37,241 results match your criteria Drug-Induced Hepatotoxicity


The application of cytokeratin-18 as a biomarker for drug-induced liver injury.

Arch Toxicol 2021 Jul 29. Epub 2021 Jul 29.

Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.

Drug-induced liver injury (DILI) is a frequent and dangerous adverse effect faced during preclinical and clinical drug therapy. DILI is a leading cause of candidate drug attrition, withdrawal and in clinic, is the primary cause of acute liver failure. Traditional diagnostic markers for DILI include alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Read More

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Assessing Toxicity in Drug Trials in Liver Disease.

Authors:
Morris Sherman

Semin Liver Dis 2021 Aug 8;41(3):277-284. Epub 2021 Mar 8.

Research Administration, University Health Network, Toronto, Canada.

Since the early trials in viral hepatitis, more and more new drugs are being tested for use in various liver diseases. Since drug hepatotoxicity is a major cause of drugs under investigation not making it to market, the assessment of drug-induced liver injury in clinical trials of new drugs is crucial. This review will focus on the systems that are used to assess drug-induced liver injury in clinical trials and will discuss how some of these criteria are inappropriate or inaccurate in this function together with suggestions for improvement. Read More

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Metabolic map of the antiviral drug podophyllotoxin provides insights into hepatotoxicity.

Xenobiotica 2021 Jul 28:1-36. Epub 2021 Jul 28.

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Podophyllotoxin (POD) is a natural compound with antiviral and anticancer activities. The purpose of the present study was to determine the metabolic map of POD in vitro and in vivo.Mouse and human liver microsomes were employed to identify POD metabolites in vitro and recombinant drug-metabolizing enzymes were used to identify the mono-oxygenase enzymes involved in POD metabolism. Read More

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Using an Automated Algorithm to Identify Potential Drug-Induced Liver Injury Cases in a Pharmacovigilance Database.

Adv Ther 2021 Jul 28. Epub 2021 Jul 28.

Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center, Princeton, NJ, 08540, USA.

Introduction: Drug-induced liver injury (DILI) is the most frequent cause of acute liver failure in North America and Europe, but it is often missed because of unstandardized diagnostic methods and criteria. This study aimed to develop and validate an automated algorithm to identify potential DILI cases in routine pharmacovigilance (PV) activities.

Methods: Post-marketing hepatic adverse events reported for a potentially hepatotoxic drug in a global PV database from 19 March 2017 to 18 June 2018 were assessed manually and with the automated algorithm. Read More

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A 3D cell printing-fabricated HepG2 liver spheroid model for high-content quantification of drug-induced liver toxicity.

Biomater Sci 2021 Jul 27. Epub 2021 Jul 27.

College of Pharmacy, Seoul National University, Seoul 08826, South Korea.

3D spheroid cultures are attractive candidates for application in in vitro drug-induced hepatotoxicity testing models to improve the reliability of biological information obtainable from a simple 2D culture model. Various 3D spheroid culture models exist for hepatotoxicity screening, but quantitative assays of spheroid response in situ are still challenging to achieve with the current 3D liver toxicity platforms. In this study, we developed a 3D printing-based HepG2 liver spheroid culture model for in situ quantitative evaluation and high-content monitoring of drug-induced hepatotoxicity. Read More

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Vitamin D modulates hepatic microRNAs and mitigates tamoxifen-induced steatohepatitis in female rats.

Fundam Clin Pharmacol 2021 Jul 27. Epub 2021 Jul 27.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Background: Tamoxifen (TAM) is a life-saving and cost-effective drug widely used in the prevention and treatment of breast cancer. However, the adverse effects of tamoxifen can lead to non-adherence and poor patient outcomes. Therefore, exploring novel strategies to improve TAM safety profile is crucial. Read More

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Warfarin-induced Stevens-Johnson syndrome with severe liver injury.

