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Drug overdose liver failure

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https://www.readbyqxmd.com/read/29753208/mechanisms-of-acetaminophen-induced-liver-injury-and-its-implications-for-therapeutic-interventions
#1
REVIEW
Mingzhu Yan, Yazhen Huo, Shutao Yin, Hongbo Hu
Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in many developed countries. Mitochondrial oxidative stress is considered to be the predominant cellular event in APAP-induced liver injury. Accordingly, N-acetyl cysteine, a known scavenger of reactive oxygen species (ROS), is recommended as an effective clinical antidote against APAP-induced acute liver injury (AILI) when it is given at an early phase; however, the narrow therapeutic window limits its use. Hence, the development of novel therapeutic approaches that can offer broadly protective effects against AILI is clearly needed...
April 22, 2018: Redox Biology
https://www.readbyqxmd.com/read/29748533/p53-attenuates-acetaminophen-induced-hepatotoxicity-by-regulating-drug-metabolizing-enzymes-and-transporter-expression
#2
Jiahong Sun, Yajie Wen, Yanying Zhou, Yiming Jiang, Yixin Chen, Huizheng Zhang, Lihuan Guan, Xinpeng Yao, Min Huang, Huichang Bi
Acetaminophen (APAP) overdose is the most frequent cause of drug-induced acute liver failure. Inhibition of APAP metabolic activation and promotion in APAP disposition are important to protect against APAP-induced liver injury. Tumor suppressor p53 is traditionally recognized as a surveillance molecule to preserve genome integrity. Recent studies have emerged on discovering its functions in metabolic regulation. Our previous study reported that p53 promoted bile acid disposition and alleviated cholestastic syndrome...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29543434/point-of-care-determination-of-acetaminophen-levels-with-multi-hydrogen-bond-manipulated-single-molecule-recognition-emuhsir
#3
Yan Zhang, Zhongyuan Huang, Letao Wang, Chunming Wang, Changde Zhang, Thomas E Wiese, Guangdi Wang, Kevin Eugene Riley, Zhe Wang
This work aims to face the challenge of monitoring small molecule drugs accurately and rapidly for point-of-care (POC) diagnosis in current clinical settings. Overdose of acetaminophen (AP), a commonly used OTC analgesic drug, has been determined to be a major cause of acute liver failure in the US and the UK. However, there is no rapid and accurate detection method available for this drug in the emergency room. The present study examined an AP sensing strategy that relies on a previously unexplored strong interaction between AP and the arginine (Arg) molecule...
March 15, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29491713/effect-of-mrsa-on-cyp450-dynamic-changes-of-cytokines-oxidative-stress-and-drug-metabolizing-enzymes-in-mice-infected-with-mrsa
#4
Huaqiao Tang, Nana Long, Lin Lin, Yao Liu, Jianlong Li, Fenghui Sun, Lijuan Guo, Fen Zhang, Min Dai
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a very damaging and widespread pathogen, which is associated with many diseases and causes serious infections. MRSA infection can modulate the effects of drugs, which may occur through an influence on cytochrome P450 (CYP450), the drug-metabolizing enzyme in the liver. In this study, we evaluated the underlying mechanism of drug failure or poisoning in MRSA infection. Materials and methods: Mice were infected with three different doses of MRSA and the changes in CYP450 expression, cytokines, and oxidative stress markers were evaluated...
2018: Infection and Drug Resistance
https://www.readbyqxmd.com/read/29417856/gastrointestinal-safety-and-tolerability-of-oral-non-aspirin-over-the-counter-analgesics
#5
REVIEW
Nicholas Moore, James M Scheiman
Over-the-counter (OTC) analgesics are routinely used worldwide for self-management of various painful conditions. Despite this, there has been little in-depth review of the safety of non-aspirin analgesics at OTC doses. This paper reviews the available literature on the gastrointestinal (GI) and hepatic safety of non-aspirin OTC analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs; ibuprofen, ketoprofen, diclofenac, and naproxen) and acetaminophen; safety in overdose is also reviewed. Each non-aspirin OTC analgesic has a distinct adverse event (AE) profile, with GI AE rates for OTC dosing in one study ranging from 37% for diclofenac to 7...
