33,189 results match your criteria Drug-Induced Hepatotoxicity


Biomarkers of Drug-Induced Liver Toxicity.

Authors:
Manuela G Neuman

Ther Drug Monit 2019 Apr;41(2):227-234

In Vitro Drug Safety and Biotechnology, Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.

Drug-induced liver injury (DILI) is a comprehensive phenomenon. The injury to the liver may occur as an unexpected and undesired reaction to a therapeutic dose of a drug (idiosyncratic reaction) or as an expected therapeutic effect of the direct (intrinsic) toxicity of a drug taken in a large enough dose to cause liver injury. The direct toxicity (type A) reactions represent an extension of the drug's therapeutic effect; they occur relatively frequently and are typically dose-related and frequency-of-exposure-related. Read More

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http://Insights.ovid.com/crossref?an=00007691-201904000-0001
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http://dx.doi.org/10.1097/FTD.0000000000000610DOI Listing
April 2019
3 Reads

Incidence, clinical features, and risk factors of fluoroquinolone-induced acute liver injury: a case-control study.

Ther Clin Risk Manag 2019 8;15:389-395. Epub 2019 Mar 8.

Department of Pharmaceutical Care, General Hospital of People's Liberation Army, Beijing 100853, China,

Background: Fluoroquinolone-related hepatotoxicity is rare but serious and is attracting increasing attention. We explored the incidence, clinical features and risk factors of acute liver injury associated with fluoroquinolone use.

Materials And Methods: Based on the Adverse Drug Events Active Surveillance and Assessment System that we developed, we carried out a case-control study by enrolling patients who were hospitalized and received fluoroquinolones to treat or prevent infections at the Chinese People's Liberation Army General Hospital from Jan 2016 to Dec 2017. Read More

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http://dx.doi.org/10.2147/TCRM.S195802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413755PMC

Determination of fasiglifam-induced liver toxicity: Insights from the data monitoring committee of the fasiglifam clinical trials program.

Clin Trials 2019 Mar 18:1740774519836766. Epub 2019 Mar 18.

1 Duke Clinical Research Institute, Durham, NC, USA.

Background: Different approaches to safety event collection influence the determination of liver toxicity within drug development programs. Herein, a description of how fasiglifam-induced liver injury was detected is provided.

Methods: This eight-trial drug development program was intended to evaluate fasiglifam (25 mg, 50 mg) against placebo or active comparators (glimepiride, sitagliptin) in approximately 11,000 suboptimally controlled patients with type 2 diabetes (terminated Dec 2013 due to liver toxicity). Read More

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http://dx.doi.org/10.1177/1740774519836766DOI Listing

Hepatoprotective properties of Curcuma longa L. extract in bleomycin-induced chronic hepatotoxicity.

Drug Discov Ther 2019 ;13(1):9-16

Department of Physiology, Pathophysiology and Pharmacology, Faculty of Medicine, Trakia University.

Curcuma longa L. (CLL) extract has previously been reported to alleviate liver damage. The current study examined the antioxidant activity of CLL by which the extract protects the liver against bleomycin (BLM)-induced hepatotoxicity in mice. Read More

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http://dx.doi.org/10.5582/ddt.2018.01081DOI Listing
January 2019

Activation of PERK-eIF2α-ATF4 pathway contributes to diabetic hepatotoxicity: Attenuation of ER stress by Morin.

Cell Signal 2019 Mar 12. Epub 2019 Mar 12.

Herbal Research Laboratory, Food, Drug & Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhavan 31, M.G Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Toxicology Research, Lucknow, India. Electronic address:

Hyperglycemia associated ER stress has been found as a critical contributor in the pathogenesis of type 2 diabetes mellitus. However, reports regarding molecular mechanisms involved are limited. This study was aimed to identify the role of ER stress in regulating hepatic glucose metabolism and its link with oxidative stress. Read More

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http://dx.doi.org/10.1016/j.cellsig.2019.03.008DOI Listing

Pro-inflammatory cytokines enhance dilatation of bile canaliculi caused by cholestatic antibiotics.

Toxicol In Vitro 2019 Mar 12. Epub 2019 Mar 12.

Univ Rennes, Inserm, Inra, Institut NUMECAN (Nutrition Metabolisms and Cancer), UMR_S 1241, 35000 Rennes, France. Electronic address:

Many drugs can induce liver injury, characterized by hepatocellular, cholestatic or mixed hepatocellular-cholestatic lesions. While an inflammatory stress is known to aggravate hepatocellular injury caused by some drugs much less evidence exists for cholestatic features. In this study, the influence of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α), either individually or combined, on cytotoxic and cholestatic properties of antibiotics was evaluated using differentiated HepaRG cells. Read More

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http://dx.doi.org/10.1016/j.tiv.2019.03.015DOI Listing

Liver Injury Induced by Carbon Tetrachloride in Mice Is Prevented by the Antioxidant Capacity of Anji White Tea Polyphenols.

