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Acetaminophen overdose

Lei Li, Wenxiang Huang, Shoukai Wang, Kecheng Sun, Wenxue Zhang, Yanmei Ding, Le Zhang, Bayaer Tumen, Lili Ji, Chang Liu
Acetaminophen (APAP) is a well-known antipyretic and analgesic drug. However, the accidental or intentional APAP overdose will induce liver injury and even acute liver failure. Astragaloside IV (AS-IV), a bioactive compound isolated from Astragali Radix, has been reported to have protective effects on the digestive and immune systems because of its anti-oxidant and anti-inflammatory properties. This study aims to observe whether AS-IV pretreatment provides protection against APAP-induced liver failure. The results of serum alanine/aspartate aminotransferases (ALT/AST) analysis, hepatic glutathione (GSH), and malondialdehyde (MDA) amounts, and liver superoxide dismutase (SOD) activity showed that AS-IV protected against APAP-induced hepatotoxicity...
August 14, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Daniel P Heruth, Katherine Shortt, Nini Zhang, Ding-You Li, Li Q Zhang, Shui Q Ye
Acetaminophen is commonly used to reduce pain and fever. Unfortunately, overdose of acetaminophen is a leading cause of acute liver injury and failure in many developed countries. The majority of acetaminophen is safely metabolized in the liver and excreted in the urine; however a small percentage is converted to the highly reactive N-acetyl-p-benzoquinone imine (NAPQI). At therapeutic doses, NAPQI is inactivated by glutathione S-transferases, but at toxic levels, excess NAPQI forms reactive protein adducts that lead to hepatotoxicity...
August 3, 2018: Journal of Pharmacology and Experimental Therapeutics
Alan Moreira de Araujo, Maísa Mota Antunes, Matheus Silvério Mattos, Ariane Barros Diniz, Débora Moreira Alvarenga, Brenda Naemi Nakagaki, Érika de Carvalho, Viviane Aparecida Souza Lacerda, Raquel Carvalho-Gontijo, Jorge Goulart, Kassiana Mafra, Maria Alice Freitas-Lopes, Hortência Maciel de Castro Oliveira, Camila Miranda Dutra, Bruna Araújo David, Aristóbolo Mendes Silva, Valerie Quesniaux, Bernhard Ryffel, Sergio Costa Oliveira, Glen N Barber, Daniel Santos Mansur, Thiago Mattar Cunha, Rafael Machado Rezende, André Gustavo Oliveira, Gustavo Batista Menezes
Hepatocytes may rupture after a drug overdose, and their intracellular contents act as damage-associated molecular patterns (DAMPs) that lead to additional leukocyte infiltration, amplifying the original injury. Necrosis-derived DNA can be recognized as a DAMP, activating liver non-parenchymal cells (NPCs). We hypothesized that NPCs react to DNA by releasing interferon (IFN)-1, which amplifies acetaminophen (APAP)-triggered liver necrosis. We orally overdosed different knockout mouse strains to investigate the pathways involved in DNA-mediated amplification of APAP-induced necrosis...
July 27, 2018: Cells
Cheng Wang, Wenjing Xu, Yanqing Zhang, Dan Huang, Kai Huang
Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure and remains a critical problem in medicine. PARP1-dependent poly(ADPribosyl)ation is a key mediator of cellular stress responses and functions in multiple physiological and pathological processes. However, whether it is involved in the process of APAP metabolism remains elusive. In this study, we find that PARP1 is activated in mouse livers after APAP overdose. Pharmacological or genetic manipulations of PARP1 are sufficient to suppress the APAP-induced hepatic toxicity and injury, as well as reduced APAP metabolism...
July 26, 2018: Cell Death & Disease
Allison M Chung
OBJECTIVES: Alternating antipyretics is a common practice despite a lack of quality evidence to support it. Limited efficacy has been demonstrated, but the practice is fraught with potential safety concerns. Many pediatric organizations question the safety of this practice and do not advocate its use. Nonetheless, many physicians and pharmacists routinely recommend alternating acetaminophen (ACET) and ibuprofen (IBU) in children who are febrile. This study assesses the recommendation practices of community pharmacists regarding alternating ACET and IBU in febrile children...
July 21, 2018: Journal of the American Pharmacists Association: JAPhA
Jing Leng, Zi Wang, Cheng-Lin Fu, Jing Zhang, Shen Ren, Jun-Nan Hu, Shuang Jiang, Ying-Ping Wang, Chen Chen, Wei Li
Acute liver injury (ALI) induced by acetaminophen (APAP) overdose is the most common cause of drug-induced liver injury. Saponins from Platycodon grandiflorum (PGSs) ameliorate alcohol-induced hepatotoxicity and enhance human lung carcinoma cell death via AMPK signaling pathway. However, whether PGS could protect from APAP-induced ALI through AMPK activation and its downstream signals is still poorly elucidated. This work investigated the protective effect and the underlying mechanisms of PGS against APAP-induced liver toxicity in mouse...
