Expression has expanded its focus to become Gene Expression, The Journal of Liver Research to meet this growing demand. In its revised and expanded scope, the journal will publish high-impact original articles, reviews, short but complete articles, and special articles (editorials, commentaries, opinions) on all aspects of hepatology, making it a unique and invaluable resource for readers interested in this field. The expanded team, led by an Editor-in-Chief who is uniquely qualified and a renowned expert, along with a dynamic and functional editorial board, is determined to make this a premier journal in the field of hepatology.
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