32,970 results match your criteria Drug-Induced Hepatotoxicity


Payload of T-DM1 binds to cell surface cytoskeleton-associated protein 5 to mediate cytotoxicity of hepatocytes.

Oncotarget 2018 Dec 14;9(98):37200-37215. Epub 2018 Dec 14.

Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, MD, USA.

Off-target toxicity is a major cause of dose-limiting toxicity for antibody-drug conjugates (ADCs), mechanisms of which remain poorly understood. Here, we demonstrate that cytoskeleton-associated protein 5 (CKAP5) serves as a cell surface target for T-DM1 and that binding of T-DM1 to CKAP5 is mediated by payload (DM1). This study introduces a novel molecular mechanism of ADC payload-mediated interaction with cell surface molecules to induce cytotoxicity. Read More

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http://dx.doi.org/10.18632/oncotarget.26461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324681PMC
December 2018

Elevated Transaminases with Topical Diclofenac: A Case Report.

J Pain Palliat Care Pharmacother 2019 Jan 15:1-4. Epub 2019 Jan 15.

Drug-induced liver injury (DILI) has been described with numerous nonsteroidal anti-inflammatory drugs (NSAIDs). Oral diclofenac has been associated with DILI more frequently than other NSAIDs and requires periodic monitoring of liver transaminases and judicious consideration of clinical signs and symptoms of hepatotoxicity. Here we describe a case in which elevated liver transaminases in a 79-year-old female returned to normal following discontinuation of topical diclofenac 1% gel. Read More

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http://dx.doi.org/10.1080/15360288.2018.1546257DOI Listing
January 2019

Systematic Review of Published Data on Herb Induced Liver Injury.

J Ethnopharmacol 2019 Jan 10. Epub 2019 Jan 10.

Liver and Immunology Research Center, Dunsan Oriental Hospital of Daejeon University, 75, Daedeok-daero 176, Seo-gu, Daejeon, Republic of Korea 35253. Electronic address:

Ethnopharmacological Relevance: Herbal products have been widely used as a means of ethnomedicine worldwide. Recently, the potential hepatotoxicity of herbs has become a medical issue but comprehensive studies are limited.

Aim Of The Study: This study aims to determine the clinical features of herb induced liver injury (HILI) including its constituent ratio among liver injury case cohorts that included both HILI and drug induced liver injury (DILI). Read More

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http://dx.doi.org/10.1016/j.jep.2019.01.006DOI Listing
January 2019

A new perspective of triptolide-associated hepatotoxicity: Liver hypersensitivity upon LPS stimulation.

Toxicology 2019 Jan 8. Epub 2019 Jan 8.

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 21009, China. Electronic address:

Objective: This study was designed to investigate whether the mice treated with triptolide (TP) could disrupt the liver immune homeostasis, resulting in the inability of the liver to eliminate the harmful response induced by lipopolysaccharide (LPS). In addition, we explored whether apoptosis and necroptosis played a critical role in the progression of the hepatotoxicity induced by TP-LPS co-treatment.

Methods: Female C57BL/6 mice were continuously administrated with two different doses of TP (250 μg/kg and 500 μg/kg) intragastrically for 7 days. Read More

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http://dx.doi.org/10.1016/j.tox.2019.01.005DOI Listing
January 2019

Differential Hepatotoxic Effects of Sodium Valproate at Different Doses in Albino Rats.

Kathmandu Univ Med J (KUMJ) 2018 Jan.-Mar;16(61):78-82

Department of Anatomy, Kathmandu University School of Medical Sciences, Dhulikhel, Kavre, Nepal.

Background Liver plays an essential role for transforming and clearing chemicals that may cause harmful effects to it. Sodium Valproate, renowned to be a potent antiepileptic drug, when taken in overdose may cause toxic effects to liver and other organs as well. Liver damage can be assessed with histological changes and measurement of enzymes produced by it. Read More

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January 2019

Metabolic profile and hepatoprotective effect of Aeschynomene elaphroxylon (Guill. & Perr.).

PLoS One 2019 10;14(1):e0210576. Epub 2019 Jan 10.

Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Giza, Egypt.

Liver diseases are life-threatening and need urgent medical treatments. Conventional treatment is expensive and toxic, so the urge for nutraceutical hepatoprotective agents is crucial. This study is considered the first metabolic profile of Aeschynomene elaphroxylon (Guill. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210576PLOS
January 2019
3 Reads
3.234 Impact Factor

Exercise Training Prevents Doxorubicin-induced Mitochondrial Dysfunction of the Liver.

Med Sci Sports Exerc 2019 Jan 8. Epub 2019 Jan 8.

Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, SC.

Purpose: Doxorubicin (DOX) is a highly effective chemotherapeutic agent used in the treatment of a broad spectrum of cancers. However, clinical use of DOX is limited by irreversible and dose-dependent hepatotoxicity. The liver is the primary organ responsible for the clearance of antineoplastic agents, and evidence indicates that hepatotoxicity occurs as a result of impaired mitochondrial efficiency during DOX metabolism. Read More

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http://dx.doi.org/10.1249/MSS.0000000000001887DOI Listing
January 2019
3.983 Impact Factor

Protective effect of inulin on methotrexate- induced liver toxicity in mice.

