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    6594 results match your criteria Drug-Induced Hepatotoxicity

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    Baseline HBV load increases the risk of anti-tuberculous drug-induced hepatitis flares in patients with tuberculosis.
    J Huazhong Univ Sci Technolog Med Sci 2017 Feb 22;37(1):105-109. Epub 2017 Feb 22.
    Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
    Hepatitis associated anti-tuberculous treatment (HATT) has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus (HBV). Therefore, we evaluated the factors related to the severity of adverse effects during HATT, especially those associated with liver failure. A retrospective study was carried out at Tongji Hospital from 2007 to 2012. Read More

    Psychotropic drugs and liver disease: A critical review of pharmacokinetics and liver toxicity.
    World J Gastrointest Pharmacol Ther 2017 Feb;8(1):26-38
    Diogo Telles-Correia, António Barbosa, Helena Cortez-Pinto, Faculty of Medicine, University of Lisbon, 1649-028 Lisbon, Portugal.
    The liver is the organ by which the majority of substances are metabolized, including psychotropic drugs. There are several pharmacokinetic changes in end-stage liver disease that can interfere with the metabolization of psychotropic drugs. This fact is particularly true in drugs with extensive first-pass metabolism, highly protein bound drugs and drugs depending on phase I hepatic metabolic reactions. Read More

    (1)H NMR-based serum metabolomics reveals erythromycin-induced liver toxicity in albino Wistar rats.
    J Pharm Bioallied Sci 2016 Oct-Dec;8(4):327-334
    Centre of Biomedical Research, Sanjay Gandhi Post Graduate Institute of Medical Sciences Campus, Lucknow, Uttar Pradesh, India.
    Introduction: Erythromycin (ERY) is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. Read More

    Isolation and Expansion of Human Pluripotent Stem Cell-derived Hepatic Progenitor Cells by Growth Factor Defined Serum-free Culture Conditions.
    Exp Cell Res 2017 Feb 16. Epub 2017 Feb 16.
    Laboratory of Stem Cell Cultures, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan. Electronic address:
    Limited growth potential, narrow ranges of sources, and difference in variability and functions from batch to batch of primary hepatocytes cause a problem for predicting drug-induced hepatotoxicity during drug development. Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells in vitro are expected as a tool for predicting drug-induced hepatotoxicity. Several studies have already reported efficient methods for differentiating hPSCs into hepatocyte-like cells, however its differentiation process is time-consuming, labor-intensive, cost-intensive, and unstable. Read More

    Acute temozolomide induced liver injury : Mixed type hepatocellular and cholestatic toxicity.
    Acta Gastroenterol Belg 2016 Sep-Dec;79(4):487-489
    Temozolomide (TMZ) is an oral imidazotetrazine methylating agent which is used for the treatment of glioblastoma multiforme (GBM). We report a case of acute hepatotoxicity in a 53-year old male patient after administration of TMZ for GBM. He had fatigue, nausea, anorexia and jaundice. Read More

    Cell Imaging Counting as a Novel Ex Vivo Approach for Investigating Drug-Induced Hepatotoxicity in Zebrafish Larvae.
    Int J Mol Sci 2017 Feb 8;18(2). Epub 2017 Feb 8.
    Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, O & N II Herestraat 49-box 824, 3000 Leuven, Belgium.
    Drug-induced liver injury (DILI) is the most common reason for failures during the drug development process and for safety-related withdrawal of drugs from the pharmaceutical market. Therefore, having tools and techniques that can detect hepatotoxic properties in drug candidates at an early discovery stage is highly desirable. In this study, cell imaging counting was used to measure in a fast, straightforward, and unbiased way the effect of paracetamol and tetracycline, (compounds known to cause hepatotoxicity in humans) on the amount of DsRed-labeled hepatocytes recovered by protease digestion from Tg(fabp10a:DsRed) transgenic zebrafish. Read More