Antioxidants (Basel) 2019 Mar 14;8(3). Epub 2019 Mar 14.

Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing 400067, China.

Anji white tea is a unique variety of green tea that is rich in polyphenols. In this study, the effect of Anji white tea polyphenols (AJWTP) on the prevention of carbon tetrachloride (CCl₄)-induced liver injury through its antioxidant properties was studied. Biochemical and molecular biology methods were used to analyze the serum and liver tissue of mice. Read More

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https://www.mdpi.com/2076-3921/8/3/64
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http://dx.doi.org/10.3390/antiox8030064DOI Listing
March 2019
1 Read

Statins and nonalcoholic fatty liver disease in the era of precision medicine: More friends than foes.

Atherosclerosis 2019 Mar 3;284:66-74. Epub 2019 Mar 3.

Operating Unit of Internal and Metabolic Medicine, Azienda Ospedaliero-Universitaria of Modena, Civil Hospital of Baggiovara, Via Giardini 1355, 41126, Modena, Italy.

Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of alcohol-like hepatic histological changes, which occur in the absence of any competing causes of chronic liver disease, notably including significant alcohol consumption. A close and bi-directional relationship links NAFLD with the metabolic syndrome (MetS), and concurrent MetS will hasten the progression to more severe forms of NAFLD, including cirrhosis and hepatocellular carcinoma (HCC). Patients with NAFLD will typically exhibit atherogenic dyslipidemia and increased cardiovascular risk (CVR). Read More

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http://dx.doi.org/10.1016/j.atherosclerosis.2019.02.028DOI Listing

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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May 2018
1 Read

Protective effect of surface-modified berberine nanoparticles against LPS-induced neurodegenerative changes: a preclinical study.

Drug Deliv Transl Res 2019 Mar 13. Epub 2019 Mar 13.

Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.

Berberine (BBR) exerts documented protection against neurodegenerative disorders. However, data on the effect of nano-encapsulation on the neuroprotective effect of BBR are lacking. We investigated the effect of BBR loading into chitosan (CS) nanoparticles (NPs) and their surface modification with Tween 80 (T80), polyethylene glycol 4000 (PEG), and miltefosine (MFS) against lipopolysaccharide (LPS)-induced neurodegenerative changes in addition to hepatotoxicity in rats. Read More

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http://dx.doi.org/10.1007/s13346-019-00626-1DOI Listing

Tools for causality assessment in drug-induced liver disease.

Curr Opin Gastroenterol 2019 Mar 6. Epub 2019 Mar 6.

Department of Medicine, Medical University South Carolina, Charleston, USA.

Purpose Of Review: There are three liver-specific causality assessment tools currently available to guide clinical diagnosis of Drug-Induced Liver Injury (DILI): Roussel-Uclaf Causality Assessment Method (RUCAM), Digestive-Disease-Week Japan 2004 scale (DDW-J), and Clinical Diagnostic Scale (CDS). The purpose of this review is to assess these tools and discuss how to improve the causality assessment process as a whole.

Recent Findings: Existing DILI-specific causality assessment tools are surprisingly similar and exhibit only minor differences in point allocation. Read More

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http://dx.doi.org/10.1097/MOG.0000000000000526DOI Listing

Ursodeoxycholic acid attenuates hepatotoxicity of multidrug treatment of mycobacterial infections: A prospective pilot study.

Int J Mycobacteriol 2019 Jan-Mar;8(1):89-92

Outpatient Department, SRH Policlinic, Gera, Germany.

Background: Tuberculosis (TB) remains a global health problem. The application of rifampicin-based regimens for antimycobacterial therapy is hampered by its marked hepatotoxicity which results in poor adherence and may contribute to prolonged therapy or treatment failure. The purpose of this prospective investigation was to evaluate the hepatoprotective effectiveness of oral ursodeoxycholic acid (UDCA) (250-500 mg TID) administered to TB- or non-TB mycobacterial (NTM)-infected patients with drug-induced hepatotoxicity and ongoing therapy. Read More

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http://dx.doi.org/10.4103/ijmy.ijmy_159_18DOI Listing

Hepatotoxicity induced by Isoniazid/Lipopolysaccharide through ERS-, autophagy- and apoptosis pathway in zebrafish.

Antimicrob Agents Chemother 2019 Mar 11. Epub 2019 Mar 11.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, Key laboratory for Biosensor of Shandong Province, 28789 Jingshidong Road, Licheng District, Jinan, Shandong Province, PR China.

