4,015 results match your criteria Toxicity Acetaminophen


Animal models of drug-induced liver injury.

Biochim Biophys Acta Mol Basis Dis 2019 May 3;1865(5):1031-1039. Epub 2018 Sep 3.

Dept. of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address:

Drug-induced liver injury (DILI) presents unique challenges for consumers, clinicians, and regulators. It is the most common cause of acute liver failure in the US. It is also one of the most common reasons for termination of new drugs during pre-clinical testing and withdrawal of new drugs post-marketing. Read More

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http://dx.doi.org/10.1016/j.bbadis.2018.08.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478394PMC

The Relationship Between Circulating Acetaminophen-Protein Adduct Concentrations and Alanine Aminotransferase Activities in Patients With and Without Acetaminophen Overdose and Toxicity.

J Med Toxicol 2019 Apr 12. Epub 2019 Apr 12.

Department of Medical Toxicology, Banner-University Medical Center Phoenix, Phoenix, AZ, USA.

Introduction: Measurement of serum acetaminophen-protein adducts (APAP-CYS) has been suggested to support or refute a diagnosis of acetaminophen (APAP)-induced hepatotoxicity when ingestion histories are unreliable or unavailable and when circulating APAP concentrations are low or undetectable. Non-APAP overdose patients commonly have used APAP products in non-toxic quantities and, thus, will have measurable APAP-CYS concentrations, even when hepatic injury results from other causes, such as ischemic hepatitis. The relationship between alanine aminotransferase (ALT) activity and APAP-CYS concentration might assist in distinguishing between toxic and non-toxic APAP doses in patients suspected of drug overdose. Read More

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http://dx.doi.org/10.1007/s13181-019-00705-2DOI Listing
April 2019
1 Read

Mechanistic identification of biofluid metabolite changes as markers of acetaminophen-induced liver toxicity in rats.

Toxicol Appl Pharmacol 2019 Apr 8;372:19-32. Epub 2019 Apr 8.

Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Fort Detrick, MD 21702, USA. Electronic address:

Acetaminophen (APAP) is the most commonly used analgesic and antipyretic drug in the world. Yet, it poses a major risk of liver injury when taken in excess of the therapeutic dose. Current clinical markers do not detect the early onset of liver injury associated with excess APAP-information that is vital to reverse injury progression through available therapeutic interventions. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0041008X193012
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http://dx.doi.org/10.1016/j.taap.2019.04.001DOI Listing
April 2019
12 Reads

An unexpected role of cholesterol sulfotransferase and its regulation in sensitizing mice to acetaminophen induced liver injury.

Mol Pharmacol 2019 Apr 3. Epub 2019 Apr 3.

University of Pittsburgh

Overdose of acetaminophen (APAP) is the leading cause of acute liver failure (ALF) in the United States. The sulfotransferase-mediated sulfation of APAP is widely believed to be a protective mechanism to attenuate the hepatotoxicity of APAP. The cholesterol sulfotransferase SULT2B1b is best known for its activity in catalyzing the sulfoconjugation of cholesterol to synthesize cholesterol sulfate. Read More

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http://dx.doi.org/10.1124/mol.118.114819DOI Listing
April 2019
4 Reads

Drug repurposing of N-acetyl cysteine as antiviral against dengue virus infection.

Antiviral Res 2019 Mar 27;166:42-55. Epub 2019 Mar 27.

Siriraj Center of Research Excellence for Molecular Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Electronic address:

Liver injury is one of the hallmark features of severe dengue virus (DENV) infection since DENV can replicate in the liver and induce hepatocytes to undergo apoptosis. N-acetyl cysteine (NAC), which is a clinically-used drug for treating acetaminophen toxicity, was found to benefit patients with DENV-induced liver injury; however, its mechanism of action remains unclear. Accordingly, our aim was to repurpose NAC in the preclinical studies to investigate its mechanism of action. Read More

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http://dx.doi.org/10.1016/j.antiviral.2019.03.011DOI Listing
March 2019
2 Reads
3.938 Impact Factor

Integrated in vitro models for hepatic safety and metabolism: evaluation of a human Liver-Chip and liver spheroid.

Arch Toxicol 2019 Mar 26. Epub 2019 Mar 26.

Drug Safety and Metabolism, AstraZeneca IMED Biotech Unit, Cambridge, CB4 0WG, UK.