    Evaluation of transcriptomic signature as a valuable tool to study drug-induced cholestasis in primary human hepatocytes.
    Arch Toxicol 2017 Feb 10. Epub 2017 Feb 10.
    KaLy-Cell, 20A rue du Général Leclerc, 67115, Plobsheim, France.
    Primary human hepatocyte (PHH) sandwich cultures from five different donors were daily exposed to cyclosporine A (CsA), ibuprofen (IBU), chlorpromazine (CPZ), amiodarone (AMI) and paracetamol (APAP) at their respective Cmax (total) for short-term (1-3 days) and long-term treatment (14 days). Whole genome mRNA profiles (34,693 genes in total) were conducted using an Illumina microarray platform. The impact of compound treatments on gene signatures involved in liver differentiation, cholestasis and in bile acid homeostasis was evaluated. Read More

    Associations of Gender and a Proxy of female Menopausal status with Histological Features of Drug-Induced Liver Injury.
    Liver Int 2017 Feb 5. Epub 2017 Feb 5.
    Laboratory of Pathology, National Cancer Institute, Bethesda, MD.
    Background And Aim: Gender and menopause may contribute to type and severity of drug-induced liver injury (DILI) by influencing host responses to injury. The aim of this study was to assess the associations of gender and female age 50 [a proxy of menopause] with histologic features of liver injury in 212 adults enrolled in the Drug-Induced Liver Injury Network (DILIN) registry METHODS: All participants had a causality score of at least 'probable', a liver biopsy within 30 days of DILI onset, and no prior chronic liver disease. Biochemical and histologic injury types were classified as hepatocellular or cholestatic/mixed injury. Read More

    A Comparative Analysis of Drug-Induced Hepatotoxicity in Clinically Relevant Situations.
    PLoS Comput Biol 2017 Feb 2;13(2):e1005280. Epub 2017 Feb 2.
    Institute of Applied Microbiology (iAMB), Aachen Biology and Biotechnology (ABBt), RWTH Aachen University, Worringerweg 1, Aachen, Germany.
    Drug-induced toxicity is a significant problem in clinical care. A key problem here is a general understanding of the molecular mechanisms accompanying the transition from desired drug effects to adverse events following administration of either therapeutic or toxic doses, in particular within a patient context. Here, a comparative toxicity analysis was performed for fifteen hepatotoxic drugs by evaluating toxic changes reflecting the transition from therapeutic drug responses to toxic reactions at the cellular level. Read More

    In Silico Identification of Proteins Associated with Drug-Induced Liver Injury Based on the Prediction of Drug-Target Interactions.
    Mol Inform 2017 Feb 1. Epub 2017 Feb 1.
    Institute of Biomedical Chemistry 10 building 8, Pogodinskaya str., 119121, Moscow, Russia.
    Drug-induced liver injury (DILI) is the leading cause of acute liver failure as well as one of the major reasons for drug withdrawal from clinical trials and the market. Elucidation of molecular interactions associated with DILI may help to detect potentially hazardous pharmacological agents at the early stages of drug development. The purpose of our study is to investigate which interactions with specific human protein targets may cause DILI. Read More

    Protective effect of Curcuma longa L. extract on CCl4-induced acute hepatic stress.
    BMC Res Notes 2017 Feb 1;10(1):77. Epub 2017 Feb 1.
    Department of Pharmacology and New Drug Development Institute, Chonbuk National University Medical School, Jeonju, Chonbuk, 561-180, Republic of Korea.
    Background: The Curcuma longa L. (CLL) rhizome has long been used to treat patients with hepatic dysfunction. CLL is a member of the ginger family of spices that are widely used in China, India, and Japan, and is a common spice, coloring, flavoring, and traditional medicine. Read More

    Prediction of drug-induced liver injury using keratinocytes.
    J Appl Toxicol 2017 Jan 31. Epub 2017 Jan 31.
    School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
    Drug-induced liver injury (DILI) is one of the most common adverse drug reactions. DILI is often accompanied by skin reactions, including rash and pruritus. However, it is still unknown whether DILI-associated genes such as S100 calcium-binding protein A and interleukin (IL)-1β are involved in drug-induced skin toxicity. Read More