Isoniazid (INH) is a first-line antituberculosis drug. The incidence of adverse reactions accompanied by inflammation in the liver during drug administration to tuberculosis patients is high and severely affects clinical treatment. To better understanding the mechanism of hepatotoxicity induced by INH under the inflammatory state, we compared the differences in hepatotoxicity from INH between normal and inflammatory zebrafish to elucidate the hepatotoxic mechanism using different endpoints such as mortality, malformation, inflammatory effects, liver morphology, histological changes, transaminase analysis and certain genes expression. Read More

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http://dx.doi.org/10.1128/AAC.01639-18DOI Listing
March 2019
2 Reads

Total flavonoids, extracted from Polygonum knotweed L, exert beneficial hepatoprotection against liver injury.

J Cell Biochem 2019 Mar 10. Epub 2019 Mar 10.

Department of Pharmacy, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

Hepatic function is of great concern in metabolic and immunological homeostasis. Traditionally, medical management to liver damage may benefit from phytomedicine, such as Chinese herbs. In southern China, Polygonum perfoliatum L can contribute to alleviating pathological symptoms of liver disease, such as hepatitis. Read More

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http://doi.wiley.com/10.1002/jcb.28535
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http://dx.doi.org/10.1002/jcb.28535DOI Listing
March 2019
1 Read

The Power of Resolution: Contextualized Understanding of Biological Responses to Liver Injury Chemicals using High-throughput Transcriptomics and Benchmark Concentration Modeling.

Toxicol Sci 2019 Mar 8. Epub 2019 Mar 8.

Division of National Toxicology Program, National Institutes of Environmental Health Sciences of National Institutes of Health, Durham, NC, USA.

Prediction of human response to chemical exposures is a major challenge in both pharmaceutical and toxicological research. Transcriptomics has been a powerful tool to explore chemical-biological interactions, however, limited throughput, high-costs and complexity of transcriptomic interpretations have yielded numerous studies lacking sufficient experimental context for predictive application. To address these challenges, we have utilized a novel high-throughput transcriptomics (HTT) platform, TempO-Seq, to apply the interpretive power of concentration-response modeling with exposures to 24 reference compounds in both differentiated and non-differentiated human HepaRG cell cultures. Read More

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http://dx.doi.org/10.1093/toxsci/kfz065DOI Listing

Oral administration of carvacrol/β-cyclodextrin complex protects against 6-hydroxydopamine-induced dopaminergic denervation.

Neurochem Int 2019 Mar 5;126:27-35. Epub 2019 Mar 5.

Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Carvacrol (CARV) presents valuable biological properties such as anti-inflammatory and antioxidant activities. However, pharmacological uses of CARV are largely limited due to disadvantages related to solubility, bioavailability, preparation and storage processes. The complexation of monoterpenes with β-cyclodextrin (β-CD) increases their stability, solubility and oral bioavailability. Read More

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http://dx.doi.org/10.1016/j.neuint.2019.02.021DOI Listing
March 2019
2 Reads
3.092 Impact Factor

Stem-cell derived hepatocyte-like cells for the assessment of drug-induced liver injury.

Differentiation 2019 Feb 19;106:15-22. Epub 2019 Feb 19.

Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia, 46026, Spain.

Drug-induced liver injury is a major cause of drug discovery failure in clinical trials and a leading cause of liver disease. Current preclinical drug testing does not predict hepatotoxicity which highlights the importance of developing highly predictive cell-based models. The use of stem cell technology and differentiation into hepatocyte-like cells (HLCs) could provide a stable source of hepatocytes for multiple applications, including drug screening. Read More

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http://dx.doi.org/10.1016/j.diff.2019.02.004DOI Listing
February 2019

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
4 Reads
3.126 Impact Factor

NUDT15 Polymorphism identified in an Azathioprine Hypersensitivity Syndrome Presenting as Erythema Nodosum and Hepatotoxicity.

Br J Dermatol 2019 Mar 6. Epub 2019 Mar 6.

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Linkou, Keelung, Taiwan.

Azathioprine (AZA) is a thiopurine-derived immunosuppressant commonly used in autoimmune and immunobullous dermatoses. AZA-hypersensitivity syndrome is a rare, but potentially fatal, immune-mediated reaction occurring within four weeks of administration. The polymorphism of TPMT and NUDT15 gene has been shown to increase the risk of AZA-induced leukopenia . Read More

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http://dx.doi.org/10.1111/bjd.17859DOI Listing
March 2019
1 Read

Novel risk assessment of reactive metabolites from discovery to clinical stage.

J Toxicol Sci 2019 ;44(3):201-211

Drug Metabolism & Pharmacokinetics Research Laboratories, Central Pharmaceutical Research Institute.