Drug-induced liver injury remains a frequent reason for drug withdrawal. Accordingly, more predictive and translational models are required to assess human hepatotoxicity risk. This study presents a comprehensive evaluation of two promising models to assess mechanistic hepatotoxicity, microengineered Organ-Chips and 3D hepatic spheroids, which have enhanced liver phenotype, metabolic activity and stability in culture not attainable with conventional 2D models. Read More

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http://dx.doi.org/10.1007/s00204-019-02427-4DOI Listing
March 2019
1 Read

Chronic copper treatment prevents the liver critical balance transcription response induced by acetaminophen.

J Trace Elem Med Biol 2019 May 21;53:113-119. Epub 2019 Feb 21.

Gastroenterología y Nutrición, INTA, Universidad de Chile, El Líbano 5524, Macul, Santiago, Chile. Electronic address:

The independent toxic effects of copper and acetaminophen are among the most studied topics in liver toxicity. Here, in an animal model of Cebus capucinus chronically exposed to high dietary copper, we assessed clinical and global transcriptional adaptations of the liver induced by a single high dose of acetaminophen. The experiment conditions were chosen to resemble a close to human real-life situation of exposure to both toxic stimuli. Read More

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http://dx.doi.org/10.1016/j.jtemb.2019.02.007DOI Listing
May 2019
1 Read

Delayed Treatment with 4-Methylpyrazole Protects against Acetaminophen Hepatotoxicity in Mice by Inhibition of c-Jun N-Terminal Kinase.

Toxicol Sci 2019 Mar 23. Epub 2019 Mar 23.

Department of Emergency Medicine and Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.

Acetaminophen (APAP) overdose is the most common cause of hepatotoxicity and acute liver failure in the US and many western countries. However, the only clinically approved antidote, N-acetylcysteine, has a limited therapeutic window. 4-Methylpyrazole (4MP) is an antidote for methanol and ethylene glycol poisoning, and we have recently shown that co-treatment of 4MP with APAP effectively prevents toxicity by inhibiting Cyp2E1. Read More

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http://dx.doi.org/10.1093/toxsci/kfz077DOI Listing
March 2019
1 Read

Use of a Bile Salt Export Pump Knockdown Rat Susceptibility Model to Interrogate Mechanism of Drug Induced Liver Toxicity.

Toxicol Sci 2019 Mar 23. Epub 2019 Mar 23.

Safety Assessment and Laboratory Animal Resources MRL, Kenilworth, NJ, USA.

Inhibition of the Bile Salt Export Pump (BSEP) may be associated with clinical drug-induced liver injury, but is poorly predicted by preclinical animal models. Here we present the development of a novel rat model using siRNA knockdown (KD) of Bsep that displayed differentially enhanced hepatotoxicity to 8 Bsep inhibitors and not to 3 Bsep non-inhibitors when administered at maximally tolerated doses for 7 days. Bsep KD alone resulted in 3- and 4. Read More

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http://dx.doi.org/10.1093/toxsci/kfz079DOI Listing
March 2019
1 Read

Hematoprotective effects and antioxidant properties of β-glucan and vitamin C against acetaminophen-induced toxicity: an experimental study in rats.

Drug Chem Toxicol 2019 Mar 18:1-8. Epub 2019 Mar 18.

b Institute for Biological Research "Siniša Stanković" , University of Belgrade , Belgrade , Republic of Serbia.

Acetaminophen is widely used as an over-the-counter analgesic and antipyretic drug. The aim of the present study was to investigate the pro-oxidative effects of acetaminophen (300 mg/kg/day i.p. Read More

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http://dx.doi.org/10.1080/01480545.2019.1587451DOI Listing
March 2019
2 Reads

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives.

J Clin Transl Res 2018 May 28;4(1):75-100. Epub 2018 May 28.

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States.

Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410631PMC
May 2018
3 Reads

Ophthalmic acid as a read-out for hepatic glutathione metabolism in humans.

J Clin Transl Res 2018 Jul 25;3(Suppl 2):366-374. Epub 2018 Mar 25.

Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands.

Background And Aim: Animal studies indicated that systemic ophthalmic acid (OPH) is a biomarker for hepatic glutathione (GSH) homeostasis, an important determinant of liver function. We aimed to clarify whether OPH levels can be used as a read-out for hepatic GSH homeostasis after paracetamol (APAP) challenges during pylorus-preserving pancreaticoduodenectomy (PPPD) or partial hepatectomy (PH).

Methods: Nineteen patients undergoing PPPD (n=7, control group) or PH (n=12) were included. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412618PMC
July 2018
3 Reads

Acetaminophen Hepatotoxicity.

Semin Liver Dis 2019 Mar 8. Epub 2019 Mar 8.

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas.