J Int Med Res 2021 Jul;49(7):3000605211033196

Department of Dermatology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening mucocutaneous disease that is predominantly drug-induced. Warfarin is the most commonly used drug for long-term anti-coagulant therapy; however, warfarin-induced SJS/TEN is seldom reported. In this study, we presented the case of a 61-year-old man who developed SJS after receiving multiple-drug therapy following aortic valve replacement surgery. Read More

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Protective role of microRNA-31 in acetaminophen-induced liver injury: a negative regulator of c-Jun N-terminal kinase (JNK) signaling pathway.

Cell Mol Gastroenterol Hepatol 2021 Jul 23. Epub 2021 Jul 23.

Department of Liver Surgery and Liver Transplantation Center, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.

Background & Aims: Sustained JNK activation plays a major role in drug-induced liver injury (DILI). Stress-responsive microRNA-31 (miR-31) has been implicated in regulating different cellular damage, and JNK activation could induce miR-31 expression. However, the regulatory role of miR-31 in DILI has not been previously studied. Read More

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Herb-induced liver injury: Systematic review and meta-analysis.

World J Clin Cases 2021 Jul;9(20):5490-5513

Department of Clinical Gastroenterology, Universidade de Caxias do Sul, Caxias do Sul 95070-560, RS, Brazil.

Background: The use of herbal supplements and alternative medicines has been increasing in the last decades. Despite popular belief that the consumption of natural products is harmless, herbs might cause injury to various organs, particularly to the liver, which is responsible for their metabolism in the form of herb-induced liver injury (HILI).

Aim: To identify herbal products associated with HILI and describe the type of lesion associated with each product. Read More

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Ulinastatin protects against acetaminophen-induced liver injury by alleviating ferroptosis via the SIRT1/NRF2/HO-1 pathway.

Am J Transl Res 2021 15;13(6):6031-6042. Epub 2021 Jun 15.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, Shaanxi, People's Republic of China.

Acetaminophen (APAP) overdose has been considered responsible for the drug-induced liver injury for many years. Ferroptosis is defined as an iron-dependent form of cell death associated with lipid peroxide accumulation. Ferroptosis is involved in APAP-induced acute liver failure, and UTI is an effective drug treatment for acute liver failure. Read More

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Herb-drug interactions and toxicity: Underscoring potential mechanisms and forecasting clinically relevant interactions induced by common phytoconstituents via data mining and computational approaches.

Food Chem Toxicol 2021 Jul 19:112432. Epub 2021 Jul 19.

Department of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Réduit, Mauritius. Electronic address:

Herbals in the form of medicine are employed extensively around the world. Herbal and conventional medicine combination is a potentially dangerous practice mainly in comorbid, hepato insufficient and frail patients leading to perilous herb-drug interactions (HDI) and toxicity. This study features potential HDI of 15 globally famous plant species through data mining and computational methods. Read More

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Use of N-Acetylcysteine for Clozapine-Induced Acute Liver Injury: A Case Report and Literature Review.

J Pharm Pract 2021 Jul 20:8971900211034007. Epub 2021 Jul 20.

Department of Pharmacy, Columbia University Irving Medical Center, NewYork-Presbyterian Hospital, New York, NY, USA.

To report a case of clozapine-induced hepatotoxicity managed with intravenous (IV) N-acetylcysteine (NAC) and summarize the available literature. A 46-year-old woman with history of bipolar disorder with psychotic features presented to the intensive care unit with asterixis and elevations in liver enzymes. The patient had been initiated on risperidone, clozapine, and lithium approximately 1 month prior to admission. Read More

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Hepatoprotective Impact of Ghrelin against Cyclophosphamide-Induced Toxicity in the Male Mice.

Drug Res (Stuttg) 2021 Jul 19. Epub 2021 Jul 19.

Department of Anatomical Sciences and Pathology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.

Background: Despite its vast spectrum of clinical usage, cyclophosphamide (CP) exerts many adverse impacts, including hepatotoxicity. Antioxidant properties of ghrelin might protect the liver from CP-induced toxicity. The current study aimed to assess the protective impacts of ghrelin on CP-induced liver toxicity. Read More

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A New Paradigm for Safety Data Signal Detection and Evaluation Using Open-Source Software Created by an Interdisciplinary Working Group.