This study was aimed to predict drug-induced liver injury caused by reactive metabolites. Reactive metabolites covalently bind to proteins and could result in severe outcomes in patients. However, the relation between the extent of covalent binding and clinical hepatotoxicity is still unclear. Read More

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http://dx.doi.org/10.2131/jts.44.201DOI Listing
January 2019

Thymoquinone attenuates rheumatoid arthritis by downregulating TLR2, TLR4, TNF-α, IL-1, and NFκB expression levels.

Biomed Pharmacother 2019 Mar 9;111:958-963. Epub 2019 Jan 9.

Department of Biological Sciences, Forman Christian College University, Lahore, Pakistan.

Background: Thymoquinone (TQ), the most important active principle of Nigella sativa is known to have anti-inflammatory, analgesic, antimicrobial and antioxidant properties.

Aim: The present study was designed to see the anti-arthritic effect of TQ in rat model of arthritis.

Methods: In the current research, anti-arthritic effect of TQ was determined in Freund's Complete Adjuvant (FCA)-induced arthritic rats by measuring TLRs expression levels. Read More

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http://dx.doi.org/10.1016/j.biopha.2019.01.006DOI Listing
March 2019
1 Read
2.023 Impact Factor

Hepatic steatosis and patients with inflammatory bowel disease: when transient elastography makes the difference.

Eur J Gastroenterol Hepatol 2019 Mar 6. Epub 2019 Mar 6.

Department of Gastroenterology, Hospital da Senhora da Oliveira.

Background: Recent studies suggest an increased prevalence of hepatic steatosis (HS) in patients with inflammatory bowel disease (IBD). Features such as chronic inflammation, previous surgeries, drug-induced hepatotoxicity, malnutrition, and intestinal dysbiosis seem to be involved in its pathogenesis.

Aims: The aim of this study was to assess the frequency of HS in patients with IBD quantified by controlled attenuation parameter (CAP) and by clinical-analytical scores: Hepatic Steatosis Index (HSI) and Fatty Liver Index (FLI). Read More

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http://dx.doi.org/10.1097/MEG.0000000000001319DOI Listing
March 2019
1 Read

Histological study of the protective role of ginger on piroxicam-induced liver toxicity in mice.

J Chin Med Assoc 2019 Jan;82(1):11-18

Background: Piroxicam is a non-steroidal anti-inflammatory drug widely used in rheumatic diseases. It has analgesic and antipyretic activity, and is one of the drugs being introduced in clinical practice. Piroxicam-hepatotoxicity has been reported as one of its principal side effects. Read More

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http://Insights.ovid.com/crossref?an=02118582-201901000-0000
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http://dx.doi.org/10.1016/j.jcma.2018.06.006DOI Listing
January 2019
1 Read

Thymoquinone, an Active Constituent of Black Seed Attenuates CCl4 Induced Liver Injury in Mice via Modulation of Antioxidant Enzymes, PTEN, P53 and VEGF Protein.

Open Access Maced J Med Sci 2019 Feb 4;7(3):311-317. Epub 2019 Feb 4.

Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah, Saudi Arabia.

Aim: The present study was undertaken to evaluate the possible protective role of thymoquinone on CCl4-induced hepatotoxicity.

Methods: The activities of liver function enzymes and antioxidant enzymes were measured. Haematoxylin-Eosin staining was performed to analyze the live tissue alterations. Read More

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http://dx.doi.org/10.3889/oamjms.2019.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390143PMC
February 2019

Protective effect of 7,3',4'-flavon-3-ol (fisetin) on acetaminophen-induced hepatotoxicity in vitro and in vivo.

Phytomedicine 2019 Feb 19;58:152865. Epub 2019 Feb 19.

Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address:

Background: Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in clinic. Fisetin (FST) is a phenolic compound that has been isolated from many natural products.

Purpose: Our aim is to study the protection effect and mechanisms of FST on APAP-induced hepatotoxicity in endogenous metabolism and metabolomics in vitro and in vivo. Read More

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http://dx.doi.org/10.1016/j.phymed.2019.152865DOI Listing
February 2019

Ultralow doses of dextromethorphan protect mice from endotoxin-induced sepsis-like hepatotoxicity.

Chem Biol Interact 2019 Feb 26;303:50-56. Epub 2019 Feb 26.

Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.

Dextromethorphan, a wildly used over-the-counter antitussive drug, is reported to have anti-inflammatory effects. Previously, we and others have demonstrated that dextromethorphan at micromolar doses displays potent hepatoprotective effects and enhances mice survival in a sepsis model. Moreover, we also observed potent anti-inflammatory and neuroprotective effects of subpicomolar concentrations of dextromethorphan in rodent primary neuron-glial cultures. Read More

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http://dx.doi.org/10.1016/j.cbi.2019.02.025DOI Listing
February 2019
2 Reads

Acute liver injury leading to death in the setting of brentuximab vedotin monotherapy.

