文章基本信息

标题：Toxicological Property of Acetaminophen: The Dark Side of a Safe Antipyretic/Analgesic Drug?
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作者：Yoichi Ishitsuka ; Yuki Kondo ; Daisuke Kadowaki 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2020
卷号：43
期号：2
页码：195-206
DOI：10.1248/bpb.b19-00722
出版社：The Pharmaceutical Society of Japan
摘要：Acetaminophen (paracetamol, N -acetyl- p -aminophenol; APAP) is the most popular analgesic/antipyretic agent in the world. APAP has been regarded as a safer drug compared with non-steroidal anti-inflammatory drugs (NSAIDs) particularly in terms of lower risks of renal dysfunction, gastrointestinal injury, and asthma/bronchospasm induction, even in high-risk patients such as the elderly, children, and pregnant women. On the other hand, the recent increasing use of APAP has raised concerns about its toxicity. In this article, we review recent pharmacological and toxicological findings about APAP from basic, clinical, and epidemiological studies, including spontaneous drug adverse events reporting system, especially focusing on drug-induced asthma and pre-and post-natal closure of ductus arteriosus. Hepatotoxicity is the greatest fault of APAP and the most frequent cause of drug-induced acute liver failure in Western countries. However, its precise mechanism remains unclear and no effective cure beyond N -acetylcysteine has been developed. Recent animal and cellular studies have demonstrated that some cellular events, such as c-jun N-terminal kinase (JNK) pathway activation, endoplasmic reticulum (ER) stress, and mitochondrial oxidative stress may play important roles in the development of hepatitis. Herein, the molecular mechanisms of APAP hepatotoxicity are summarized. We also discuss the not-so-familiar “dark side” of APAP as an otherwise safe analgesic/antipyretic drug..
关键词：acetaminophen (APAP);drug;induced asthma;ductus arteriosus;hepatotoxicity;mitochondria;endoplasmic reticulum stress