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Acetaminophen overdose

Pu Reum Seok, Jung Hoan Kim, Hye Ri Kwon, Jin Sun Heo, Jong Ryeol Choi, Jae-Ho Shin
An overdose of acetaminophen (AAP) causes hepatic and renal toxicity. This study examined the protective effects of Gastrodia elata Blume (GEB) on hepatic and renal injury induced by AAP. Rats were orally administered distilled water or GEB for 14 days and injected with AAP 1 h after the oral last administration; control rats were administered water without AAP injection. All rats were sacrificed 24 h after AAP injection. The GEB pretreatment group showed decreased necrosis and the expression of pro-inflammatory cytokines in the liver and kidney...
October 2018: Food Science and Biotechnology
Y Victoria Zhang, Shu-Ling Fan, Mark D Kellogg
BACKGROUND: We evaluated the effect of hemolysis, icterus and lipemia on 3 acetaminophen assays: namely the Syva® EMIT®, the Microgenics DRI® assay, and the Roche assay on a Roche Cobas® c501 or an Integra 800 analyzer. METHODS: Discarded acetaminophen - free serum samples (blank pool) and patient serum with acetaminophen overdose were used to prepare samples. Three levels of acetaminophen (5, 10, and 30 μg/ml) were evaluated for interference: hemolysis (H index range: 0-1000), icterus (I index range: 0-40), and lipemia (L index range: 0-1000)...
October 11, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Hajar F Karaali, Ragaee R Fahmi, Jamilah M Borjac
Background Acetaminophen (APAP) is one of the most widely used drugs to treat pain. Its overdose is lethal causing liver and kidney failure. Nephrotoxicity and hepatotoxicity are mostly due to the overproduction of reactive oxygen species. Ocimum basilicum, known as basil, is a commonly used medicinal plant due to its versatile role as antibacterial, antifungal, and anti-oxidative. We aim in this study to investigate the preventive and protective effect of basil leaves aqueous extract against APAP-induced hepatorenal toxicity in BALB/c mice...
October 12, 2018: Journal of Complementary & Integrative Medicine
Eric P Brass, Randy I Burnham, Kate M Reynolds
BACKGROUND: Overdoses due to therapeutic misuse result when the maximum dose of a drug is exceeded while using it for its intended purpose, due to either intentionally exceeding the label dose, misunderstanding the label or use of more than one product with the same ingredient. Nonprescription acetaminophen-containing combination products have been hypothesized to be a risk for therapeutic misuse. This study assessed the contribution of nonprescription acetaminophen-containing products to Poison Center exposures and the time trend in these exposures since public attention was brought to their potential risks...
October 11, 2018: Clinical Toxicology
Feng-Chieh Li, Sheng-Lin Lee, Hung-Ming Lin, Chih-Ju Lin, Sheng-Shun Wang, Yu-Yuan Lee, Su-Yen Lo, Tzu-Lin Sun, Wei-Liang Chen, Wen Lo, Nicholas Horton, Chris Xu, Shu-Jen Chiang, Yang-Fang Chen, Hsuan-Shu Lee, Chen-Yuan Dong
Acetaminophen (APAP) overdose is one of the world's leading causes of drug-induced hepatotoxicity. Although traditional methods such as histological imaging and biochemical assays have been successfully applied to evaluate the extent of APAP-induced liver damage, detailed effect of how APAP overdose affect the recovery of hepatobiliary metabolism remains not completely understood. In this work, we used intravital multiphoton microscopy to image and quantify hepatobiliary metabolism of the probe 6-carboxyfluorescein diacetate (6-CFDA) in APAP-overdose mice...
October 9, 2018: Journal of Biophotonics
Nan Li, Ming Kong, Sheng Zeng, Zheng Xu, Min Li, Wenxuan Hong, Xuehui Chu, Xitai Sun, Min Zhu, Yong Xu
Acetaminophen (APAP) overdose represents the most frequent cause of acute liver failure. The underlying epigenetic mechanism is not fully understood. In the present study we investigated the mechanism whereby the chromatin remodeling protein brahma related gene 1 (Brg1) regulates APAP induced liver injury in mice. We report that hepatocyte-specific deletion of Brg1 attenuated APAP induced liver injury in mice as evidenced by reduced plasma ALT and AST levels, decreased liver necrosis, amelioration of GSH depletion, and prolonged survival...