Acetaminophen (APAP) is one of the most popular and safe pain medications worldwide. However, due to its wide availability, it is frequently implicated in intentional or unintentional overdoses where it can cause severe liver injury and even acute liver failure (ALF). In fact, APAP toxicity is responsible for 46% of all ALF cases in the United States. Read More

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http://dx.doi.org/10.1055/s-0039-1679919DOI Listing
March 2019
1 Read

Identification of serum microRNAs as potential toxicological biomarkers for toosendanin-induced liver injury in mice.

Phytomedicine 2019 Feb 18;58:152867. Epub 2019 Feb 18.

The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Background: Toosendan Fructus is traditionally used as an insecticide or digestive tract parasiticide for treating digestive parasites in China. It is recorded to have little toxicity in Chinese Pharmacopoeia and has been found to cause severe liver injury during clinical practice.

Purpose: This study aims to identify candidate serum microRNAs (miRNAs) as potential toxicological biomarkers for reflecting the hepatotoxicity induced by toosendanin (TSN), which is the main toxic compound isolated from Toosendan Fructus METHODS: Alanine/aspartate aminotransferase (ALT/AST) activities detection and liver histological observation were performed to evaluate the liver injury induced by TSN or other hepatotoxicants in mice. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09447113193003
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http://dx.doi.org/10.1016/j.phymed.2019.152867DOI Listing
February 2019
6 Reads
3.126 Impact Factor

Neutrophils promote the development of reparative macrophages mediated by ROS to orchestrate liver repair.

Nat Commun 2019 03 6;10(1):1076. Epub 2019 Mar 6.

State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing. Beijing Proteome Research Center, Beijing Institute of Lifeomics, 102206, Beijing, China.

Phagocytes, including neutrophils and macrophages, have been suggested to function in a cooperative way in the initial phase of inflammatory responses, but their interaction and integration in the resolution of inflammation and tissue repair remain unclear. Here we show that neutrophils have crucial functions in liver repair by promoting the phenotypic conversion of pro-inflammatory Ly6CCXCR1 monocytes/macrophages to pro-resolving Ly6CCXCR1 macrophages. Intriguingly, reactive oxygen species (ROS), expressed predominantly by neutrophils, are important mediators that trigger this phenotypic conversion to promote liver repair. Read More

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http://dx.doi.org/10.1038/s41467-019-09046-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403250PMC
March 2019
2 Reads
10.742 Impact Factor

Thymoquinone and curcumin modify iNOS, caspase-3, and thioredoxin immunohistochemical expression in acetaminophen (APAP) hepatotoxicity.

Folia Morphol (Warsz) 2019 Mar 5. Epub 2019 Mar 5.

Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Acetaminophen (APAP) hepatotoxicity is characterized by an extensive oxidative stress due to depletion of glutathione (GSH), which results in massive lipid peroxidation and subsequent liver injury. The current paradigm suggests that mitochondria are the main source of reactive oxygen species (ROS), which impair mitochondrial function and are responsible for cell signaling resulting in cell death. This study was designed to compare the potential impact of thymoquinone (THQ), and/or curcumin (CURC) on liver injury induced by APAP toxicity in rats. Read More

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http://dx.doi.org/10.5603/FM.a2019.0027DOI Listing
March 2019
3 Reads

Kernels Prevent Paracetamol-Induced Hepatotoxicity by Inducing Anti-Apoptotic Genes and Nrf2/HO-1 Pathway.

Int J Mol Sci 2019 Feb 25;20(4). Epub 2019 Feb 25.

Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.

Paracetamol is responsible for acute liver failure in humans and experimental animals when taken at high doses and transformed into a reactive metabolite by the liver cytochrome P450. On the other hand, nutmeg is rich with many phytochemical ingredients that are known for their ability to inhibit cytochrome P450. Hence, the present experiment was aimed at studying the hepatoprotective effect of (nutmeg), kernel extract (MFKE) in respect to paracetamol (acetaminophen; -acetyl-p-amino-phenol (APAP))-induced hepatotoxicity in rats, focusing on its antioxidant, anti-inflammatory, and anti-apoptotic activities. Read More

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http://dx.doi.org/10.3390/ijms20040993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412641PMC
February 2019
3 Reads
2.862 Impact Factor

Video delivery of toxicology educational content versus textbook for asynchronous learning, using acetaminophen overdose as a topic.

Clin Toxicol (Phila) 2019 Feb 26:1-5. Epub 2019 Feb 26.

c Department of Emergency Medicine , University of Colorado School of Medicine , Aurora , USA.