    Transcriptional, functional and mechanistic comparisons of stem cell-derived hepatocytes, HepaRG cells and 3D human hepatocyte spheroids as predictive in vitro systems for drug-induced liver injury.
    Drug Metab Dispos 2017 Jan 30. Epub 2017 Jan 30.
    Karolinska Institutet.
    Reliable and versatile hepatic in vitro systems for the prediction of drug pharmacokinetics and toxicity are essential constituents of preclinical safety assessment pipelines for new medicines. Here, we compared three emerging cell systems, hepatocytes derived from induced pluripotent stem cells (hiPS-Hep), HepaRG cells and 3D primary human hepatocyte (PHH) spheroids at transcriptional and functional levels in a multi-center study to evaluate their potential as predictive models for drug-induced hepatotoxicity. Transcriptomic analyses revealed widespread gene expression differences between the three cell models, with 8,148 out of 17,462 analyzed genes (47%) being differentially expressed. Read More

    Morphological and immunobiochemical analysis of the liver in L-arginine induced experimental chronic pancreatitis.
    Pancreatology 2017 Jan 21. Epub 2017 Jan 21.
    Department of Pathophysiology, College of Basic Medical Sciences, Dalian Medical University, PR China. No.9, West Section, Lu Shun, Dalian P.C. 116044, Liaoning, PR China. Electronic address:
    Background: Clinical evidence indicates that hepatic abnormalities in patients with chronic pancreatitis are not uncommon. Here we aimed to study the possible association between liver and pancreatic damage in a recently described experimental mouse model of CP.

    Methods: The severity of the damage to pancreas, liver and other organs was assessed by biochemical markers and histopathology. Read More

    Liver Illness and Psychiatric Patients.
    Hepat Mon 2016 Dec 3;16(12):e41564. Epub 2016 Dec 3.
    Service D'hépato-Gastroentérologie, CHU Limoges, 87042 Limoges Cédex, France; INSERM, U850, F-87000 Limoges, Univ Limoges, France.
    Patients with psychiatric disorders are usually more exposed to multiple somatic illnesses, including liver diseases. Specific links are established between psychiatric disorders and alcohol hepatitis, hepatitis B, and hepatitis C in the population as a whole, and specifically in drug abusers. Metabolic syndrome criteria, and associated steatosis or non-alcoholic steato-hepatitis (NASH) are frequent in patients with chronic psychiatric disorders under psychotropic drugs, and should be screened. Read More

    Patient-specific hepatocyte-like cells derived from induced pluripotent stem cells model pazopanib-mediated hepatotoxicity.
    Sci Rep 2017 Jan 25;7:41238. Epub 2017 Jan 25.
    Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Nanos #04-01, Singapore 138669, Republic of Singapore.
    Idiosyncratic drug-induced hepatotoxicity is a major cause of liver damage and drug pipeline failure, and is difficult to study as patient-specific features are not readily incorporated in traditional hepatotoxicity testing approaches using population pooled cell sources. Here we demonstrate the use of patient-specific hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells for modeling idiosyncratic hepatotoxicity to pazopanib (PZ), a tyrosine kinase inhibitor drug associated with significant hepatotoxicity of unknown mechanistic basis. In vitro cytotoxicity assays confirmed that HLCs from patients with clinically identified hepatotoxicity were more sensitive to PZ-induced toxicity than other individuals, while a prototype hepatotoxin acetaminophen was similarly toxic to all HLCs studied. Read More

    Involvement of protoporphyrin IX accumulation in the pathogenesis of isoniazid/rifampicin-induced liver injury: the prevention of curcumin.
    Xenobiotica 2017 Feb;47(2):154-163
    a Institute of Clinical Pharmacy and Pharmacology, Second Xiangya Hospital, Central South University , Changsha , China and.
    Combination of isoniazid (INH) and rifampicin (RFP) causes liver injury frequently among tuberculosis patients. However, mechanisms of the hepatotoxicity are not entirely understood. Protoporphyrin IX (PPIX) accumulation, as an endogenous hepatotoxin, resulting from isoniazid and rifampicin co-therapy (INH/RFP) has been reported in PXR-humanized mice. Read More