July 24, 2018: Phytotherapy Research: PTR
Yakup Yesil, Abdurrahman Avar Ozdemir
Objective: To evaluate the demographic and clinical features associated with acetaminophen overdose and to identify the clinical use of IV (intravenous) N- Acetylcysteine (NAC) treatment in children. Methods: This prospective study was conducted in Kanuni Sultan Suleyman Training and Research Hospital between August 2016 and August 2017. A total of 59 patients with overdose acetaminophen ingestion were included in this study. The toxic dose for acute acetaminophen intake was defined as greater than 150 mg/kg...
May 2018: Pakistan Journal of Medical Sciences Quarterly
Chenqing Ning, Xiaoguang Gao, Changyuan Wang, Yulong Kong, Zhihao Liu, Huijun Sun, Pengyuan Sun, Xiaokui Huo, Xiaodong Ma, Qiang Meng, Kexin Liu
Acetaminophen (APAP) is a worldwide used drug for treating fever and pain. However, APAP overdose is the leading cause of drug-induced liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of ginsenoside Rg1 (Rg1), the main pharmacologically active compounds of Panax ginseng, against APAP-induced acute liver injury, and further to elucidate the involvement of Nrf2 signaling pathway by in vivo and in vitro experiments. Male C57BL/6 mice were treated with Rg1 for 3 days before injection of APAP...
July 17, 2018: Regulatory Toxicology and Pharmacology: RTP
Da Hyun Lee, Buhyun Lee, Jeong Su Park, Yu Seol Lee, Jin Hee Kim, Yejin Cho, Yoonjung Jo, Hyun-Seok Kim, Yong-Ho Lee, Ki Taek Nam, Soo Han Bae
Acetaminophen (APAP) overdose can cause hepatotoxicity by inducing mitochondrial damage and subsequent necrosis in hepatocytes. Sirtuin2 (Sirt2) is an NAD+-dependent deacetylase that regulates several biological processes, including hepatic gluconeogenesis, as well as inflammatory pathways. We show that APAP decreases the expression of Sirt2. Moreover, the ablation of Sirtuin2 attenuates APAP-induced liver injuries, such as oxidative stress and mitochondrial damage in hepatocytes. We found that Sirt2 deficiency alleviates the APAP -mediated endoplasmic reticulum stress and phosphorylation of the p70 ribosomal S6 kinase 1 (S6K1)...
July 19, 2018: BMB Reports
Joshua B Radke, Douglas A Algren, James A Chenoweth, Kelly P Owen, Jonathan B Ford, Timothy E Albertson, Mark E Sutter
Introduction: Rhabdomyolysis and delayed acetaminophen hepatotoxicity may be associated with elevated serum transaminase values. Establishing the cause of elevated transaminases may be especially difficult because of limited or inaccurate histories of acetaminophen ingestion. We hypothesized that the comparative ratios of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) can differentiate acetaminophen hepatotoxicity from rhabdomyolysis. Methods: A retrospective chart review of patients in four hospitals from 2006 to 2011 with a discharge diagnosis of acetaminophen toxicity or rhabdomyolysis was performed...
July 2018: Western Journal of Emergency Medicine
Jenny C Barker, Kaitlin DiBartola, Corinne Wee, Nicole Andonian, Mahmoud Abdel-Rasoul, Deborah Lowery, Jeffrey E Janis
BACKGROUND: The opioid epidemic demands changes in perioperative pain management. Of the 33,000 deaths due to opioid overdose in 2015, half received prescription opioids. Multimodal analgesia (MMA) is a practice-altering evolution that reduces reliance on opioid medications. Ambulatory breast surgery is an ideal opportunity to implement these strategies. METHODS: A retrospective review of 560 patients undergoing outpatient breast procedures was conducted. Patients received 1) no pre-operative analgesia (n=333), 2) intra-operative IV acetaminophen (n=78), 3) pre-operative oral acetaminophen and gabapentin (n=95), or 4) pre-operative oral acetaminophen, gabapentin and celecoxib (n=54)...
June 30, 2018: Plastic and Reconstructive Surgery
R Achterbergh, L A Lammers, L Kuijsten, H J Klümpen, R A A Mathôt, J A Romijn
INTRODUCTION: Fasting, as well as a high-fat diet, might increase the risk on acetaminophen-induced toxicity after an acute overdose. Therefore, it has been suggested to lower the threshold for acetylcysteine treatment to prevent liver injury in case of fasting. This study aims to investigate the effects of 36 hours of fasting and three days of a hypercaloric high-fat diet on acetaminophen measurement and exposure. METHODS: Nine healthy male subjects were enrolled in a randomized crossover intervention study...
July 5, 2018: Clinical Toxicology
Hongqiong Zhao, Zhihui Jiang, Xuemei Chang, Huiting Xue, Wumaierjiang Yahefu, Xiaoying Zhang
Acetaminophen (APAP) overdose is the principal cause of drug-induced acute liver failure. 4-hydroxyphenylacetic acid (4-HPA), a major microbiota-derived metabolite of polyphenols, is involved in the antioxidative action. This study seeks to investigate the ability of 4-HPA to protect against APAP-induced hepatotoxicity, as well as the putative mechanisms involved. Mice were treated with 4-HPA (6, 12, or 25 mg/kg) for 3 days, 1 h after the last administration of 4-HPA, a single dose of APAP was intraperitoneally infused for mice...