October 2018: Biochimica et biophysica acta. Molecular basis of disease
Brian C Geohagen, Boris Korsharskyy, Amaresh Vydyanatha, Lars Nordstroem, Richard M LoPachin
Phloretin (Phl) is a dihydrochalcone flavonoid with significant cytoprotective properties; e.g., free radical trapping, electrophile scavenging. Based on this, it has been suggested that Phl might be useful in the treatment of pathogenic processes and prevention of drug toxicities. Therefore, we determined the ability of Phl to provide route- and dose-dependent hepatoprotection in a mouse model of acetaminophen (APAP) overdose. Intraperitoneal (i.p.) administration of Phl produced a bimodal effect; i.e., the highest dose (2...
October 1, 2018: Chemico-biological Interactions
Cory Anderson, Timothy Lynch, Ronish Gupta, Rodrick K Lim
BACKGROUND: Pediatric exposure to prazosin is unusual because it is most commonly indicated for the treatment of hypertension. Prazosin's increase in popularity as a treatment for posttraumatic stress disorder makes it important for emergency physicians to be aware of how to manage potential toxic ingestion because of prazosin overdose. CASE REPORT: A 16-year-old, 76-kg female presented after ingesting 110 mg of prazosin, 209.3 g of acetaminophen, and 55 g of naproxen...
October 1, 2018: Journal of Emergency Medicine
Johnny W Huang, Owen J Clarkin, Christopher McCudden, Ayub Akbari, Benjamin J W Chow, Wael Shabana, Salmaan Kanji, Alexandra Davis, Swapnil Hiremath
Background: N-acetylcysteine (NAC) is an antioxidant which can regenerate glutathione and is primarily used for acetaminophen overdose. It is also a potential therapy to prevent iatrogenic acute kidney injury or slow the progression of chronic kidney disease. It has been considered in this context by many studies with mixed results. Notably, a biological-mechanism rationale for a protective effect of NAC has never been adequately reported. Among conflicting reports, there appears to be evidence that NAC may artificially lower measured serum creatinine without improving kidney function, potentially by assay interference...
2018: Canadian Journal of Kidney Health and Disease
Min Sang Lee, Nak Won Kim, Jung Eun Lee, Myung Goo Kim, Yue Yin, Sun Young Kim, Bo Sung Ko, Aeseon Kim, Jong Han Lee, Su Yeon Lim, Dong Woo Lim, Sun Hwa Kim, Ji Won Park, Yong Taik Lim, Ji Hoon Jeong
Direct delivery of proteins into cells has been considered an effective approach for treating the protein-related diseases. However, clinical use of proteins has still been limited due to their instability in the blood and poor membrane permeability. To achieve an efficient cellular delivery of the protein to target cells via a systemic administration, a multifunctional carrier system having desirable stability both in the blood stream and the cells, specific cell-targeting property and endosomal escape functions may be required...
September 19, 2018: Acta Biomaterialia
Alexandre Mikhail, Omaid Tanoli, Gilles Légaré, Pierre-André Dubé, Youssef Habel, Alain Lesage, Nancy C P Low, Suzanne Lamarre, Santokh Singh, Elham Rahme
BACKGROUND: Over-the-counter (OTC) analgesics are frequently used in suicide attempts. Accessibility, toxicity, and unsupervised acquisition of large amounts may be facilitators. AIMS: To identify patient characteristics associated with OTC drug use as a suicide attempt method among adults. METHOD: A cross-sectional study was conducted using chart review of all individuals who presented to the emergency department (ED) of two adult general hospitals following a suicide attempt during 2009-2010 in Montreal, Canada...
