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Acetaminophen overdose

Rehab S Abdelrahman, Noha Abdel-Rahman
Drug-induced liver toxicity is the most frequent cause of acute liver failure worldwide. Hepatotoxicity caused by acetaminophen (ACT) overdose is mediated by its metabolic product promoting oxidative stress and activation of inflammatory mediators. Nuclear factor erythroid-related factor-2 (Nrf-2) induces the release of cytoprotective enzymes in response to electrophilic or oxidative stress and is considered a promising therapeutic target. Dimethyl fumarate (DMF) is a potent activator of (Nrf-2), its anti-inflammatory and antioxidant properties of DMF have been highlighted recently...
December 11, 2018: Life Sciences
Ki-Young Kang, Jun-Kyu Shin, Sun-Mee Lee
An overdose of acetaminophen (APAP) causes liver injury through formation of N-acetyl-p-benzoquinoneimine, which overproduces reactive oxygen species (ROS). Autophagy maintains cellular homeostasis and is regulated by generation of ROS. Pterostilbene (PTE) has been shown to have antioxidant and anti-inflammatory properties. In this study, we investigated the protective mechanisms of PTE against APAP-induced liver injury, focusing on autophagy. ICR mice were intraperitoneally (i.p.) treated with 400 mg/kg of APAP...
December 10, 2018: Food and Chemical Toxicology
K E Maduemem, C Adedokun, E Umana
Suicide is the third most common cause of death among adolescents globally, and poisoning is the leading method of attempted suicide. Survival after self-poisoning or drug overdose (OD) is common, providing an opportunity for secondary prevention. The aim of this study was to highlight pattern of presentations and preceding factors of OD in an adolescent population. We retrospectively evaluated the data of 85 adolescents presenting to a large regional hospital with OD over a 3-year period. The female-to-male ratio was 4...
April 19, 2018: Irish Medical Journal
Sandeep B Subramanya, Balaji Venkataraman, Mohamed Fizur Nagoor Meeran, Sameer N Goyal, Chandragouda R Patil, Shreesh Ojha
Acetaminophen (APAP), which is also known as paracetamol or N -acetyl- p -aminophenol is a safe and potent drug for fever, pain and inflammation when used at its normal therapeutic doses. It is available as over-the-counter drug and used by all the age groups. The overdose results in acute liver failure that often requires liver transplantation. Current clinical therapy for APAP-induced liver toxicity is the administration of N -acetyl-cysteine (NAC), a sulphydryl compound an approved drug which acts by replenishing cellular glutathione (GSH) stores in the liver...
November 28, 2018: International Journal of Molecular Sciences
Priyanka Rajaram, Ram Subramanian
Acute liver failure (ALF) is a condition that can rapidly progress to multiorgan failure. This article focuses on the diagnosis and management of ALF. We provide a detailed review of the common etiologies of ALF, including acetaminophen overdose, viral hepatitis, drug-induced liver injury, Wilson's disease, and autoimmune hepatitis. The article then addresses how to recognize ALF and reviews the role of common laboratory and imaging tests in establishing this diagnosis. The remainder of the article details the management of hepatic and extrahepatic organ dysfunctions in ALF...
October 2018: Seminars in Respiratory and Critical Care Medicine
Runkuan Yang, Tor Inge Tonnesseen
Drug hepatotoxicity is the leading cause of acute liver failure (ALF) in the developed countries. The early diagnosis and treatment are still problematic, and one important reason is the lack of reliable mechanistic biomarkers and therapeutic targets; therefore, searching for new biomarkers and therapeutic targets is urgent. Drug hepatotoxicity induces severe liver cells damage and death. Dead and damaged cells release endogenous damage-associated molecular patterns (DAMPs). Increased circulating levels of DAMPs (HMGB1, histones and DNA) can reflect the severity of drug hepatotoxicity...
November 24, 2018: Hepatology International
Carla Carnovale, Faizan Mazhar, Marco Pozzi, Marta Gentili, Emilio Clementi, Sonia Radice
OBJECTIVES: To characterize adverse reactions associated with medication errors (ME) reported in US Food and Drug Administration Adverse Event Reporting System (US-FAERS), and to identify the potential signals of disproportionate reporting (SDR) for different drugs. METHODS: ME associated Individual Case Study Report (ICSRs) were identified. ICSRs were categorized by patient age groups, affected stages of medication process and Anatomical Therapeutic Chemical classification system...