    Early Detection of Acute Drug-Induced Liver Injury in Mice by Non-invasive NIR Fluorescence Imaging.
    J Pharmacol Exp Ther 2017 Jan 23. Epub 2017 Jan 23.
    PerkinElmer Inc.
    Hepatocellular and cholestatic forms of drug induced liver injury (DILI) are major reasons for late stage termination of small molecule drug discovery research projects. Biochemical serum markers are limited in their ability to sensitively and specifically detect both of these common DILI forms in preclinical models, and tissue-specific approaches to assessing this are labor intensive, requiring extensive animal dosing, tissue preparation, and pathology assessment. In vivo fluorescent imaging offers non-invasive detection of biological changes detected directly in the livers of living animals. Read More

    Sulforaphane protects against sodium valproate-induced acute liver injury.
    Can J Physiol Pharmacol 2016 Nov 1:1-7. Epub 2016 Nov 1.
    a Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
    Drug-induced hepatotoxicity is one of the most commonly encountered obstacles in the field of medical practice. Sodium valproate (VPA) is among many drugs with reported hepatotoxic effects. Sulforaphane (SFN) is a thiol compound found in wide abundance in cruciferous plants that has numerous reported therapeutic efficacies. Read More

    Zebularine upregulates expression of CYP genes through inhibition of DNMT1 and PKR in HepG2 cells.
    Sci Rep 2017 Jan 23;7:41093. Epub 2017 Jan 23.
    Department of Pharmacology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.
    Drug-induced hepatotoxicity is one of the major reasons cited for drug withdrawal. Therefore, it is of extreme importance to detect human hepatotoxic candidates as early as possible during the drug development process. In this study, we aimed to enhance hepatocyte functions such as CYP gene expression in HepG2 cells, one of the most extensively used cell lines in evaluating hepatotoxicity of chemicals and drugs. Read More

    CORAL: Binary classifications (active/inactive) for drug-induced liver injury.
    Toxicol Lett 2017 Feb 19;268:51-57. Epub 2017 Jan 19.
    Department of Environmental Health Science, Laboratory of Environmental Chemistry and Toxicology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156, Milano, Italy.
    Introduction: The data on human hepatotoxcity (drug-induced liver injury) is extremely important information from point of view of drug discovery. Experimental clinical data on this endpoint is scarce. Experimental way to extend databases on this endpoint is extremely difficult. Read More

    Drug-induced liver injury: Towards early prediction and risk stratification.
    World J Hepatol 2017 Jan;9(1):30-37
    Emanuel Raschi, Fabrizio De Ponti, Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy.
    Drug-induced liver injury (DILI) is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications and agents listed as causing liver damage (http://livertox.nih.gov/). Read More

    Concurrent Inflammation Augments Antimalarial Drugs-Induced Liver Injury in Rats.
    Adv Pharm Bull 2016 Dec 22;6(4):617-625. Epub 2016 Dec 22.
    Pharmacology and Toxicology Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
    Purpose: Accumulating evidence suggests that drug exposure during a modest inflammation induced by bacterial lipopolysaccharide (LPS) might increase the risk of drug-induced liver injury. The current investigation was designed to test if antimalarial drugs hepatotoxicity is augmented in LPS‑treated animals. Methods: Rats were pre-treated with LPS (100 µg/kg, i. Read More

    Clinical and experimental research in antituberculosis drug-induced hepatotoxicity: a review.
    J Integr Med 2017 Jan;15(1):27-36
    School of Biosciences and Technology, VIT University, Vellore-632014, Tamilnadu, India.
    Drug-induced liver injury is the common adverse effect seen in patients receiving antituberculosis drugs (ATDs). There are several risk factors associated with the development of hepatotoxicity in such patients. Though there have been appreciable efforts taken by carrying out studies investigating the efficacy of several natural and synthetic compounds in minimising this effect, the only choice available for clinicians is withdrawal of drugs. Read More

    Contributions of caspase-8 and -9 to liver injury from CYP2E1-produced metabolites of halogenated hydrocarbons.
    Xenobiotica 2017 Jan 12:1-13. Epub 2017 Jan 12.
    a Cardiovascular Pharmacotherapy and Toxicology and.
    1. Drug-induced liver injury is difficult to predict at the pre-clinical stage. This study aimed to clarify the roles of caspase-8 and -9 in CYP2E1 metabolite-induced liver injury in both rats and cell cultures in vitro treated with carbon tetrachloride (CCl4), halothane or sevoflurane. Read More