Leuk Lymphoma 2019 Mar 1:1-4. Epub 2019 Mar 1.

a Oncology Department , Epworth Health Care, Epworth Eastern Hospital , Richmond , Australia.

A 67-year-old man with an 11-year history of composite lymphoma was admitted with fevers in the context of neutropenia and acute liver injury, 4 months after the commencement of single-agent brentuximab vedotin. Fevers resolved with intravenous antibiotics, however, his liver function tests remained abnormal and he continued to be deeply jaundiced over the course of his 3-week illness. A liver screen failed to indicate a cause for his liver function test abnormalities and two separate liver biopsies were suggestive of drug-induced liver injury. Read More

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https://www.tandfonline.com/doi/full/10.1080/10428194.2019.1
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http://dx.doi.org/10.1080/10428194.2019.1579321DOI Listing
March 2019
2 Reads

Double deletion of PINK1 and Parkin impairs hepatic mitophagy and exacerbates acetaminophen-induced liver injury in mice.

Redox Biol 2019 Feb 20;22:101148. Epub 2019 Feb 20.

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA. Electronic address:

Mitochondria damage plays a critical role in acetaminophen (APAP)-induced necrosis and liver injury. Cells can adapt and protect themselves by removing damaged mitochondria via mitophagy. PINK1-Parkin pathway is one of the major pathways that regulate mitophagy but its role in APAP-induced liver injury is still elusive. Read More

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http://dx.doi.org/10.1016/j.redox.2019.101148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395945PMC
February 2019
2 Reads

The A/A Genotype of XPO1 rs4430924 Is Associated With Higher Risk of Antituberculosis Drug-Induced Hepatotoxicity in Chinese Patients.

J Clin Pharmacol 2019 Feb 28. Epub 2019 Feb 28.

Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.

Antituberculosis (anti-TB) drug-induced hepatotoxicity may be related to the excessive reactive oxygen species induced by hepatotoxic metabolites. Antioxidant activity involves the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. The BTB domain and CNC homologue 1 (Bach1) may compete with Nrf2 for binding to transcriptional enhancers. Read More

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http://dx.doi.org/10.1002/jcph.1398DOI Listing
February 2019
1 Read

Peroxynitrite Activatable NIR-II Fluorescent Molecular Probe for Drug-Induced Hepatotoxicity Monitoring.

Anal Chem 2019 Mar 12. Epub 2019 Mar 12.

Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, State Key Laboratory of Molecular Engineering of Polymers and iChem , Fudan University , Shanghai 200433 , P. R. China.

Drug-induced hepatotoxicity represents an important challenge for safety in drug development. The production of peroxynitrite (ONOO) is proposed as an early sign in the progression of drug-induced hepatotoxicity. Currently, reported ONOO probes mainly emit in the visible range or the first NIR window, which have limited in vivo biosensing application due to the autofluorescence and photon scattering. Read More

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http://pubs.acs.org/doi/10.1021/acs.analchem.9b00317
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http://dx.doi.org/10.1021/acs.analchem.9b00317DOI Listing
March 2019
11 Reads

Biomarkers of drug-induced liver toxicity.

Authors:
Manuela G Neuman

Ther Drug Monit 2019 Feb 19. Epub 2019 Feb 19.

In Vitro Drug Safety and Biotechnology, Department of Pharmacology and Toxicology, University of Toronto.

Drug-induced liver injury (DILI) is a comprehensive phenomenon. The injury to the liver may occur as an unexpected and undesired reaction to a therapeutic dose of a drug (idiosyncratic reaction), or as an expected therapeutic effect of the direct (intrinsic) toxicity of a drug taken in a large enough dose to cause liver injury.The direct toxicity (Type A) reactions represent an extension of the drug's therapeutic effect; they occur relatively frequently and are typically dose-related and frequency-of-exposure-related. Read More

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http://dx.doi.org/10.1097/FTD.0000000000000610DOI Listing
February 2019

Activated TNF-α/RIPK3 signaling is involved in prolonged high fat diet-stimulated hepatic inflammation and lipid accumulation: inhibition by dietary fisetin intervention.

Food Funct 2019 Feb 22. Epub 2019 Feb 22.

Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China. and Research Center of Brain Intellectual Promotion and Development for Children Aged 0-6 Years, Chongqing University of Education, Chongqing 400067, PR China.

Increasing evidence indicates that high-fat diet (HFD) is a predisposing factor for metabolic syndrome-associated systemic inflammation and nonalcoholic fatty liver disease (NAFLD). Tumor necrosis factor-α/receptor-interacting protein kinase 3 (TNF-α/RIPK3) axis has recently become regarded as an important regulator and contributor in many inflammation-related diseases. Fisetin (Fn) is a bioactive flavonoid polyphenol with anti-inflammatory and anti-tumor activity. Read More

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http://dx.doi.org/10.1039/c8fo01615aDOI Listing
February 2019
2.791 Impact Factor

Inhibition of mitochondrial complex I by rotenone protects against acetaminophen-induced liver injury.