Objectives: Advances in technology have brought with them innovations in delivery of medical educational content; for example, audio and video podcasts, flipped classroom learning, and e-books. These new modalities may be useful for delivery of content asynchronously, as an adjunct to traditional lecture-based and bedside clinical teaching. Here, we measured the differences in knowledge acquisition between medical students using a video-based content delivery method and students using a traditional method of asynchronous content delivery (a textbook chapter). Read More

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http://dx.doi.org/10.1080/15563650.2019.1574974DOI Listing
February 2019
2 Reads

What is the most appropriate dose of N-acetylcysteine after massive acetaminophen overdose?

Clin Toxicol (Phila) 2019 Feb 19:1-6. Epub 2019 Feb 19.

a Department of Emergency Medicine , Oregon Health and Science University , Portland , OR , USA.

While the traditional intravenous N-acetylcysteine (NAC) dosing regimen works well for the vast majority of acetaminophen overdoses, there may be cases of massive overdose where additional NAC may be necessary. Recent evidence suggests that patients with acetaminophen concentrations above the "300-line" develop hepatotoxicity at a higher rate than those below the 300-line, suggesting that an increase of dose may be beneficial at this cut-off. Additional clinical data suggest a further increase in doses at the 450-line and 600-lines. Read More

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http://dx.doi.org/10.1080/15563650.2019.1579914DOI Listing
February 2019
3 Reads

Core Entrustable Professional Activities in Clinical Pharmacology for Entering Residency: Common Problem Drugs and How to Prescribe Them.

J Clin Pharmacol 2019 Feb 15. Epub 2019 Feb 15.

The American College of Clinical Pharmacology, Ashburn, VA, USA.

Although the medical profession strives for safe prescribing, most medications are unique challenges even when prescribed by an experienced provider. In this article we discuss the pitfalls associated with drug interactions between commonly used antibiotics and anticoagulants, the complexities associated with the administration of novel reversible anticoagulants, the often-overlooked severe adverse drug reactions from commonly used classes of medications such as corticosteroids, the nuances of managing an acetaminophen overdose, and uncommon yet serious adverse events associated with the use of contraceptive hormone drugs. Read More

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http://dx.doi.org/10.1002/jcph.1389DOI Listing
February 2019
2 Reads

Effects of acetaminophen in oxidative stress and neurotoxicity biomarkers of the gastropod Phorcus lineatus.

Environ Sci Pollut Res Int 2019 Apr 8;26(10):9823-9831. Epub 2019 Feb 8.

Departamento de Biologia, Universidade de Aveiro, Campus de Santiago, 3810-193, Aveiro, Portugal.

The growing use of pharmaceutical drugs has become a major environmental issue considering that these substances (or their metabolites) end up inevitably in sewage waters after excretion. In the wild, these chemicals may affect non-target organisms, and their potential toxicity is not sufficiently studied, a reality that is particularly true for marine organisms. Acetaminophen (also known as paracetamol) is known to be toxic in high dosages, namely, by triggering oxidative effects. Read More

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http://dx.doi.org/10.1007/s11356-019-04349-1DOI Listing
April 2019
2 Reads

Acetaminophen is Undetectable in Plasma From More Than Half of Patients Believed to Have Acute Liver Failure Due to Overdose.

Clin Gastroenterol Hepatol 2019 Feb 5. Epub 2019 Feb 5.

Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas.

Background & Aims: Evaluation of patients with acute liver injury (ALI) or acute liver failure (ALF) often includes measurement of plasma levels of acetaminophen, to determine exposure and/or toxicity. However, once liver injury has developed, acetaminophen might be undetectable in plasma. We investigated the association between level of acetaminophen measured and outcomes of patients designated as having ALF or ALI due to acetaminophen toxicity. Read More

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http://dx.doi.org/10.1016/j.cgh.2019.01.040DOI Listing
February 2019
3 Reads

Comparison of RNA-Seq and Microarray Gene Expression Platforms for the Toxicogenomic Evaluation of Liver From Short-Term Rat Toxicity Studies.

Front Genet 2018 22;9:636. Epub 2019 Jan 22.

Investigative Toxicology and Pathology, Global Preclinical Safety, AbbVie, North Chicago, IL, United States.

Gene expression profiling is a useful tool to predict and interrogate mechanisms of toxicity. RNA-Seq technology has emerged as an attractive alternative to traditional microarray platforms for conducting transcriptional profiling. The objective of this work was to compare both transcriptomic platforms to determine whether RNA-Seq offered significant advantages over microarrays for toxicogenomic studies. Read More

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http://dx.doi.org/10.3389/fgene.2018.00636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349826PMC
January 2019
4 Reads

Identification of Novel Regulatory Genes in APAP Induced Hepatocyte Toxicity by a Genome-Wide CRISPR-Cas9 Screen.

