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Acetaminophen toxicity

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https://www.readbyqxmd.com/read/28928980/common-yet-elusive-a-case-of-severe-anion-gap-acidosis
#1
Akanksha Agrawal, Marina Kishlyansky, Sylvia Biso, Soumya Patnaik, Chitra Punjabi
Acid-base disturbances are common occurrence in hospitalized patients with life threatening complications. 5-oxoproline has been increasingly recognized as cause of high anion gap metabolic acidosis (AGMA) in association with chronic acetaminophen use. However, laboratory workup for it are not widely available. We report case of 56-year-old female with severe AGMA not attributable to ketoacidosis, lactic acidosis or toxic ingestion. History was significant for chronic acetaminophen use, and laboratory workup negative for all frequent causes of AGMA...
September 2017: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/28924552/schisandra-sphenanthera-extract-wuzhi-tablet-protects-against-chronic-binge-and-acute-alcohol-induced-liver-injury-by-regulating-the-nrf2-are-pathway-in-mice
#2
Xuezhen Zeng, Xi Li, Chenshu Xu, Fulin Jiang, Yufei Mo, Xiaomei Fan, Yaoting Li, Yiming Jiang, Dongshun Li, Min Huang, Huichang Bi
Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract from Schisandra sphenanthera that is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding...
September 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28918124/polyphenols-reported-to-shift-apap-induced-changes-in-mapk-signaling-and-toxicity-outcomes
#3
REVIEW
Ngoc Uy Nguyen, Brendan David Stamper
Due to its widespread availability, acetaminophen (APAP) is the leading cause for drug-induced liver injury in many countries including United States and United Kingdom. When used as recommended, APAP is relatively safe. However, in overdose cases, increased metabolism of APAP to N-acetyl-para-benzoquinoneimine (NAPQI), a reactive metabolite, leads to glutathione (GSH) depletion, oxidative stress, and cellular injury. Throughout this process, a variety of factors play important roles in propagating toxicity, including c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family...
September 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28894628/tigernut-cyperus-esculentus-l-milk-as-a-potent-nutri-drink-for-the-prevention-of-acetaminophen-induced-hepatotoxicity-in-a-murine-model
#4
Nnenna Ola Onuoha, Nneoma Oleh Ogbusua, Augustine N Okorie, Chukwunonso E C C Ejike
AIM/BACKGROUND: Given the prevalence of toxicants in foods, beauty products, etc., and the increasing demand for "green" products, there is a need for the development of "nutri-drinks" with hepatoprotective properties. The usefulness of tigernut milk (TNM) in preventing acetaminophen (APAP)-induced liver injury was, therefore, investigated. MATERIALS AND METHODS: A total of 25 rats were randomized into five equal groups. Four groups were treated with 0, 500, 1000, and 2000 kg/mg body weight (bw) TNM, respectively, per os for 2 weeks before they were challenged with 2500 mg/kg bw APAP...
July 2017: Journal of Intercultural Ethnopharmacology
https://www.readbyqxmd.com/read/28878168/metabolomics-analysis-of-urine-samples-from-children-after-acetaminophen-overdose
#5
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/28867745/non-toxic-level-of-acetaminophen-potentiates-carbon-tetrachloride-induced-hepatotoxicity-in-mice
#6
Shiori Fukaya, Hiroki Yoshioka, Tadahiro Okano, Akito Nagatsu, Nobuhiko Miura, Tsunemasa Nonogaki, Satomi Onosaka
A wide range of medications are routinely used to maintain and improve human health. Hence, it is essential that we understand and predict adverse effects caused by the combined use of multiple medications. In the present study, we investigated whether the combination of carbon tetrachloride (CCl4) and acetaminophen (APAP) had a detrimental effect on the liver. Mice injected with APAP (100 mg/kg) showed no significant changes in hepatic injury markers (alanine aminotransferase and aspartate aminotransferase), histopathological findings, pro-inflammatory cytokine levels, or hepatic oxidative stress...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28867424/psychosocial-and-behavioral-factors-in-acetaminophen-related-acute-liver-failure-and-liver-injury
#7
Carla Pezzia, Corron Sanders, Suzanne Welch, Angela Bowling, William M Lee
OBJECTIVES: Acetaminophen overdoses result in nearly 500 deaths annually and a much larger number of hospitalizations. Suicidal overdoses are exceeded in number in the United States by unintentional overdoses. We evaluated clinical, demographic and psychosocial factors among unintentional and intentional overdose patients whose acetaminophen (APAP) toxicity had resulted in acute liver failure. We hypothesized that APAP overdose patients would be more likely to suffer from behavioral health issues and display higher impulsivity scores than the general population...