September 14, 2018: Crisis
Ya-Hong He, Lei Lu, Yu-Fang Wang, Jin-Song Huang, Wei-Qin Zhu, Yan Guo, Chun-Xia Li, Hua-Ming Li
Acute pancreatitis is rarely associated with drugs. Acetaminophen overdose is a well-known cause of hepatic toxicity, but drug-induced pancreatitis is rarely reported, especially after mild overdose. A 32-year-old woman presented with nausea and vomiting for 12 h, but no abdominal pain following an overdose of eight Tylenol tablets containing acetaminophen (325 mg acetaminophen per tablet). Laboratory results on admission showed abnormal amylase and lipase levels but completely normal liver function. Magnetic resonance cholangiopancreatography revealed mild swelling of the pancreas without fluid collection around the pancreas...
September 6, 2018: World Journal of Clinical Cases
Jun Chul Park, Deok-Seo Yoon, Eunjin Byeon, Jung Soo Seo, Un-Ki Hwang, Jeonghoon Han, Jae-Seong Lee
To investigate the adverse effect of two widely used pharmaceuticals, paracetamol (acetaminophen [APAP]) and oxytetracycline (OTC) on the marine rotifer Brachionus rotundiformis (B. rotundiformis), the animals were exposed to various environmentally-relevant concentrations. Up to date, acetaminophen and oxytetracycline have been considered as toxic, if used above threshold concentration, i.e. overdosed. However, this study demonstrated these two pharmaceuticals even at low concentration (i.e., μg/L scale) elicited oxidative stress through the generation of reactive oxygen species (ROS) along with the increased glutathione S-transferase activity, despite no-observed effect in in-vivo population growth...
November 2018: Aquatic Toxicology
Hanvit Cha, Seoyoon Lee, Jin Hyup Lee, Jeen-Woo Park
Acetaminophen (N-acetyl-p-aminophenol, AAP) is an effective analgesic and antipyretic drug with minimal toxicity when used at therapeutic doses. However, AAP overdose is the most common cause of drug-induced acute liver failure and one of the main causes of morbidity and mortality. p-Coumaric acid (PCA) is the most abundant isomer of hydroxycinnamic acid in nature, and it can be widely found in fruits, vegetables, and plants products. PCA has strong antioxidant activity and exhibits protective effects in numerous disease models associated with reactive oxygen species (ROS) generation...
August 24, 2018: Food and Chemical Toxicology
Ahmaya A Mustafa, Robin Rajan, Jennifer D Suarez, Saeed K Alzghari
There is an undeniable opioid crisis in the United States that has caused significant negative consequences including many lives lost due to opioid overdoses. Currently, researchers are searching for alternatives for pain management as well as developing abuse-deterrent agents. In February 2018, the Food and Drug Administration (FDA) approved benzhydrocodone and acetaminophen (Apadaz™) for the short-term (no more than 14 days) management of acute pain severe enough to require an opioid analgesic and where alternative treatments are inadequate...
June 20, 2018: Curēus
Ting Hu, Hang Sun, Wan-Yan Deng, Wen-Qi Huang, Qi Liu
Most cases of acute liver failure are caused by acetaminophen (APAP) overdose. Oxidative stress is a key factor in APAP toxicity. While augmenter of liver regeneration (ALR) has both anti-oxidative and anti-apoptotic effects, its therapeutic potential in APAP hepatotoxicity remains unknown. The current study assessed the protective effects and associated mechanisms of ALR against APAP-induced acute liver injury in female BALB/c mice. We found that serum ALT and AST levels, intrahepatic hemorrhage and necrosis were increased at 3, 6, 12, 24, 48 and 72 h after 600 mg/kg APAP intraperitoneal injection...
August 22, 2018: Shock
Anselm Wong, Richard McNulty, David McD Taylor, Marco L A Sivilotti, Shaun Greene, Naren Gunja, Zeff Koutsogiannis, Andis Graudins
Historically, acetylcysteine has been delivered at a fixed dose and duration of 300 mg/kg over 20 hours to nearly every patient deemed to be at any risk for hepatotoxicity following acetaminophen overdose. We investigated a 12-hour treatment regimen for selected low-risk patients. This was a multicenter, open-label, cluster-controlled trial at six metropolitan emergency departments. We enrolled subjects following single or staggered acetaminophen overdose with normal serum alanine transaminase (ALT) and creatinine on presentation and at 12 hours, and acetaminophen <20mg/L at 12 hours...
August 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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 Qing 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...
October 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
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