Sci Rep 2019 Feb 4;9(1):1396. Epub 2019 Feb 4.

Division of Experimental and Translational Genetics, University of Missouri Kansas City School of Medicine, Kansas City, USA.

Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. Read More

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http://dx.doi.org/10.1038/s41598-018-37940-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362041PMC
February 2019
2 Reads

Mannan-binding lectin attenuates acetaminophen-induced hepatotoxicity by regulating CYP2E1 expression via ROS-dependent JNK/SP1 pathway.

Eur J Immunol 2019 Apr 12;49(4):564-575. Epub 2019 Feb 12.

Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

Mannan-binding lectin (MBL) acts as a soluble pattern recognition molecule in the innate immune system, which is primarily produced by the liver. MBL deficiency occurs with high frequency in the population and is reported to be associated with susceptibility to several liver diseases. In the present study, we investigated the pathophysiological role of MBL in acetaminophen (APAP)-induced hepatotoxicity. Read More

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http://dx.doi.org/10.1002/eji.201847830DOI Listing
April 2019
4 Reads

Safety investigation of Pulsatilla chinensis saponins from chronic metabonomic study of serum biomedical changes in oral treated rat.

J Ethnopharmacol 2019 May 28;235:435-445. Epub 2019 Jan 28.

Jiangxi University of Traditional Chinese Medicine, 1688 Meiling Road, Nanchang 330004, PR China. Electronic address:

Ethnopharmacological Relevance: Pulsatilla chinensis (Bunge) Regel is a valuable traditional Chinese medicine (TCM) which is widely used for the treatment of schistosomiasis, inflammatory, bacterial infections. In recent years, P chinensis has been reported to exhibit antitumor activities. However, the mechanisms underlying its toxic effects remain largely unresolved. Read More

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http://dx.doi.org/10.1016/j.jep.2019.01.035DOI Listing
May 2019
1 Read

Can acetaminophen/dimethyl sulfoxide formulation prevent accidental and intentional acetaminophen hepatotoxicity?

Drug Dev Res 2019 Jan 30. Epub 2019 Jan 30.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.

An overdose of acetaminophen (APAP) causes liver injury in experimental animals and humans. The activation step (formation of reactive metabolite, N-acetyl-p-benzoquinone imine by cytochrome P450 system) and the consequent downstream pathway of oxidative stress, nitrosative stress, and inflammation play an important role in APAP-induced hepatotoxicity. Formulation of APAP with an inhibitor of the activation step would be ideal to prevent accidental and intentional APAP toxicity. Read More

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http://dx.doi.org/10.1002/ddr.21520DOI Listing
January 2019
3 Reads
0.734 Impact Factor

Evaluation of pharmaceutical toxic effects of non-standard endpoints on the macrophyte species Lemna minor and Lemna gibba.

Sci Total Environ 2019 Mar 2;657:926-937. Epub 2018 Dec 2.

Department of Biology, Aveiro University, Campus de Santiago, 3810-193 Aveiro, Portugal; Centre for Environmental and Marine Studies (CESAM), Campus de Santiago, Universidade de Aveiro, 3810-193 Aveiro, Portugal. Electronic address:

In the last years the environmental presence of pharmaceuticals has gained increasing attention. Research data show that these compounds can cause toxicological effects in different species of fish, mollusks and macroinvertebrates. However, the literature is scarce in terms of ecotoxicity data especially focusing on plants as test organisms. Read More

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http://dx.doi.org/10.1016/j.scitotenv.2018.12.002DOI Listing
March 2019
1 Read

Transformation of endocrine disrupting chemicals, pharmaceutical and personal care products during drinking water disinfection.

Sci Total Environ 2019 Mar 11;657:1480-1490. Epub 2018 Dec 11.

Australian Rivers Institute, School of Environment and Science, Griffith University, Southport, Qld 4222, Australia; The University of Queensland, Queensland Alliance for Environmental Health Sciences (QAEHS), Woolloongabba, Qld 4102, Australia; UFZ - Helmholtz Centre for Environmental Research, Cell Toxicology, 04318 Leipzig, Germany.