October 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28834334/enhanced-hepatic-functions-of-genetically-modified-mouse-hepatoma-cells-by-spheroid-culture-for-drug-toxicity-screening
#8
Joyita Sarkar, Jyoti Kumari, Jane Marie Tonello, Masamichi Kamihira, Ashok Kumar
While hepatic cell lines are mainly used for in vitro drug induced toxicity studies, they exhibit limited functionalities. To overcome this, we have employed genetically engineered mouse hepatoma cells, Hepa/8F5, wherein expression of liver enriched transcription factors is induced by doxycycline leading to increased functionality. Further enhancement in functionality was achieved by spheroid culture in a previously developed 3D cell culture platform. Cells were seeded in presence of temperature-responsive poly(N-isopropylacrylamide) on poly(N-isopropylacrylamide-co-gelatin) cryogel scaffold based high throughput platform...
August 22, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28832650/fructose-diet-alleviates-acetaminophen-induced-hepatotoxicity-in-mice
#9
Sungjoon Cho, Ashutosh Tripathi, George Chlipala, Stefan Green, Hyunwoo Lee, Eugene B Chang, Hyunyoung Jeong
Acetaminophen (APAP) is a commonly used analgesic and antipyretic that can cause hepatotoxicity due to production of toxic metabolites via cytochrome P450 (Cyp) 1a2 and Cyp2e1. Previous studies have shown conflicting effects of fructose (the major component in Western diet) on the susceptibility to APAP-induced hepatotoxicity. To evaluate the role of fructose-supplemented diet in modulating the extent of APAP-induced liver injury, male C57BL/6J mice were given 30% (w/v) fructose in water (or regular water) for 8 weeks, followed by oral administration of APAP...
2017: PloS One
https://www.readbyqxmd.com/read/28828381/paracetamol-in-patent-ductus-arteriosus-treatment-efficacious-and-safe
#10
REVIEW
Flaminia Bardanzellu, Paola Neroni, Angelica Dessì, Vassilios Fanos
In preterm infants, failure or delay in spontaneous closure of Ductus Arteriosus (DA), resulting in the condition of Patent Ductus Arteriosus (PDA), represents a significant issue. A prolonged situation of PDA can be associated with several short- and long-term complications. Despite years of researches and clinical experience on PDA management, unresolved questions about the treatment and heterogeneity of clinical practices in different centers still remain, in particular regarding timing and modality of intervention...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28827191/silver-nanoparticles-protect-acetaminophen-induced-acute-hepatotoxicity-a-biochemical-and-histopathological-approach
#11
Mohd Salim Reshi, Chhavi Uthra, Deepa Yadav, Samta Sharma, Asha Singh, Anjali Sharma, Amita Jaswal, Neelu Sinha, Sadhana Shrivastava, Sangeeta Shukla
The present study was premeditated to demonstrate the hepatoprotective effect of silver nanoparticles (AgNPs). Rats were treated with three different doses of AgNPs (50, 100 and 150 μg/kg, p.o.) after Acetaminophen (APAP; 2 g/kg, p.o. once only) intoxication. Treatment with AgNPs recouped the levels of serum aspartate amino transaminase (AST), alanine amino transaminase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), bilirubin, triglyceride (TG) and cholesterol in dose dependent manner. Significant reduction in lipid peroxidation (LPO) and restoration of reduced glutathione (GSH) was found in liver in AgNPs treated animals...