2018: Frontiers in Pharmacology
Luigino Calzetta, Maria Gabriella Matera, Paola Rogliani, Mario Cazzola
N-acetyl-l-cysteine (NAC), a derivative of the naturally occurring amino acid l-cysteine, is a mucolytic agent that may also act as an antioxidant by providing cysteine intracellularly for increased production of glutathione. It is also used for the treatment of acetaminophen overdose. Areas covered: The recent international recommendations for the treatment of chronic obstructive pulmonary disease (COPD) report that NAC, because of its mucolytic activity, reduces acute exacerbation of COPD (AECOPD) with a modest improvement in health status...
August 2018: Expert Review of Respiratory Medicine
Mohamed E Ebada
Essential oils of green cumin (Cuminum cyminum) and chamomile (Chamomilla recutita) have antioxidant and anti-inflammatory effects. Acetaminophen, N-acetyl-p-amino-phenol, is an over-the-counter analgesic and antipyretic. Despite being safe at therapeutic doses, acetaminophen overdose is a leading cause of acute liver failure. This study aimed to compare the possible protective effects of cumin and chamomile essential oils against acute acetaminophen hepatotoxicity in male rats. Cumin oil (400 mg/kg) and chamomile oil (250 mg/kg) were orally administered for 2 weeks prior to a single acetaminophen dose (1g/kg)...
June 25, 2018: Anais da Academia Brasileira de Ciências
Leeann Pavlek, Monica Kraft, Caitlyn Simmons, Mary Ryan, Pavel Prusakov, Amanda Campbell, Nicklaus Brandehoff, Patrick C Ng, Jason Russell, Steven L Ciciora, Omid Fathi
Here, we review the case of a 26 1/7 weeks' gestation premature female infant born to a mother who intentionally ingested a large quantity of Tylenol, aspirin, quetiapine, and prenatal vitamins. The neonate subsequently had markedly elevated levels of both Tylenol and aspirin when checked on the first day of life. While overall clinically stable, the neonate did demonstrate coagulopathy as evidenced by abnormal coagulation studies. Both poison control and a pediatric gastroenterologist/hepatologist were consulted...
June 26, 2018: American Journal of Perinatology
Yong-Hoon Kim, Jung-Ran Noh, Jung Hwan Hwang, Kyoung-Shim Kim, Dong-Hee Choi, Jae-Hoon Kim, Sung Je Moon, Ji Hyun Choi, Yann Hérault, Tae Geol Lee, Hueng-Sik Choi, Chul-Ho Lee
Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure. Prolonged c-Jun N-terminal kinase (JNK) activation plays a central role in APAP-induced liver injury; however, growth arrest and DNA damage-inducible 45 beta (GADD45β) is known to inhibit JNK phosphorylation. The orphan nuclear receptor small heterodimer partner (SHP, NR0B2) acts as a transcriptional co-repressor of various genes. The aim of the present study was to investigate the role of SHP in APAP-evoked hepatotoxicity...
August 2018: Archives of Toxicology
Zvi Ackerman, Galina Skarzinski, Gabriela Link, Maya Glazer, Orit Pappo, Maria Grozovski
BACKGROUND AND AIMS: Rats are resistant to acetaminophen (APAP) hepatotoxicity. In this study, we evaluated whether by augmentation of the hepatic oxidative stress, through the induction of hepatic iron overload (IO), it will be feasible to overcome the resistance of rats to the toxic effects of APAP. METHOD: Rats with no or increased hepatic IO. RESULTS: Providing iron by diet induced hepatocellular IO, while parenteral iron administration induced combined hepatocellular and sinusoidal cell IO...
July 2018: Toxicologic Pathology
Antonella Putignano, Francesco Figorilli, Eman Alabsawy, Banwari Agarwal, Rajiv Jalan
BACKGROUND AND AIMS: Acute liver failure patients who meet poor prognostic criteria have high early mortality without emergency liver transplantation. A recent study however, reported that patients that survive spontaneously have a poorer outcome compared with patients undergoing transplantation. In this single center study, we aimed to confirm or refute this observation. METHODS: Early survivors (patients who survived 90 days) were assessed for long term outcomes in 4 distinctive cohorts, incorporating aetiology (Acetaminophen overdose or non-Acetaminophen overdose related acute liver failure), and management strategy (conservative or liver transplantation)...
June 21, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Hartmut Jaeschke, Luqi Duan, Jephte Y Akakpo, Anwar Farhood, Anup Ramachandran
Although necrosis is recognized as the main mode of cell death induced by acetaminophen (APAP) overdose in animals and humans, more recently an increasing number of publications, especially in the herbal medicine and dietary supplement field, claim an important contribution of apoptotic cell death in the pathophysiology. However, most of these conclusions are based on parameters that are not specific for apoptosis. Therefore, the objective of this review was to re-visit the key signaling events of receptor-mediated apoptosis and APAP-induced programmed necrosis and critically analyze the parameters that are being used as evidence for apoptotic cell death...
June 18, 2018: Food and Chemical Toxicology
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