Pharmaceuticals and personal care products (PPCPs) and endocrine disrupting compounds (EDCs) are frequently detected in drinking water sources. This raises concerns about the formation of potentially more toxic transformation products (TPs) after drinking water disinfection. This study applied a combination of computational and experimental methods to investigate the biological activity of eight EDCs and PPCPs commonly detected in source waters (acetaminophen, bisphenol A, carbamazepine, estrone, 17α-ethinylestradiol, gemfibrozil, naproxen and triclosan) before and after disinfection. Read More

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http://dx.doi.org/10.1016/j.scitotenv.2018.12.106DOI Listing
March 2019
1 Read
4.099 Impact Factor

Green synthesized selenium nanoparticles using Spermacoce hispida as carrier of s-allyl glutathione: to accomplish hepatoprotective and nephroprotective activity against acetaminophen toxicity.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):56-63

a Department of Biochemistry, Molecular Therapeutics Laboratory , Periyar University , Salem , India.

s-allyl glutathione (SAG) an analogue of glutathione is explored for its antioxidative and liver protection property in recent years. Selenium nanoparticles (Sh-SeNPs) were synthesized using medicinal plant Spermacoce hispida and conjugated with SAG (SAG-Sh-SeNPs). SAG-Sh-SeNPs and Sh-SeNPs were characterized using by Fourier transform infrared spectroscopy, Transmission electron microscopy, Energy dispersive X-ray analysis, X-ray diffraction analysis and zeta potential analysis. Read More

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http://dx.doi.org/10.1080/21691401.2018.1543192DOI Listing
December 2019
2 Reads

The inhibitor of glycerol 3-phosphate acyltransferase FSG67 blunts liver regeneration after acetaminophen overdose by altering GSK3β and Wnt/β-catenin signaling.

Food Chem Toxicol 2019 Mar 14;125:279-288. Epub 2019 Jan 14.

Dept. of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Dept. of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Center for Dietary Supplement Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address:

Repair mechanisms after acetaminophen (APAP) hepatotoxicity are poorly understood. We recently discovered that phosphatidic acid (PA) increases in mice and humans after APAP overdose, and is critical for liver regeneration. Here, we hypothesized that PA inhibits glycogen synthase kinase-3β (GSK3β), a component of canonical Wnt/β-catenin signaling, after APAP overdose. Read More

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http://dx.doi.org/10.1016/j.fct.2019.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443093PMC
March 2019
5 Reads

Safety Issues of Pharmacological Acute Pain Treatment in Children.

Clin Pharmacol Ther 2019 May 1;105(5):1130-1138. Epub 2019 Mar 1.

Division of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Intensive Care, and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland.

Acute nociceptive pain management in children is a major public health concern. Effective and safe pain treatment is essential, but safety data cannot be simply extrapolated from adults to children due to pharmacokinetic and pharmacodynamic specificities. In addition, the frequent absence of child-specific data, the difficulty to assess drug tolerability, and the infants' inability to communicate properly and voluntarily report adverse drug reactions make children more vulnerable to safety issues. Read More

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http://dx.doi.org/10.1002/cpt.1358DOI Listing
May 2019
13 Reads

Effects of hydrogen sulfide on acetaminophen-induced acute renal toxicity in rats.

Int Urol Nephrol 2019 Apr 2;51(4):745-754. Epub 2019 Jan 2.

Department of Biology, Faculty of Science and Literature, Kutahya Dumlupinar University, Kutahya, Turkey.

Introduction And Aim: Hydrogen sulfide (HS) is an endogenously produced gas-structure mediator. It is proposed to have antioxidant, anti-inflammatory and antiapoptotic effects. Acetaminophen (N-acetyl-P-aminophenol; APAP) is an antipyretic and analgesic medication known as paracetamol. Read More

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http://dx.doi.org/10.1007/s11255-018-2053-0DOI Listing
April 2019
4 Reads

Shikonin Attenuates Acetaminophen-Induced Hepatotoxicity by Upregulation of Nrf2 through Akt/GSK3β Signaling.

Molecules 2018 Dec 29;24(1). Epub 2018 Dec 29.

Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model Systems, Guangdong Pharmaceutical University, Guangzhou 510006, China.

Acetaminophen (APAP) overdose-induced acute liver damage is mostly due to overwhelmingly increased oxidative stress. Nuclear factor-erythroid 2-related factor2 (Nrf2) plays an important role in alleviating APAP hepatic toxicity. Shikonin (SHK) enhances Nrf2 in multiple lines of normal cells. Read More

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http://dx.doi.org/10.3390/molecules24010110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337349PMC
December 2018
6 Reads
2.416 Impact Factor

Increased susceptibility to oxidative stress-induced toxicological evaluation by genetically modified nrf2a-deficient zebrafish.

J Pharmacol Toxicol Methods 2019 Mar - Apr;96:34-45. Epub 2018 Dec 27.