March 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29364842/natural-dietary-pigments-potential-mediators-against-hepatic-damage-induced-by-over-the-counter-non-steroidal-anti-inflammatory-and-analgesic-drugs
#6
REVIEW
Herson Antonio González-Ponce, Ana Rosa Rincón-Sánchez, Fernando Jaramillo-Juárez, Han Moshage
Over-the-counter (OTC) analgesics are among the most widely prescribed and purchased drugs around the world. Most analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, are metabolized in the liver. The hepatocytes are responsible for drug metabolism and detoxification. Cytochrome P450 enzymes are phase I enzymes expressed mainly in hepatocytes and they account for ≈75% of the metabolism of clinically used drugs and other xenobiotics. These metabolic reactions eliminate potentially toxic compounds but, paradoxically, also result in the generation of toxic or carcinogenic metabolites...
January 24, 2018: Nutrients
https://www.readbyqxmd.com/read/29331651/activation-of-p62-keap1-nrf2-antioxidant-pathway-in-the-early-stage-of-acetaminophen-induced-acute-liver-injury-in-mice
#7
Zhenyu Shen, Yu Wang, Zhenhui Su, Ruirui Kou, Keqin Xie, Fuyong Song
Acetaminophen (APAP) overdose can cause severe liver failure even death. Nearly half of drug-induced liver injury is attributed to APAP in the US and many European countries. Oxidative stress has been validated as a critical event involved in APAP-induced liver failure. p62/SQSTM1, a selective autophagy adaptor protein, is reported to regulate Nrf2-ARE antioxidant pathway in response to oxidative stress. However, the exact role of p62-keap1-Nrf2 antioxidant pathway in APAP-induced hepatotoxicity remains unknown...
February 25, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29222960/drug-induced-acute-liver-failure-in-children-and-adults-results-of-a-single-centre-study-of-128-patients
#8
Harshad Devarbhavi, Mallikarjun Patil, Vishnu V Reddy, Rajvir Singh, Tarun Joseph, Deepak Ganga
BACKGROUND & AIMS: Drugs producing acute liver failure (ALF) are uncommon and vary geographically. Here we review the implicated drugs, clinical features, laboratory characteristics and outcome of patients with drug-induced ALF (DIALF). We analysed the predictors of mortality and their relationship with MELD, King's College criteria (KCC) and ALFSG prognostic index. METHODS: We identified DIALF patients from our drug-induced liver injury (DILI) registry (1997-2017)...
December 9, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29196879/the-feasibility-of-physiologically-based-pharmacokinetic-modeling-in-forensic-medicine-illustrated-by-the-example-of-morphine
#9
Nadine Schaefer, Daniel Moj, Thorsten Lehr, Peter H Schmidt, Frank Ramsthaler
In forensic medicine, expert opinion is often required concerning dose and time of intake of a substance, especially in the context of fatal intoxications. In the present case, a 98-year-old man died 4 days after admission to a hospital due to a femur neck fracture following a domestic fall in his retirement home. As he had obtained high morphine doses in the context of palliative therapy and a confusion of his supplemental magnesium tablets with a diuretic by the care retirement home was suspected by the relatives, a comprehensive postmortem examination was performed...
March 2018: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/29174983/comparison-of-hepatic-transcriptome-profiling-between-acute-liver-injury-and-acute-liver-failure-induced-by-acetaminophen-in-mice
#10
COMPARATIVE STUDY
Chunmin Li, Yanan Ming, Wenting Hong, Yingyue Tang, Xiaohong Lei, Xiaobo Li, Yimin Mao
Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in many countries. In the present study, we developed stable mouse models of acute drug-induced hepatic injury (DILI) and acute drug-induced hepatic failure (DILF) by sub-lethal and lethal APAP injection respectively. The differences in hepatic transcriptome profiling between these two models were compared by RNA sequencing, which were validated by qPCR, western-blot and ELISA. In results, serum IL-6, TNF-a and IL-10 levels are higher in DILF than in DILI...