Am J Transl Res 2019 15;11(1):188-198. Epub 2019 Jan 15.

Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University 72 Guangzhou Road, Nanjing 210008, P. R. China.

Acetaminophen (APAP) is widely used as an antipyretic analgesic in clinic. However, overdose-related severe liver injury is a major concern of this drug. Recently, accumulating evidence indicated an important role of mitochondrial abnormality in the pathogenesis of APAP hepatoxicity. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357306PMC
January 2019
3.226 Impact Factor

Phase I study of PF-04895162, a Kv7 channel inhibitor, reveals unexpected hepatotoxicity in healthy subjects, but not rats or monkeys: clinical evidence of disrupted bile acid homeostasis.

Pharmacol Res Perspect 2019 02;7(1):e00467

Clinical Pharmacology, Early Clinical Development, Pfizer Inc., Cambridge, UK.

During a randomized Phase 1 clinical trial the drug candidate, PF-04895162 (ICA-105665), caused transaminase elevations (≥grade 1) in six of eight healthy subjects treated at 300 mg twice daily for 2-weeks (NCT01691274). This was unexpected since studies in rats (<6 months) and cynomolgus monkeys (<9 months) treated up to 100 mg/kg/day did not identify the liver as a target organ. Mechanistic studies showed PF-04895162 had low cytotoxic potential in human hepatocytes, but inhibited liver mitochondrial function and bile salt export protein (BSEP) transport. Read More

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http://dx.doi.org/10.1002/prp2.467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370995PMC
February 2019
1 Read

Association of PXR and CAR Polymorphisms and Antituberculosis Drug-Induced Hepatotoxicity.

Sci Rep 2019 Feb 18;9(1):2217. Epub 2019 Feb 18.

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

A combination therapy of multiple drugs including isoniazid, rifampicin, ethambutol and pyrazinamide has been proven to be an effective option for the vast majority of tuberculosis (TB) patients. However, various adverse drug reactions (ADRs) limit its merit, with anti-TB drug-induced hepatotoxicity (ATDH) being a common and sometimes severe ADR. This study aimed to investigate the association between polymorphisms in two nuclear receptor genes, pregnane X receptor (PXR) and constitutive androstane receptor (CAR), and the risk of ATDH in a Chinese population. Read More

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http://dx.doi.org/10.1038/s41598-018-38452-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379441PMC
February 2019
1 Read

Hepatoprotective and antioxidant effects of Hedera helix extract on acetaminophen induced oxidative stress and hepatotoxicity in mice.

Biotech Histochem 2019 Feb 19:1-7. Epub 2019 Feb 19.

e Center for Research and Training in Skin Diseases and Leprosy , Tehran University of Medical Sciences , Tehran , Iran.

Exposure to high doses of acetaminophen is the most common cause of drug induced liver injury. We investigated the protective effects of Hedera helix extract against acetaminophen induced oxidative stress and hepatotoxicity using a mouse model. We used two control groups: group A was given 0. Read More

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http://dx.doi.org/10.1080/10520295.2019.1566569DOI Listing
February 2019
2 Reads

[Chemotherapy-induced liver injury in children].

An Pediatr (Barc) 2019 Feb 15. Epub 2019 Feb 15.

UGC médico quirúrgica de la infancia, UCIP, Hospital Materno infantil Virgen de las Nieves, Universidad de Granada Ciber-EHD, Granada, España. Electronic address:

Introduction: Drug-induced liver injury due to chemotherapy is an important cause of morbidity in cancer patients, although its clinical manifestations are poorly understood.

Objective: The objective of the present study was to determine the characteristics (forms of presentation, severity, and type of injury) of hepatotoxicity due to chemotherapy in children treated for cancer.

Patients And Method: A total of 22 oncological patients were included in the study, after ruling out other causes of increased transaminases (infectious, metabolic, autoimmune, or hereditary), according to the CIOMS causality scale, it is concluded that it was a possible, probable or definite episode of hepatic injury by drugs. Read More

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http://dx.doi.org/10.1016/j.anpedi.2019.01.003DOI Listing
February 2019
3 Reads

Possible association of HMOX1 and NQO1 polymorphisms with anti-tuberculosis drug-induced liver injury: A matched case-control study.

J Clin Pharm Ther 2019 Feb 18. Epub 2019 Feb 18.

Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.