Department of Systems Pharmacology, Mie University Graduate School of Medicine, Mie, Japan; Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Mie, Japan; Mie University Medical Zebrafish Research Center, Mie, Japan; Department of Bioinformatics, Mie University Life Science Research Center, Mie, Japan; Department of Omics Medicine, Mie University Industrial Technology Innovation Institute, Mie, Japan.

Introduction: Oxidative stress plays an important role in drug-induced toxicity. Oxidative stress-mediated toxicities can be detected using conventional animal models but their sensitivity is insufficient, and novel models to improve susceptibility to oxidative stress have been researched. In recent years, gene targeting methods in zebrafish have been developed, making it possible to generate homozygous null mutants. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10568719173055
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http://dx.doi.org/10.1016/j.vascn.2018.12.006DOI Listing
December 2018
18 Reads

Victims of chemical terrorism, a family of four who were exposed to sulfur mustard.

Toxicol Lett 2019 Mar 17;303:9-15. Epub 2018 Dec 17.

University of Health Sciences, Dept. of Medical CBRN Defense, 06010, Etlik, Ankara, Turkey.

Sulfur mustard (SM) was responsible for more than 80% of all documented chemical casualties during the Great War. Recent literature on clinic picture of SM exposure remained so limited with the sporadic cases who were accidentally exposed to SM especially either in Western Europe or China. We reported a Syrian family of four who became victims of chemical terrorism due to SM exposure and we described the detailed clinical course of the family including the medical history, initial symptomatology, clinical examination, hematological data, and initial treatment in the first 48 hours after exposure at Kilis State Hospital, Turkey. Read More

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http://dx.doi.org/10.1016/j.toxlet.2018.12.006DOI Listing
March 2019
9 Reads

First aid interventions by laypeople for acute oral poisoning.

Cochrane Database Syst Rev 2018 12 19;12:CD013230. Epub 2018 Dec 19.

Centre for Evidence-Based Practice (CEBaP), Belgian Red Cross, Motstraat 42, Mechelen, Belgium, 2800.

Background: Oral poisoning is a major cause of mortality and disability worldwide, with estimates of over 100,000 deaths due to unintentional poisoning each year and an overrepresentation of children below five years of age. Any effective intervention that laypeople can apply to limit or delay uptake or to evacuate, dilute or neutralize the poison before professional help arrives may limit toxicity and save lives.

Objectives: To assess the effects of pre-hospital interventions (alone or in combination) for treating acute oral poisoning, available to and feasible for laypeople before the arrival of professional help. Read More

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http://doi.wiley.com/10.1002/14651858.CD013230
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http://dx.doi.org/10.1002/14651858.CD013230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438817PMC
December 2018
12 Reads

Small Heterodimer Partner Regulates Circadian Cytochromes p450 and Drug-Induced Hepatotoxicity.

Theranostics 2018 22;8(19):5246-5258. Epub 2018 Oct 22.

Research Center for Biopharmaceutics and Pharmacokinetics, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou, China.

The role of small heterodimer partner (SHP) in regulation of xenobiotic detoxification remains elusive. Here, we uncover a critical role for SHP in circadian regulation of cytochromes P450 (CYPs) and drug-induced hepatotoxicity. The mRNA and protein levels of CYPs in the livers of wild-type and SHP mice were measured by quantitative real-time polymerase chain reaction and Western blotting, respectively. Read More

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http://www.thno.org/v08p5246.htm
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http://dx.doi.org/10.7150/thno.28676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276094PMC
October 2018
14 Reads

Acetaminophen cytotoxicity in HepG2 cells is associated with a decoupling of glycolysis from the TCA cycle, loss of NADPH production, and suppression of anabolism.

Arch Toxicol 2019 Feb 14;93(2):341-353. Epub 2018 Dec 14.

Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.

Acetaminophen (APAP) is one of the most commonly used analgesics worldwide, and overdoses are associated with lactic acidosis, hepatocyte toxicity, and acute liver failure due to oxidative stress and mitochondrial dysfunction. Hepatoma cell lines typically lack the CYP450 activity to generate the reactive metabolite of APAP observed in vivo, but are still subject to APAP cytotoxicity. In this study, we employed metabolic profiling and isotope labelling approaches to investigate the metabolic impact of acute exposure to cytotoxic doses of APAP on the widely used HepG2 cell model. Read More

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http://dx.doi.org/10.1007/s00204-018-2371-0DOI Listing
February 2019
9 Reads

Protective effects of Cinnamomum zeylanicum L. (Darchini) in acetaminophen-induced oxidative stress, hepatotoxicity and nephrotoxicity in mouse model.

Biomed Pharmacother 2019 Jan 28;109:2285-2292. Epub 2018 Nov 28.