February 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29136249/natural-polyphenol-chlorogenic-acid-protects-against-acetaminophen-induced-hepatotoxicity-by-activating-erk-nrf2-antioxidative-pathway
#11
Mengjuan Wei, Zhiyong Zheng, Liang Shi, Yao Jin, Lili Ji
Hepatotoxicity due to acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in clinic. Chlorogenic acid (CGA), a dietary polyphenol, was reported to prevent APAP-induced liver injury in our previous studies. This study aims to investigate the protection provided by CGA against APAP-induced hepatotoxicity via focusing on nuclear factor erythroid 2-related factor 2 (Nrf2) and extracellular regulated protein kinases (ERK)1/2. CGA prevented APAP-induced oxidative liver injury and enhanced Nrf2 activation in mice and in hepatocytes in vitro...
March 1, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29067470/multiple-micrornas-function-as-self-protective-modules-in-acetaminophen-induced-hepatotoxicity-in-humans
#12
Dianke Yu, Leihong Wu, Pritmohinder Gill, William H Tolleson, Si Chen, Jinchun Sun, Bridgett Knox, Yaqiong Jin, Wenming Xiao, Huixiao Hong, Yong Wang, Zhen Ren, Lei Guo, Nan Mei, Yongli Guo, Xi Yang, Leming Shi, Yinting Chen, Linjuan Zeng, Kostiantyn Dreval, Volodymyr Tryndyak, Igor Pogribny, Hong Fang, Tieliu Shi, Sandra McCullough, Sudeepa Bhattacharyya, Laura Schnackenberg, William Mattes, Richard D Beger, Laura James, Weida Tong, Baitang Ning
Acetaminophen (APAP) overdose is the leading cause of acute liver failure. Yet the mechanisms underlying adaptive tolerance toward APAP-induced liver injury are not fully understood. To better understand molecular mechanisms contributing to adaptive tolerance to APAP is an underpinning foundation for APAP-related precision medicine. In the current study, the mRNA and microRNA (miRNA) expression profiles derived from next generation sequencing data for APAP-treated (5 and 10 mM) HepaRG cells and controls were analyzed systematically...
February 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/28984147/celastrol-ameliorates-acetaminophen-induced-oxidative-stress-and-cytotoxicity-in-hepg2-cells
#13
A T Jannuzzi, M Kara, B Alpertunga
Acetaminophen (APAP) is the most commonly used analgesic and antipyretic drug in the world. However, hepatotoxicity caused by APAP overdose is the most frequent cause of acute liver failure worldwide and oxidative stress involved in the pathogenesis of APAP hepatotoxicity. Celastrol is a natural triterpenoid derived from Tripterygium wilfordii Hook F. that exhibits antioxidant, anti-inflammatory, and antitumor activities. In this study, we aimed to investigate the potential ameliorative effects of celastrol against APAP-induced cytotoxicity and oxidative stress...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28878168/metabolomics-analysis-of-urine-samples-from-children-after-acetaminophen-overdose
#14
Laura K Schnackenberg, Jinchun Sun, Sudeepa Bhattacharyya, Pritmohinder Gill, Laura P James, Richard D Beger
Acetaminophen (APAP), a commonly used over-the-counter analgesic, accounts for approximately fifty percent of the cases of acute liver failure (ALF) in the United States due to overdose, with over half of those unintentional. Current clinical approaches for assessing APAP overdose rely on identifying the precise time of overdose and quantitating acetaminophen alanine aminotransferase (ALT) levels in peripheral blood. Novel specific and sensitive biomarkers may provide additional information regarding patient status post overdose...
September 6, 2017: Metabolites
https://www.readbyqxmd.com/read/28770975/paracetamol-acetaminophen-for-chronic-non-cancer-pain-in-children-and-adolescents
#15
REVIEW
Tess E Cooper, Emma Fisher, Brian Anderson, Nick Mr Wilkinson, David G Williams, Christopher Eccleston
BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important...