Ther Innov Regul Sci 2021 Jul 19. Epub 2021 Jul 19.

Gilead Sciences, Foster City, CA, USA.

Techniques to evaluate large amounts of safety data continue to evolve based on a greater understanding of how the brain processes visual information and the advancement of programing tools. The Interactive Safety Graphics Task Force of the American Statistical Association Biopharmaceutical Safety Working Group has assembled a multidisciplinary team of experts in a variety of domains to develop the next generation of open-source visual analytical tools for safety data based on these advances. The multidisciplinary approach resulted in the rapid development of the first tool, a novel interactive version of the familiar Evaluation of Drug-Induced Serious Hepatotoxicity (eDISH) graphic along with a unique clinical workflow to guide the reviewer through the data analysis. Read More

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Prediction of Alternative Drug-Induced Liver Injury Classifications Using Molecular Descriptors, Gene Expression Perturbation, and Toxicology Reports.

Front Genet 2021 1;12:661075. Epub 2021 Jul 1.

Institute of Computer Science, University of Bialystok, Białystok, Poland.

Drug-induced liver injury (DILI) is one of the primary problems in drug development. Early prediction of DILI, based on the chemical properties of substances and experiments performed on cell lines, would bring a significant reduction in the cost of clinical trials and faster development of drugs. The current study aims to build predictive models of risk of DILI for chemical compounds using multiple sources of information. Read More

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Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypes.

Arch Toxicol 2021 Jul 17. Epub 2021 Jul 17.

Unidad de Hepatología Experimental, Health Research Institute La Fe, Valencia, Spain.

Drug-induced liver injury (DILI) is an adverse toxic hepatic clinical reaction associated to the administration of a drug that can occur both at early clinical stages of drug development, as well after normal clinical usage of approved drugs. Because of its unpredictability and clinical relevance, it is of medical concern. Three DILI phenotypes (hepatocellular, cholestatic, and mixed) are currently recognized, based on serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) values. Read More

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Drug-induced liver injury in Australia, 2009-2020: the increasing proportion of non-paracetamol cases linked with herbal and dietary supplements.

Med J Aust 2021 Jul 17. Epub 2021 Jul 17.

AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW.

Objective: To compare the characteristics and outcomes of drug-induced liver injury (DILI) caused by paracetamol and non-paracetamol medications, particularly herbal and dietary supplements.

Design: Retrospective electronic medical record data analysis.

Setting, Participants: Adults admitted with DILI to the Gastroenterology and Liver Centre at the Royal Prince Alfred Hospital, Sydney (a quaternary referral liver transplantation centre), 2009-2020. Read More

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Unusual Recurrence of Antituberculosis Drug-Induced Hepatotoxicity in Children: A Case Series.

Am J Case Rep 2021 Jul 16;22:e930828. Epub 2021 Jul 16.

Department of Child Health, Dr. Hasan Sadikin General Hospital, Bandung, West Java, Indonesia.

BACKGROUND Antituberculosis drug-induced hepatotoxicity (ADIH) is a possible adverse event of antitubercular treatment. There are still no official guidelines for ADIH management in children. Recurrent ADIH is infrequently reported. Read More

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Validation of Unani concept of (drug substitution) by physicochemical standardization and hepatoprotective activity of Linn. and its substitute Rosc. in albino Wistar rats.

J Complement Integr Med 2021 Jul 15. Epub 2021 Jul 15.

Regional Research Institute of Unani Medicine (RRIUM), CCRUM, Ministry of AYUSH, Govt. of India, Chennai, India.

Objectives: To validate the concept of (drug substitution) by evaluation of physicochemical standardization and hepatoprotective activity of & its substitute, in albino Wistar rats.

Methods: Physicochemical standardization by estimation of moisture content, ash values and extractive values were carried out using standard methods. Hepatotoxicity was induced in albino Wistar rats using CCl 1 mL/kg s. Read More

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The Study on the Mechanism of Hugan Tablets in Treating Drug-Induced Liver Injury Induced by Atorvastatin.

Front Pharmacol 2021 28;12:683707. Epub 2021 Jun 28.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.