    ERK Signaling Pathway Plays a Key Role in Baicalin Protection Against Acetaminophen-Induced Liver Injury.
    Am J Chin Med 2017 13;45(1):105-121. Epub 2017 Jan 13.
    * Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
    Acetaminophen (APAP) overdose causes hepatocytes necrosis and acute liver failure. Baicalin (BA), a major flavonoid of Scutellariae radix, has potent hepatoprotective properties in traditional medicine. In the present study, we investigated the protective effects of BA on a APAP-induced liver injury in a mouse model. Read More

    Research Advances on Hepatotoxicity of Herbal Medicines in China.
    Biomed Res Int 2016 18;2016:7150391. Epub 2016 Dec 18.
    China Military Institute of Chinese Medicine, Integrative Medical Center, 302 Military Hospital of China, Beijing 10003, China.
    In general, herbal medicines have been considered as safe by the general public, since they are naturally occurring and have been applied in treatment for over thousands of years. As the use of herbal medicine is rapidly increasing globally, the potential toxicity of herbal drugs, in particular drug-induced liver injury (DILI), has now become a serious medical issue. According to the literature, the authors analyzed and discussed the hepatotoxicity problem of Chinese herbal medicines (CHM), including global overview on herbal-induced liver injury (HILI), current research progress on toxic CHM, diagnosis and treatment of HILI, and modern approaches and technologies of study of hepatotoxicity. Read More

    Systems pharmacology modeling of drug-induced hyperbilirubinemia: Differentiating hepatotoxicity and inhibition of enzymes/transporters.
    Clin Pharmacol Ther 2017 Jan 11. Epub 2017 Jan 11.
    DILIsym Services Inc, Research Triangle Park, North Carolina, USA.
    Elevations in serum bilirubin during drug treatment may indicate global liver dysfunction and a high risk of liver failure. However, drugs also can increase serum bilirubin in the absence of hepatic injury by inhibiting specific enzymes/transporters. We constructed a mechanistic model of bilirubin disposition based on known functional polymorphisms in bilirubin metabolism/transport. Read More

    TAMH: A Useful In Vitro Model for Assessing Hepatotoxic Mechanisms.
    Biomed Res Int 2016 15;2016:4780872. Epub 2016 Dec 15.
    Pacific University School of Pharmacy, 222 SE 8th Avenue No. 451, Hillsboro, OR 97123, USA.
    In vitro models for hepatotoxicity can be useful tools to predict in vivo responses. In this review, we discuss the use of the transforming growth factor-α transgenic mouse hepatocyte (TAMH) cell line, which is an attractive model to study drug-induced liver injury due to its ability to retain a stable phenotype and express drug-metabolizing enzymes. Hepatotoxicity involves damage to the liver and is often associated with chemical exposure. Read More

    A monkey model of acetaminophen-induced hepatotoxicity; phenotypic similarity to human.
    J Toxicol Sci 2017 ;42(1):73-84
    Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd.
    Species-specific differences in the hepatotoxicity of acetaminophen (APAP) have been shown. To establish a monkey model of APAP-induced hepatotoxicity, which has not been previously reported, APAP at doses up to 2,000 mg/kg was administered orally to fasting male and female cynomolgus monkeys (n = 3-5/group) pretreated intravenously with or without 300 mg/kg of the glutathione biosynthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO). In all the animals, APAP at 2,000 mg/kg with BSO but not without BSO induced hepatotoxicity, which was characterized histopathologically by centrilobular necrosis and vacuolation of hepatocytes. Read More

    Transgenic Zebrafish Reporter Lines as Alternative In Vivo Organ Toxicity Models.
    Toxicol Sci 2017 Jan 9. Epub 2017 Jan 9.
    *Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, 138673 Singapore
    Organ toxicity, particularly liver toxicity, remains one of the major reasons for the termination of drug candidates in the development pipeline as well as withdrawal or restrictions of marketed drugs. A screening-amenable alternative in vivo model such as zebrafish would, therefore, find immediate application in the early prediction of unacceptable organ toxicity. To identify highly upregulated genes as biomarkers of toxic responses in the zebrafish model, a set of well-characterized reference drugs that cause drug-induced liver injury (DILI) in the clinic were applied to zebrafish larvae and adults. Read More