What Is Known And Objective: Reactive metabolites from anti-tuberculosis (anti-TB) drugs can result in abnormal accumulation of reactive oxygen species (ROS), which plays an important role in anti-TB drug-induced liver injury (ATLI). Liver cells could keep the production of ROS in balance by antioxidant activities. The heme oxygenase 1, encoded by the HMOX1 gene and NADH:quinone oxidoreductase 1, encoded by the NQO1 gene are crucial mediators of cellular defense against ROS. Read More

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http://dx.doi.org/10.1111/jcpt.12818DOI Listing
February 2019

Aloe emodin induces hepatotoxicity by activating NF-κB inflammatory pathway and P53 apoptosis pathway in zebrafish.

Toxicol Lett 2019 May 13;306:66-79. Epub 2019 Feb 13.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, 611137, China. Electronic address:

The aim of this study was to investigate the hepatotoxic effect and its underlying mechanism of aloe emodin (AE). AE was docked with the targets of NF-κB inflammatory pathway and P53 apoptosis pathway respectively by using molecular docking technique. To verify the results of molecular docking and further investigate the hepatotoxicity mechanism of AE, the zebrafish Tg (fabp10: EGFP) was used as an animal model in vivo. Read More

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http://dx.doi.org/10.1016/j.toxlet.2019.02.007DOI Listing
May 2019
3 Reads

Hepatoprotective effects of phosphatidylserine liposomes on carbon tetrachloride-induced hepatotoxicity in rats.

J Cell Biochem 2019 Feb 15. Epub 2019 Feb 15.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

It has been proposed carbon tetrachloride (CCl ) intoxication due to the production of free radicals and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) overload results hepatotoxicity. Phosphatidylserine (PS) has shown antioxidant activity in numerous studies. Therefore, this study was aimed to investigate the effects of PS liposomes treatment against the CCl -induced hepatotoxicity in a rat model. Read More

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http://dx.doi.org/10.1002/jcb.28464DOI Listing
February 2019
2 Reads

Idiosyncratic drug-induced acute liver failure: A challenging and distressing scenario

Curr Drug Saf 2019 02 14. Epub 2019 Feb 14.

University of Rosario School of Medicine, Rosario, Argentina.

Idiosyncratic drug induced liver injury (DILI) is a rare adverse event to drugs that occasionally leads to severe liver damage, being one of the leading causes of acute liver failure (ALF) in developed countries. DILI is largely a diagnosis of exclusion. Thus, careful history of drug taking and ruling out other competing etiologies is mandatory given that DILI can present with an extremely variable phenotype. Read More

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http://dx.doi.org/10.2174/1574886314666190215115434DOI Listing
February 2019
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The DILI-sim Initiative: Insights into Hepatotoxicity Mechanisms and Biomarker Interpretation.

Authors:
Paul Watkins

Clin Transl Sci 2019 Feb 14. Epub 2019 Feb 14.

The University of North Carolina at Chapel Hill, Institute for Drug Safety Sciences, 6 Davis Drive, PO Box 12137, North Carolina, United States.

The DILI-sim Initiative is a public-private partnership involving scientists from industry, academia and the FDA. The Initiative uses Quantitative Systems Toxicology (QST) to build and refine a model (DILIsym ) capable of understanding and predicting liver safety liabilities in new drug candidates and to optimize interpretation of liver safety biomarkers used in clinical studies. Insights gained to date include the observation that most dose-dependent hepatoxicity can be accounted for by combinations of just three mechanisms (oxidative stress, interference with mitochondrial respiration, and alterations in bile acid homeostasis) and the importance of non-competitive inhibition of bile acid transporters. Read More

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http://dx.doi.org/10.1111/cts.12629DOI Listing
February 2019
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A prospective study of the incidence of drug-induced liver injury by the modern volatile anaesthetics sevoflurane and desflurane.

Aliment Pharmacol Ther 2019 Apr 13;49(7):940-951. Epub 2019 Feb 13.

Melbourne Medical School, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia.

Background: Volatile anaesthetics are known to cause drug-induced liver injury, a hepatotoxic reaction characterised by antibodies to trifluoroacetylated lipid and protein adducts and cytochrome p450 2E1. The incidence of volatile anaesthetic drug-induced liver injury from older agents has been described, but modern agents have not been prospectively studied.

Aim: To determine prospectively the incidence of volatile anaesthetic drug-induced liver injury from sevoflurane and desflurane. Read More

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http://dx.doi.org/10.1111/apt.15168DOI Listing
April 2019
3 Reads

A novel near-infrared fluorescent light-up probe for tumor imaging and drug-induced liver injury detection.

Chem Commun (Camb) 2019 Feb;55(17):2541-2544

State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.

A novel near-infrared fluorescent light-up probe with a tumor-homing pentapeptide, CREKA (Cys-Arg-Glu-Lys-Ala), specifically binds to fibrin-fibronectin complexes was rationally designed and developed for biomedical imaging. Its superior practical applications in tumor imaging and drug-induced liver injury detection are well demonstrated for the first time. Read More

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http://dx.doi.org/10.1039/c8cc10286dDOI Listing
February 2019
6.834 Impact Factor

Assessment of cholestasis in drug-induced liver injury by different methods.