Atorvastatin is a widely used lipid-lowering drug in the clinic. Research shows that taking long-term atorvastatin has the risk of drug-induced liver injury (DILI) in most patients. Hugan tablets, a commonly used drug for liver disease, can effectively lower transaminase and protect the liver. Read More

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A possible interaction between favipiravir and methotrexate: Drug-induced hepatotoxicity in a patient with osteosarcoma.

J Oncol Pharm Pract 2021 Jul 13:10781552211031304. Epub 2021 Jul 13.

Department of Medical Oncology, Gazi University, Ankara, Turkey.

Introduction: Favipiravir is an antiviral agent that is recently used for SARS-CoV2 infection. The drug-drug interactions of favipiravir especially with chemotherapeutic agents in a patient with malignancy are not well known.

Case Report: The patient diagnosed with metastatic osteosarcoma was given high dose methotrexate treatment, and favipiravir was started on the third day of the treatment with suspicion of SARS-CoV2 infection. Read More

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LXR-Mediated Regulation of Marine-Derived Piericidins Aggravates High-Cholesterol Diet-Induced Cholesterol Metabolism Disorder in Mice.

J Med Chem 2021 Jul 12;64(14):9943-9959. Epub 2021 Jul 12.

NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.

Reported as two antirenal cell carcinoma (RCC) drug candidates, marine-derived compounds piericidin A (PA) and glucopiericidin A (GPA) exhibit hepatotoxicity in renal carcinoma xenograft mice. Proteomics and transcriptomics reveal the hepatotoxicity related with cholesterol disposition since RCC is characterized by cholesterol accumulation. PA/GPA aggravate hepatotoxicity in high-cholesterol diet (HCD)-fed mice while exhibiting no toxicity in chow diet-fed mice. Read More

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Genetic and Functional Evaluation of the Role of FOXO1 in Antituberculosis Drug-Induced Hepatotoxicity.

Evid Based Complement Alternat Med 2021 19;2021:3185874. Epub 2021 Jun 19.

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: The accumulation of the hepatotoxic substance protoporphyrin IX (PPIX) induced by aminolevulinate synthase 1 (ALAS1) activation is one of the important mechanisms of antituberculosis drug-induced hepatotoxicity (ATDH). Forkhead box protein O1 (FOXO1) may activate ALAS1 transcription. However, little is known about their roles in ATDH; we performed a study to determine the association between polymorphisms in the two genes and ATDH susceptibility. Read More

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Clinical efficacy and security of glycyrrhizic acid preparation in the treatment of anti-SARS-CoV-2 drug-induced liver injury: a protocol of systematic review and meta-analysis.

BMJ Open 2021 07 9;11(7):e051484. Epub 2021 Jul 9.

Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China

Introduction: COVID-19 is a highly infectious acute pneumonia. Glycyrrhizic acid preparation (GAP) has been found to have hepatoprotective and antiviral effects, but there is no supporting evidence on its efficacy and security for patients with COVID-19.

Methods And Analysis: The systematic review methods will be defined by Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Read More

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Therapeutic advancement of simvastatin-loaded solid lipid nanoparticles (SV-SLNs) in treatment of hyperlipidemia and attenuating hepatotoxicity, myopathy and apoptosis: Comprehensive study.

Biomed Pharmacother 2021 Jul 8;139:111494. Epub 2021 May 8.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Fayoum University, Fayoum, Egypt. Electronic address:

This study set out to optimize simvastatin (SV) in lipid nanoparticles (SLNs) to improve bioavailability, efficacy and alleviate adverse effects. Simvastatin-loaded solid lipid nanoparticles (SV-SLNs) were prepared by hot-melt ultrasonication method and optimized by box-Behnken experimental design. Sixty Wister albino rats were randomly assigned into six groups and treated daily for 16 weeks: control group, the group fed with 20 g of high-fat diet (HFD), group treated with vehicle (20 mg/kg, P. Read More

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Acute Hepatic Dysfunction Related to Chronic Acetaminophen Administration.

J Pediatr Pharmacol Ther 2021 28;26(5):497-501. Epub 2021 Jun 28.