August 19, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28827156/induction-of-mitochondrial-biogenesis-protects-against-acetaminophen-hepatotoxicity
#12
Kuo Du, Anup Ramachandran, Mitchell R McGill, Abdellah Mansouri, Tarik Asselah, Anwar Farhood, Benjamin L Woolbright, Wen-Xing Ding, Hartmut Jaeschke
Mitochondrial biogenesis (MB) is an adaptive response to maintain metabolic homeostasis after mitochondrial dysfunction. Induction of MB during APAP hepatotoxicity has not been studied. To investigate this, mice were treated with toxic doses of APAP and euthanized between 0 and 96 h. At early time points, APAP caused both mitochondrial dysfunction and reduction of mitochondrial mass, indicated by reduced activity of electron transport chain (ETC) complexes I and IV and depletion of mitochondrial DNA (mtDNA), respectively...
October 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28813206/levamisole-in-illicit-trafficking-cocaine-seized-a-one-year-study
#13
Simona Martello, Massimo Pieri, Cristiano Ialongo, Stefano Pignalosa, Gianluca Noce, Francesca Vernich, Carmelo Russo, Federico Mineo, Sergio Bernardini, Luigi Tonino Marsella
Cocaine use is increasing around the world and its purity is frequently altered through dilution, substitution, contamination, and adulteration. Sugars, talc, starch, and carbonates represent the principal diluents of cocaine, while phenacetin, levamisole, caffeine, and lidocaine are its major adulterants in Europe. Levamisole is used because it is an odorless powder, with physical properties similar to cocaine, and it has reasonable cost and availability, being widely used in veterinary medicine. For this study, we analyzed 88 cocaine samples...
August 16, 2017: Journal of Psychoactive Drugs
https://www.readbyqxmd.com/read/28799017/ecotoxicological-risk-assessment-and-seasonal-variation-of-some-pharmaceuticals-and-personal-care-products-in-the-sewage-treatment-plant-and-surface-water-bodies-lakes
#14
G Archana, Rita Dhodapkar, Anupama Kumar
This paper reports the seasonal variation and environmental quality control data for five fingerprint pharmaceuticals and personal care products (PPCPs) (acetaminophen ciprofloxacin, caffeine, irgasan and benzophenone) in the influent and the effluent of the sewage treatment plant (STP) and surface water bodies (six major lakes) in and around Nagpur, one of the "A class city" in the central India over a period of 1 year. The target compounds were analysed using developed offline solid-phase extraction (SPE) coupled with reversed phase high-performance liquid chromatography (RP-HPLC-PDA) method...
August 10, 2017: Environmental Monitoring and Assessment
https://www.readbyqxmd.com/read/28797958/quantification-of-paracetamol-and-5-oxoproline-in-serum-by-capillary-electrophoresis-implication-for-clinical-toxicology
#15
Tomáš Hložek, Tomáš Křížek, Petr Tůma, Miroslava Bursová, Pavel Coufal, Radomír Čabala
High anion gap metabolic acidosis frequently complicates acute paracetamol overdose and is generally attributed to lactic acidosis or compromised hepatic function. However, metabolic acidosis can also be caused by organic acid 5-oxoproline (pyroglutamic acid). Paracetamol's toxic intermediate, N-acetyl-p-benzoquinoneimine irreversibly binds to glutathione and its depletion leads to subsequent disruption of the gamma glutamyl cycle and an excessive 5-oxoproline generation. This is undoubtedly an underdiagnosed condition because measurement of serum 5-oxoproline level is not readily available...