Institute of Microbiology, University of Agriculture, Faisalabad, 38040, Pakistan.

Cinnamomum zeylanicum, a widely used spice and flavor, is used in the treatment and prevention of many diseases. In the current study, Balb/c mice were pretreated with cinnamon bark aqueous extract (200 mg/kg/day i.g. Read More

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http://dx.doi.org/10.1016/j.biopha.2018.11.123DOI Listing
January 2019
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Dimethyl fumarate ameliorates acetaminophen-induced hepatic injury in mice dependent of Nrf-2/HO-1 pathway.

Life Sci 2019 Jan 11;217:251-260. Epub 2018 Dec 11.

Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address:

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. Read More

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http://dx.doi.org/10.1016/j.lfs.2018.12.013DOI Listing
January 2019
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The diagnostic role of miR-122 in drug-induced liver injury: A systematic review and meta-analysis.

Medicine (Baltimore) 2018 Dec;97(49):e13478

School of Graduates, Tianjin Medical University.

Background: Drug-induced liver injury (DILI) is a potentially severe adverse drug reaction especially in susceptible patients. But there are no sensitive or specific parameters to detecting DILI. The specific expression of miR-122 in the liver has been a hotspot in the evaluation of hepatic toxicity due to its high stability and sensitivity. Read More

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http://dx.doi.org/10.1097/MD.0000000000013478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310488PMC
December 2018

Pharmacotherapy for patent ductus arteriosus closure.

Authors:
John M Ferguson

Congenit Heart Dis 2019 Jan 11;14(1):52-56. Epub 2018 Dec 11.

Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee.

Even though up to 60% of premature infants less than 28 weeks gestation develop persistent patent ductus arteriosus (PDA), there remains controversy regarding if, when, and how to close the PDA. Failure to close the PDA has been associated with significant morbidity but no cause-and-effect has been proven for short-term or long-term outcomes in modern times. Surgical closure has the advantage of eliminating the PDA, but short-term complications and long-term adverse outcomes are worrisome. Read More

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http://dx.doi.org/10.1111/chd.12715DOI Listing
January 2019
5 Reads

Acute and chronic effects of paracetamol exposure on Daphnia magna: how oxidative effects may modulate responses at distinct levels of organization in a model species.

Environ Sci Pollut Res Int 2019 Feb 1;26(4):3320-3329. Epub 2018 Dec 1.

Departamento de Biologia, Universidade de Aveiro, Campus de Santiago, 3810-193, Aveiro, Portugal.

The modern usage of pharmaceutical drugs has led to a progressive increase in their presence and environment concentrations, particularly in the aquatic compartment which is the most common final dumping location for this specific class of chemicals. These substances, due to their chemical and biological properties, can exert mostly uncharacterized toxic effects to non-target aquatic species, given the diverse pathways they activate, and the large number of putative targets in the wild. Among drugs in the environment, paracetamol assumes a leading role, considering its widespread therapeutic use and consequently, environmental presence. Read More

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http://dx.doi.org/10.1007/s11356-018-3788-yDOI Listing
February 2019
3 Reads

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives.

J Clin Transl Res 2018 28;4(1). Epub 2018 May 28.

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, US.

Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. Read More

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http://dx.doi.org/10.18053/jctres.04.201801.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261533PMC
May 2018
6 Reads

Acetaminophen absorption and metabolism in an intestine/liver microphysiological system.

Chem Biol Interact 2019 Feb 26;299:59-76. Epub 2018 Nov 26.

Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Zip Code 13083-970, Campinas, São Paulo, Brazil.

This study describes the characterization of pharmacokinetic (PK) properties of acetaminophen (APAP) in the Two-Organ-Chip platform (2-OC), a two-chamber device able to cultivate 3D tissues under flow. The APAP intestinal absorption and hepatic metabolism were emulated by human intestine and liver equivalents respectively. The intestinal barrier was produced using Caco-2 and HT-29 cells. Read More

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http://dx.doi.org/10.1016/j.cbi.2018.11.010DOI Listing
February 2019
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Therapeutic Potential of Plants and Plant Derived Phytochemicals against Acetaminophen-Induced Liver Injury.

Int J Mol Sci 2018 Nov 28;19(12). Epub 2018 Nov 28.

Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, PO Box # 17666, United Arab Emirates University, Al Ain 17666, UAE.

Acetaminophen (APAP), which is also known as paracetamol or -acetyl--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. Read More

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http://dx.doi.org/10.3390/ijms19123776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321362PMC
November 2018
1 Read
2.862 Impact Factor