Medicine (Baltimore) 2019 Feb;98(6):e14399

Xiang Yang No 1 Peoples Hospital, Hubei Xiangyang, China.

Cholestasis in drug-induced liver injury (DILI) can be assessed by biochemical and pathologic methods, but the agreement between the 2 methods remains unclear.The aim of this study was to identify the accurate method for assessment of cholestasis in DILI.The DILI standard established and revised by the Council for International Organizations of Medical Sciences (CIOMS) (R values were calculated by liver function at different time points), cholestatic liver disease guideline (European Association for the Study of the Liver, EASL), and liver pathology were used to assess, compare, and analyze the cholestasis in 133 patients with DILI. Read More

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http://dx.doi.org/10.1097/MD.0000000000014399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380790PMC
February 2019
2 Reads
5.723 Impact Factor

Association of FAM65B, AGBL4, and CUX2 genetic polymorphisms with susceptibility to antituberculosis drug-induced hepatotoxicity: validation study in a Chinese Han population.

Pharmacogenet Genomics 2019 Feb 1. Epub 2019 Feb 1.

Departments of Epidemiology.

Objective: Antituberculosis (anti-TB) drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction, and its pathogenic mechanism has not been elucidated thoroughly to date. A recent genome-wide association study reported that seven single-nucleotide polymorphisms (SNPs) in the family with sequence similarity 65, member B gene (FAM65B), ATP/GTP-binding protein-like 4 gene (AGBL4), and cut-like homeobox 2 gene (CUX2) were associated strongly with ATDH in Ethiopian patients. We validated this relationship in a Chinese Han anti-TB treatment population. Read More

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http://dx.doi.org/10.1097/FPC.0000000000000370DOI Listing
February 2019
4 Reads

Preparation and Characterization of Syringic Acid-Loaded TPGS Liposome with Enhanced Oral Bioavailability and In Vivo Antioxidant Efficiency.

AAPS PharmSciTech 2019 Feb 4;20(3):98. Epub 2019 Feb 4.

Center for Nano Drug/Gene Delivery and Tissue Engineering, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, China.

In this study, syringic acid-loaded TPGS liposome (SA-TPGS-Ls) was successfully prepared to improve oral bioavailability of syringic acid (SA). SA is a natural and notable antioxidant activity compound with its limited bioavailability ascribable to its poor aqueous solubility and fast elimination. Recently, TPGS has become a perfect molecular biomaterial in developing several carrier systems with sustained, controlled, and targeted the drug delivery. Read More

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http://dx.doi.org/10.1208/s12249-019-1290-6DOI Listing
February 2019
2 Reads

Synthesis and Biological Evaluation of Some Novel Thiazole-Based Heterocycles as Potential Anticancer and Antimicrobial Agents.

Molecules 2019 Feb 1;24(3). Epub 2019 Feb 1.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, MIU University, Cairo 19648, Egypt.

A novel series of thiazole-based heterocycles was synthesized using 1,3-dipolar cycloaddition reactions in the presence of chitosan-grafted-poly(vinylpyridine) as an eco-friendly biopolymeric basic catalyst. The molecular structure of the synthesized compounds was illustrated by spectroscopic and elemental analysis. Various in vitro biological assays were performed to explore the potential antitumor, antimicrobial and hepatoprotective activities of the newly synthesized compounds. Read More

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http://dx.doi.org/10.3390/molecules24030539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384564PMC
February 2019
1 Read
2.416 Impact Factor

Preventive Effect of Blueberry Extract on Liver Injury Induced by Carbon Tetrachloride in Mice.

Foods 2019 Feb 1;8(2). Epub 2019 Feb 1.

Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing 400067, China.

The blueberry is a common fruit that is rich in nutritional value and polyphenol substances. In this study, the blueberry polyphenol content in extract was analysed by spectrophotometry. The results showed that the blueberry polyphenol content in the extract reached 52. Read More

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http://dx.doi.org/10.3390/foods8020048DOI Listing
February 2019

In vitro protective effect of ascorbic acid against antibiotic-induced hepatotoxicity.

Curr Drug Discov Technol 2019 Feb 4. Epub 2019 Feb 4.

Dept. of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, Kerala. India.

Background: Although antibiotic-induced hepatotoxicity is recoverable with mild impairment, and few of them were reported to cause morbidity. Hence, an adjuvant is essential in reducing such incidences.

Objective: The aim of this study to evaluate the protective effect of ascorbic acid on antibiotic induced liver toxicity using liver slices. Read More

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http://dx.doi.org/10.2174/1570163816666190204122007DOI Listing
February 2019
9 Reads