November 19, 2018: Expert Opinion on Drug Safety
Luqi Duan, Anup Ramachandran, Jephte Y Akakpo, James L Weemhoff, Steven C Curry, Hartmut Jaeschke
Formation of acetaminophen (APAP) protein adducts are a critical feature of APAP hepatotoxicity, and circulating protein adducts have recently been utilized in bioassays for identification of APAP overdose in humans. Despite their clinical significance, mechanisms of adduct release into the circulation are not well understood. Extracellular vesicles (EVs) are discrete membrane bound vesicles, which package cellular cargo and function in extracellular transport. Clarification of their role in transport of APAP adducts is relevant since adduct packaging within these vesicles could shield them from detection by antibody based methods, resulting in under-estimating adduct levels...
November 14, 2018: Toxicology Letters
Farah M Abdulkhaleq, Tawfiq M Alhussainy, Mujtaba M Badr, Asad A Abu Khalil, Omar Gammoh, Bayan Y Ghanim, Nidal A Qinna
Background: Several vitamins, including C, E, and B12 , have been recognized as antioxidants and have shown hepatoprotective effects against the hepatotoxicity caused by acetaminophen (APAP) overdose. The current investigation aims to study the effect of these vitamins and their combination in protecting the liver from APAP hepatotoxicity in rats. Materials and methods: An in vitro model of freshly isolated rat hepatocytes was utilized for assessing hepatocyte mitochondrial activity conducted by cell proliferation assay (MTT)...
2018: Drug Design, Development and Therapy
Dan-Dan Luo, Jin-Fen Chen, Jing-Jing Liu, Jian-Hui Xie, Zhen-Biao Zhang, Jiang-Yong Gu, Jian-Yi Zhuo, Song Huang, Zi-Ren Su, Zhang-Hua Sun
Acetaminophen (APAP) overdose-induced hepatotoxicity is tightly associated with oxidative stress. Tetrahydrocurcumin (THC) and octahydrocurcumin (OHC), the primary and final hydrogenated metabolites of curcumin (CUR), possess stronger antioxidant activity in vitro. The present study was performed to investigate the potential and mechanism of OHC and THC against APAP-induced hepatotoxicity in parallel to CUR. Our results showed that OHC and THC dose-dependently enhanced liver function (ALT and AST levels) and alleviated histopathological deterioration...
November 10, 2018: Food and Chemical Toxicology
Qin Feng, Ningwei Zhao, Wenkai Xia, ChengJie Liang, Guoxin Dai, Jian Yang, Jingxia Sun, Lanying Liu, Lan Luo, Jie Yang
Acetaminophen (APAP) overdose-induced acute liver injury (AILI) is a significant clinical problem worldwide, the hepatotoxicity mechanisms are well elucidated, but the factors involved in the necrosis and repair still remain to be investigated. APAP was injected intraperitoneally in male Institute of Cancer Research (ICR) mice. Quantitative proteome analysis of liver tissues was performed by 2-nitrobenzenesulfenyl tagging, two-dimensional-nano high-performance liquid chromatography separation, and matrix-assisted laser desorption/ionization-time of flight mass spectrometry analysis...
November 11, 2018: Journal of Cellular Physiology
Getaw Worku Hassen, Amaninder Dhaliwal, Catherine Ann Jenninigs, Hossein Kalantari
Background: Acute liver failure can result from acetaminophen overdose, viral infection, toxins, and other disease conditions. Liver transplant is available in limited fashion and the criteria are strict as to who should get an available liver. N- Acetyl Cysteine (NAC) has been used in non-acetaminophen induced liver failure with success. Here we report a case of acute liver failure from cocaethylene that was reversed with NAC along with other medical therapy. Case Presentation: A 50-year-old female patient presented to the Emergency Department (ED) with a two-day history of coffee ground vomiting and hematemesis...
2018: Case Reports in Emergency Medicine
Khalil Zarnousheh Farahani, Ali Benvidi, Masoud Rezaeinasab, Saleheh Abbasi, Mohammad Abdollahi-Alibeik, Ali Rezaeipoor-Anari, Mohammad Ali Karimi Zarchi, Seyed Shahab Addin Darbandizadeh Mohammad Abadi
N-acetylcysteine (N-AC) has widespread application such as pharmaceutical drug and nutritional supplement. Its adverse effects are rash, urticaria, and itchiness and large doses of N-AC could potentially cause damage to the heart and lungs. Therefore, in this work, a sensitive voltammetric sensor based on a carbon paste electrode modified with silica nano particles (i.e. Mobil Composition of Matter (No. 41) modified with Boron Trifluoride or BF3 @MCM-41) with a combination of 4,4'-dihydroxybiphenyl (DHB) (BF3 @MCM-41/DHB/CPE) was designed for determination of N-AC...
January 15, 2019: Talanta
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
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