Toxicity related to acetaminophen is most encountered with the acute ingestion of large doses. However, toxicity may also result from chronic ingestion, even when recommended doses are administered over a prolonged period of time. We present the case of a 20-month-old female toddler who received therapeutic recommended doses of acetaminophen (oral or intravenous) following multiple surgical interventions for treatment of a tracheo-esophageal fistula following ingestion of a button battery. Read More

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Severe drug-induced liver injury caused by levetiracetam - A case report and review of the literature.

Epilepsy Behav Rep 2021 8;16:100464. Epub 2021 Jun 8.

Department of Neurology, Evangelisches Klinikum Bethel, University Hospital OWL of the University Bielefeld, Campus Bielefeld-Bethel, Bielefeld, Germany.

Levetiracetam (LEV) is a broad-spectrum, second-generation anti-seizure medication, which has quickly become one of the most commonly prescribed drugs for people with epielpsy due to its good tolerability, rapid up-dosing capability, with both parenteral and enteral routes of administration. Considering the frequent prescriptions and predominant excretion by the kidney with minimal hepatic metabolism, severe liver injury is very rarely a complication associated with LEV. An analysis of this reported case and further published cases was performed with respect to indication, relevant previous liver diseases, concomitant medication, and both the dosage as well as the duration of LEV when drug-induced liver injury (DILI) was noted. Read More

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ameliorated 7,12-Dimethylbenz[a]anthracene-induced upregulations of Ki67 and multidrug resistance 1 genes in rats.

Int J Health Sci (Qassim) 2021 May-Jun;15(3):26-33

Department of Anatomy, Faculty of Basic Medical Sciences, Ekiti State University, Ado-Ekiti, Ekiti State, Nigeria.

Objectives: (MO) and (MS) are plants of ethnomedicinal importance. We evaluated the effects of MOF6 (extracted from MO leaves) and MSF1 (extracted from MS suckers) on immunomodulations of Ki67 (proliferation biomarker) and multidrug resistance 1 (MDR1) genes in the liver of rats in 7,12-Dimethylbenz[a]anthracene (DMBA)-induced hepatotoxicity and mutagenesis to determine their antiproliferation, anti-drug resistance, and anticancer potentials.

Methods: Forty-five adult male rats were randomly divided into nine groups ( = 5). Read More

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Glabridin attenuates paracetamol-induced liver injury in mice via CYP2E1-mediated inhibition of oxidative stress.

Drug Chem Toxicol 2021 Jul 7:1-9. Epub 2021 Jul 7.

PK-PD, Toxicology and Formulation Division, CSIR-Indian Institute of Integrative Medicine, Jammu, Jammu and Kashmir, India.

CYP2E1 plays a crucial role in the bio-activation of toxic substances leading to liver damage. In this context, CYP2E1 converts paracetamol (PCM) to N-acetyl-p-benzoquinone imine (NAPQI), which is prone to cause hepatotoxicity. Hence, we aimed to explore the protective effect of glabridin on widely used PCM-induced liver injury model in the present study and, after that, correlated with the role of CYP2E1 toward its efficacy. Read More

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[Hepatotoxicity probably associated with gabapentin].

Rev Med Inst Mex Seguro Soc 2021 Jun 14;59(2):157-162. Epub 2021 Jun 14.

Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, Hospital de Especialidades "Dr. Bernardo Sepúlveda Gutiérrez", Departamento de Anestesiología. Ciudad de México, México.

Background: Gabapentin is an anticonvulsant medication used as an adjuvant in the treatment of neuropathic pain; few cases have been reported in which it causes acute liver injury.

Clinical Case: 56-year-old male patient with a history of chronic kidney disease on hemodialysis and narrowing of the spinal canal under treatment with gabapentin, who presented acute liver injury probably secondary to a dose of gabapentin; however, it remitted with the suspension of said drug.

Conclusion: Gabapentin lacks liver metabolism; the mechanism by which it produces liver injury is still unknown; however, there are reports of hepatotoxicity associated with its administration, so its use must be individualized for each patient. Read More

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