    Live donor liver transplantation for antitubercular drug-induced acute liver failure.
    Indian J Gastroenterol 2017 Jan 9. Epub 2017 Jan 9.
    Department of Gastrointestinal and Multiviceral Transplant Surgery, Amrita Institute of Medical Sciences and Research Centre, Ponnekkara, Kochi, 572 101, India.
    Antitubercular therapy (ATT)-induced hepatotoxicity is often over looked and active tuberculosis is considered a contraindication for liver transplantation, however it might be the only lifesaving option to certain patients of acute liver failure (ALF) due to ATT. We have assessed the outcome of live donor liver transplantation in ATT-induced ALF. A retrospective analysis of all the cases of ALF that underwent liver transplantation from 2006 to 2014 at the Amrita Institute of Medical Sciences was done. Read More

    The novel role of β-aescin in attenuating CCl4-induced hepatotoxicity in rats.
    Pharm Biol 2017 Dec;55(1):749-757
    b Sri Sai College of Pharmacy, Badhani , Pathankot , Punjab , India.
    Context: β-Aescin has anti-inflammatory, anti-oxidant and antiedematous properties.

    Objective: The present study investigated the hepatoprotective effect and underlying mechanisms of β-aescin in CCl4-induced liver damage.

    Materials And Methods: Thirty-five Wistar rats were divided into six groups: normal control, CCl4 control, silymarin (50 mg/kg, p. Read More

    Pyrazinamide-induced hepatotoxicity is alleviated by 4-PBA via inhibition of the PERK-eIF2α-ATF4-CHOP pathway.
    Toxicology 2017 Mar 4;378:65-75. Epub 2017 Jan 4.
    Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 211198, China. Electronic address:
    Pyrazinamide (PZA)-induced serious liver injury, but the exact mechanism of PZA-induces hepatotoxicity remains controversial. Endoplasmic reticulum (ER) stress-caused cell apoptosis plays a critical role in the development of drug-induced liver injury (DILI). However, the direct connection between PZA toxicity and ER stress is unknown. Read More

    Effects of 31 FDA approved small-molecule kinase inhibitors on isolated rat liver mitochondria.
    Arch Toxicol 2016 Dec 28. Epub 2016 Dec 28.
    Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR, 72079, USA.
    The FDA has approved 31 small-molecule kinase inhibitors (KIs) for human use as of November 2016, with six having black box warnings for hepatotoxicity (BBW-H) in product labeling. The precise mechanisms and risk factors for KI-induced hepatotoxicity are poorly understood. Here, the 31 KIs were tested in isolated rat liver mitochondria, an in vitro system recently proposed to be a useful tool to predict drug-induced hepatotoxicity in humans. Read More

    Adenosine 5'-monophosphate blocks acetaminophen toxicity by increasing ubiquitination-mediated ASK1 degradation.
    Oncotarget 2017 Jan;8(4):6273-6282
    Center for Molecular Metabolism, Nanjing University of Science and Technology, Nanjing, 210094, China.
    Acetaminophen (APAP) overdose is the most frequent cause of drug-induced liver failure in the world. Hepatic c-jun NH2-terminal protein kinase (JNK) activation is thought to be a consequence of oxidative stress produced during APAP metabolism. Activation of JNK signals causes hepatocellular damage with necrotic and apoptotic cell death. Read More

    Metabolomic Study on Idiosyncratic Liver Injury Induced by Different Extracts of Polygonum multiflorum in Rats Integrated with Pattern Recognition and Enriched Pathways Analysis.
    Front Pharmacol 2016 15;7:483. Epub 2016 Dec 15.
    China Military Institute of Chinese Medicine, 302 Military Hospital Beijing, China.
    Currently, numerous liver injury cases related to a famous Chinese herb- Polygonum Multiflorum (Heshouwu in Chinese) have attracted great attention in many countries. Our previous work showed that Heshouwu-induced hepatotoxicity belonged to idiosyncratic drug-induced liver injury (IDILI). Unfortunately, the components and mechanisms attributed to IDILI of Heshouwu are difficult to determine and thus remain unknown. Read More

    Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation.
    World J Gastroenterol 2016 Dec;22(45):10071-10076
    Keri E Lunsford, Adam S Bodzin, Diego C Reino, Ronald W Busuttil, The Pfleger Liver Institute, The Dumont-UCLA Liver Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA 90095, United States.
    Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, however, are the associated harmful side effects, often unrecognized by consumers. Read More

    Analysis of Immunogenetic Factors in Idiosyncratic Drug-Induced Liver Injury in the Paediatric Population.
    J Pediatr Gastroenterol Nutr 2016 Dec 22. Epub 2016 Dec 22.
    *Complejo Hospitalario Universitario de Granada. UGC Médico quirúrgica de la infancia, Cuidados Intensivos Pediátricos. Universidad de Granada. CIBERehd. Granada. España †Complejo Hospitalario Universitario de Granada. UGC Médico quirúrgica de la infancia Granada. España ‡Laboratorios Investigación. ibs. Complejo Hospitalario Universitario de Granada. España §Hospital Universitario La Paz. Madrid. España ||Complejo Hospitalario de Jaén. Jaén España ¶Complejo Hospitalario Universitario de Granada. Granada. Universidad de Granada. CIBERehd. Granada. España.
    Objective: Idiosyncratic drug-induced liver injury (DILI) is a multifactorial complex disease, in which the toxic potential of the drug, together with genetic and acquired factors and deficiencies in adaptive processes which limit the extent of damage, can determine susceptibility and make individuals unique in their development of hepatotoxicity. The aim of this study is to analyse the genetic factors (HLA, cytokine polymorphisms and KIR genotype) of children who experience an episode of drug-induced liver injury.

    Subjects And Method: Prospective multicentre case control study. Read More

    Changes in IL-2 and IL-10 during Chronic Administration of Isoniazid, Nevirapine, and Paracetamol in Rats.
    Adv Pharmacol Sci 2016 20;2016:3094783. Epub 2016 Nov 20.
    Department of Pharmacology, University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa.
    The aim of this study was to illustrate the initial subclinical drug-induced liver injury and the associated adaptive immune response by monitoring for the changes in plasma IL-2, IL-10, and some cytochrome P450 activity during chronic administration of nevirapine (NVP), isoniazid (INH), and paracetamol (PAR) in rats without clinical hepatotoxicity. Male Sprague-Dawley (SD) rats were divided into four groups (saline (S), NVP, INH, and PAR) of 25 animals each. The drugs were administered daily for 42 days at therapeutic doses (NVP 200 mg/kg, PAR 500 mg/kg, and INH 20 mg/kg) to the respective groups by oral gavage and five rats per group were sacrificed weekly. Read More

    Lycopene inhibits reactive oxygen species production in SK-Hep-1 cells and attenuates acetaminophen-induced liver injury in C57BL/6 mice.
    Chem Biol Interact 2017 Feb 15;263:7-17. Epub 2016 Dec 15.
    Postgraduated Program in Biological Sciences of the Research Center for Biological Sciences - NUPEB, Federal University of Ouro Preto (UFOP), Ouro Preto, MG, 35.400-000, Brazil; Department of Biological Sciences, Universidade Federal de Ouro Preto (UFOP), Ouro Preto, Brazil. Electronic address:
    Our aim was to investigate the antioxidant potential of lycopene in different experimental liver models: in vitro, to evaluate the influence of lycopene on reactive oxygen species (ROS) production mediated by the PKC pathway and in vivo, to evaluate the protective effects of lycopene in an experimental model of hepatotoxicity. The in vitro study assessed the lycopene antioxidant potential by the quantification of ROS production in SK-Hep-1 cells unstimulated or stimulated by an activator of the PKC pathway. The role of NADPH oxidase was evaluated by measuring its inhibition potential using an inhibitor of this enzyme. Read More