August 2, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28729056/discovery-and-structure-activity-relationship-of-auriculatone-a-potent-hepatoprotective-agent-against-acetaminophen-induced-liver-injury
#16
Meng Zhou, Min Wang, Rui-Feng Zhong, Xiang-Ming Liao, Lian-Li Deng, Guo-Bo Xu, Xun He, Jing Li, Yong-Jun Li, Ting Liu, Yong-Lin Wang, Shang-Gao Liao
Acetaminophen (APAP, paracetamol) overdose has been the most frequent cause of drug-induced liver failure. APAP-induced liver toxicity can be fatal in many cases even with treatment of the clinically used N-acetylcysteine (NAC), and the need for novel therapeutic agents is apparent. Through evaluating the hepatoprotective effects of the co-occurring substances present in oleanolic acid tablets which have been used in China for decades as an adjuvant therapy for acute and chronic hepatitis, auriculatone was found to protect HL-7702 cells from APAP-induced liver injury comparable to NAC at the concentration of 10μM...
August 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28573237/protective-effect-of-moringa-peregrina-leaves-extract-on-acetaminophen-induced-liver-toxicity-in-albino-rats
#17
Samy Abdelfatah Abdel Azim, Mohamed Taha Abdelrahem, Mostafa Mohamed Said, Alshaimaa Khattab
BACKGROUND: Acetaminophen is a common antipyretic drug but at overdose can cause severe hepatotoxicity that may further develop into liver failure and hepatic centrilobular necrosis in experimental animals and humans. This study was undertaken to assess the ameliorative role of Moringa peregrina leaves extract against acetaminophen toxicity in rats. MATERIALS AND METHODS: Induction of hepatotoxicity was done by chronic oral administration of acetaminophen (750 mg/kg bwt) for 4 weeks...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28555165/tissue-hypoperfusion-hypercoagulopathy-and-kidney-and-liver-dysfunction-after-ingestion-of-a-naphazoline-containing-antiseptic
#18
Yuko Ono, Nozomi Ono, Kazuaki Shinohara
Naphazoline is a peripheral α2-adrenergic receptor agonist commonly used as a topical decongestant. In Japan, over-the-counter antiseptics often contain naphazoline to effect local hemostasis. We present the first case involving the development of hypercoagulopathy, with kidney and liver dysfunction, following a naphazoline overdose. A 22-year-old Japanese woman with a history of depression ingested 160 mL of a commercially available antiseptic containing 0.1% naphazoline. Three days later, she was brought to the emergency department because of general fatigue, nausea, and vomiting...
2017: Case Reports in Emergency Medicine
https://www.readbyqxmd.com/read/28462386/association-of-variants-of-arginine-vasopressin-and-arginine-vasopressin-receptor-1a-with-severe-acetaminophen-liver-injury
#19
Matthew Randesi, Orna Levran, Joel Correa da Rosa, Julia Hankins, Jody Rule, Mary Jeanne Kreek, William M Lee
BACKGROUND & AIMS: Acetaminophen-related acute liver injury and liver failure (ALF) result from ingestion of supratherapeutic quantities of this analgesic, frequently in association with other forms of substance abuse including alcohol, opioids, and cocaine. Thus, overdosing represents a unique high-risk behavior associated with other forms of drug use disorder. METHODS: We examined a series of 21 single nucleotide polymorphisms (SNPs) in 9 genes related to impulsivity and/or stress responsivity that may modify response to stress...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28459937/cxcl16-deficiency-attenuates-acetaminophen-induced-hepatotoxicity-through-decreasing-hepatic-oxidative-stress-and-inflammation-in-mice
#20
Hong Wang, Yihui Shao, Saisai Zhang, Anqi Xie, Yanna Ye, Lihua Shi, Leigang Jin, Xuebo Pan, Zhuofeng Lin, Xiaokun Li, Shulin Yang
Chemokine C-X-C ligand 16 (CXCL16), a single-pass Type I membrane protein belonging to the CXC chemokine family, is related to the inflammatory response in liver injury. In present study, we investigated the pathophysiological role of CXCL16, a unique membrane-bound chemokine, in acetaminophen (APAP)-induced hepatotoxicity in mice. Mice were injected with APAP, and blood and tissue samples were harvested at different time points. The serum high-mobility group box 1 and CXCL16 levels were quantified by sandwich immunoassays...
June 1, 2017: Acta Biochimica et Biophysica Sinica
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