October 25, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28795995/toxic-myocarditis-caused-by-acetaminophen-in-a-multidrug-overdose
#16
Maxime Gosselin, Yann Dazé, Pascal Mireault, Marie Crahes
We report the case of an 18-year-old woman with personality disorders who was hospitalized a few hours after suicidal ingestion of acetaminophen, quetiapine, acetylsalicylic acid, and ethanol. Twelve hours after admission, severe liver damage was evident, but the patient was stable and awaiting hepatic transplantation. Electrolytes were successfully controlled. The condition of the liver stabilized. Cardiac biomarkers then deteriorated unexpectedly. Localized ST-segment elevations were noted on electrocardiogram, but angiography ruled out myocardial infarction...
August 9, 2017: American Journal of Forensic Medicine and Pathology
https://www.readbyqxmd.com/read/28782093/metabolic-acidosis-caused-by-concomitant-use-of-paracetamol-acetaminophen-and-flucloxacillin-a-case-report-and-a-retrospective-study
#17
J K Berbee, L A Lammers, C T P Krediet, J C Fischer, E M Kemper
PURPOSE: A patient was identified with severe metabolic acidosis, a high anion gap and 5-oxoproline accumulation, probably caused by the simultaneous use of paracetamol (acetaminophen) and flucloxacillin. We wanted to investigate the necessity to control the interaction between both drugs with an automatic alert system. METHODS: To investigate the relevance of the interaction of paracetamol and flucloxacillin, a retrospective study was conducted. Data on paracetamol and flucloxacillin prescriptions and laboratory data (pH, Na(+), HCO3(-), Cl(-), albumin and 5-oxoproline levels) were combined to assess the prevalence of acidosis, calculate the anion gap and analyse 5-oxoproline levels in clinically admitted patients using both drugs simultaneously...
August 7, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28772250/formation-and-estimated-toxicity-of-trihalomethanes-haloacetonitriles-and-haloacetamides-from-the-chlor-am-ination-of-acetaminophen
#18
Shunke Ding, Wenhai Chu, Tom Bond, Qi Wang, Naiyun Gao, Bin Xu, Erdeng Du
The occurrence of pharmaceuticals and personal care products (PPCPs) in natural waters, which act as drinking water sources, raises concerns. Moreover, those compounds incompletely removed by treatment have the chance to form toxic disinfection byproducts (DBPs) during subsequent disinfection. In this study, acetaminophen (Apap), commonly used to treat pain and fever, was selected as a model PPCP. The formation of carbonaceous and nitrogenous DBPs, namely trihalomethanes, haloacetonitriles, and haloacetamides, during chlor(am)ination of Apap was investigated...
July 25, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28772086/highlights-of-drug-and-herb-induced-liver-injury-in-the-literature-from-2016-how-best-to-translate-new-information-into-clinical-practice
#19
REVIEW
Omar Shahbaz, Sandeep Mahajan, James H Lewis
Over 1500 papers on drug-induced liver injury (DILI) and herb-induced liver injury (HILI) were published in 2016, many of which have the potential to impact clinical practice. Areas covered: Clinical studies and case series that lent themselves to new concepts in diagnosing, and treating DILI were selected for inclusion. Epidemiology of DILI in large prospective registries was highlighted. Causality assessment of drug hepatotoxicity remains challenging, as seen with cases of OxyELITE Pro (OEP). In 2016 updates to the Roussel Uclaf Causality Assessment Method (RUCAM) were published to aid in the accuracy of diagnosing DILI/HILI...
September 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28766237/the-toxicology-investigators-consortium-case-registry-the-2016-experience
#20
Lynn A Farrugia, Sean H Rhyee, Diane P Calello, Sharan L Campleman, Anne M Riederer, Hannah R Malashock, Anthony Pizon, Timothy Wiegand, Paul M Wax, Jeffrey Brent
The Toxicology Investigators Consortium (ToxIC) Case Registry was established by the American College of Medical Toxicology in 2010. The Registry contains data from participating sites with the agreement that all bedside medical toxicology consultations will be entered. Currently, 83% of accredited medical toxicology fellowship programs in the USA participate. The Registry continues to grow each year, and as of 31 December 2016, a new milestone was reached, with more than 50,000 cases reported since its inception...
August 1, 2017: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
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