    Competing Mechanistic Hypotheses of Acetaminophen-Induced Hepatotoxicity Challenged by Virtual Experiments.
    PLoS Comput Biol 2016 Dec 16;12(12):e1005253. Epub 2016 Dec 16.
    Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States of America.
    Acetaminophen-induced liver injury in mice is a model for drug-induced liver injury in humans. A precondition for improved strategies to disrupt and/or reverse the damage is a credible explanatory mechanism for how toxicity phenomena emerge and converge to cause hepatic necrosis. The Target Phenomenon in mice is that necrosis begins adjacent to the lobule's central vein (CV) and progresses outward. Read More

    [Current status of Chinese herbal preparations included in LiverTox database].
    Zhonghua Gan Zang Bing Za Zhi 2016 Nov;24(11):817-823
    Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
    Objective: To investigate the contents and features of drug-induced liver injury (DILI) database called LiverTox, as well as 37 herbal preparations included in this database. Methods: Firstly, the source and contents of LiverTox were briefly introduced, including the clinical features, types, severity, and causality assessment scale of DILI. Secondly, detailed information of 37 herbal preparations included in the class of "Herbals and Dietary Supplements" were extracted, including drug name, origin, efficacy, constituents, type of liver injury, and manifestations, to perform a preliminary statistical analysis. Read More

    A longitudinal assessment of miR-122 and GLDH as biomarkers of drug-induced liver injury in the rat.
    Biomarkers 2016 Dec 15:1-9. Epub 2016 Dec 15.
    g Department of Physiology and Pharmacology, Science for Life Laboratory , Karolinska Institutet , Stockholm , Sweden.
    Context: There is an ongoing search for specific and translational biomarkers of drug-induced liver injury (DILI). MicroRNA-122 (miR-122) has previously shown potential as a sensitive, specific, and translational biomarker of DILI in both rodent, and human studies.

    Objective: To build on previous work within the field, we examined biomarker kinetics in a rat model of acetaminophen (APAP)-induced liver injury to confirm the sensitivity, and specificity of miR-122 and glutamate dehydrogenase (GLDH). Read More

    Drug-induced liver injury: a cohort study on patients referred to the Danish transplant center over a five year period.
    Scand J Gastroenterol 2017 Apr 15;52(4):450-454. Epub 2016 Dec 15.
    a Department of Hepatology , Rigshospitalet, University Hospital of Copenhagen , Copenhagen , Denmark.
    Objective: The idiosyncratic subtype of drug-induced liver injury (DILI) is a rare reaction to medical treatment that in severe cases can lead to acute liver failure and death. The aim of this study was to describe the presentation and outcome of DILI and to identify potential predictive factors of poor outcome.

    Materials And Methods: We identified all patients diagnosed with DILI at the Department of Hepatology, Rigshospitalet, from March 2007 to November 2012. Read More

    The histopathological evaluation of drug-induced liver injury.
    Histopathology 2017 Jan;70(1):81-93
    Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
    Drug-induced liver injury (DILI) presents unique challenges to the pathologist. It is not only an uncommon reason for liver biopsy, but the pathology of DILI is spread across the entire spectrum of hepatic injury patterns. It is important for the pathologist to suspect DILI when the histological changes are unusual or out of synchronicity with the patient's history. Read More

    Drug-induced liver injury.
    Clin Med (Lond) 2016 Dec;16(Suppl 6):s104-s109
    Department of Medicine, Brighton and Sussex Medical School, and Department of Gastroenterology and Hepatology, Brighton and University Hospital, Brighton, UK.
    Drug-induced liver injury (DILI) remains the most common cause of acute liver failure (ALF) in the western world. Excluding paracetamol overdose, nearly all DILI encountered in the clinical setting is idiosyncratic in nature because affected individuals represent only a small proportion of those treated with such drugs. In many cases, the mechanism for idiosyncrasy is immune-mediation and is often identified by genetic risk determined by human leukocyte antigen variants. Read More

    Medical plant extracts and natural compounds with a hepatoprotective effect against damage caused by antitubercular drugs: A review.
    Asian Pac J Trop Med 2016 Dec 9;9(12):1141-1149. Epub 2016 Nov 9.
    Unidad de Investigación Médica en Farmacología, UMAE Hospital de Especialidades, Centro Médico Nacional-Siglo XXI, Instituto Mexicano del Seguro Social, México City, Mexico.
    Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. Read More

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