Biomed Pharmacother 2019 Feb;110:943-950

Hyperlipidemia Research Center, Ahvaz, Jundishapur University of Medical Sciences, Ahvaz, Iran.

Methotrexate (MTX) is an effectively used drug in the treatment of cancer and inflammatory diseases but, its use is related with hepatotoxicity. Inulin with antioxidant properties has hepatoprotective effects. In this research, we assessed inulin effects on MTX-induced liver toxicity. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S07533322183580
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http://dx.doi.org/10.1016/j.biopha.2018.11.144DOI Listing
February 2019
5 Reads

Meta-analysis of overall incidence and risk of ALK inhibitors-induced liver toxicities in advanced non-small-cell lung cancer.

Medicine (Baltimore) 2019 Jan;98(1):e13726

Aim: Activation of the anaplastic lymphoma kinase (ALK) gene has been found in several human cancers, including non-small-cell lung cancer (NSCLC). Currently, novel drugs targeting ALK gene have been extensively investigated in NSCLC. However, concerns about ALK inhibitors-induced liver toxicities have been increasing. Read More

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http://Insights.ovid.com/crossref?an=00005792-201901040-0000
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http://dx.doi.org/10.1097/MD.0000000000013726DOI Listing
January 2019
1 Read

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

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

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

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

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http://dx.doi.org/10.3390/molecules24010110DOI Listing
December 2018
2.416 Impact Factor

Hepatotoxicity induced by psoralen and isopsoralen from Fructus Psoraleae: Wistar rats are more vulnerable than ICR mice.

Food Chem Toxicol 2018 Dec 28;125:133-140. Epub 2018 Dec 28.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, PR China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, PR China. Electronic address:

Fructus Psoraleae (FP) causes cholestatic liver injury; however, its main toxic constituents that are responsible for causing hepatotoxicity remained undetermined in previous studies. In the present study, psoralen and isopsoralen, the two main constituents of FP, were administered orally to rats (80 and 40 mg/kg, respectively) and mice (320 and 160 mg/kg, respectively) for 28 days, followed by biochemical and histopathological examinations to evaluate their hepatotoxicity. The results showed that psoralen and isopsoralen could induce the toxic reactions of liver and other organs in rats, while mice were not sensitive to these two compounds. Read More

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http://dx.doi.org/10.1016/j.fct.2018.12.047DOI Listing
December 2018

Evaluation of naproxen-induced oxidative stress, hepatotoxicity and genotoxicity in male Wistar rats.

J Pharm Anal 2018 Dec 20;8(6):400-406. Epub 2018 Apr 20.

School of Life Sciences, Jawaharlal Nehru University (JNU), New Delhi 110067, India.

Naproxen (NP), a nonsteroidal anti-inflammatory drug (NSAID), is used for the treatment of common pain, inflammation and tissue damage. Genotoxicity testing of NP is of prime importance as it represents the largest group of drugs to which humans are exposed. Not many genotoxic studies are reported on NP; therefore, the present study investigated the detailed genotoxic and oxidative stress properties of NP. Read More

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http://dx.doi.org/10.1016/j.jpha.2018.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308023PMC
December 2018

LC and LC-MS/MS studies for the identification and characterization of degradation products of acebutolol.

J Pharm Anal 2018 Dec 15;8(6):357-365. Epub 2018 Mar 15.

Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India.

The aim of the present investigation was to demonstrate an approach involving use of liquid chromatography (LC) and liquid chromatography-mass spectrometry (LC-MS) to separate, identify and characterize very small quantities of degradation products (DPs) of acebutolol without their isolation from the reaction mixtures. The drug was subjected to oxidative, hydrolytic, thermal and photolytic stress conditions as per International Conference on Harmonization (ICH) guideline Q1A(R2). Among all the stress conditions the drug was found to be labile in hydrolytic (acidic & basic) and photolytic stress conditions, while it was stable in water-induced hydrolysis, oxidative and thermal stress conditions. Read More

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http://dx.doi.org/10.1016/j.jpha.2018.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308026PMC
December 2018

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

J Pharmacol Toxicol Methods 2018 Dec 27. Epub 2018 Dec 27.

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

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

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

Recapitulation of methotrexate hepatotoxicity with induced pluripotent stem cell-derived hepatocytes from patients with rheumatoid arthritis.

Stem Cell Res Ther 2018 Dec 29;9(1):357. Epub 2018 Dec 29.

CiSTEM laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Republic of Korea.

Background: Methotrexate (MTX) is widely used for the treatment of rheumatoid arthritis (RA). The drug is cost-effective, but sometimes causes hepatotoxicity, requiring a physician's attention. In this study, we simulated hepatotoxicity by treating hepatocytes derived from RA patient-derived induced pluripotent stem cells (RA-iPSCs) with MTX. Read More

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http://dx.doi.org/10.1186/s13287-018-1100-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310944PMC
December 2018

Cytoprotective effects of molsidomine against methotrexate-induced hepatotoxicity: an experimental rat study.

Drug Des Devel Ther 2019 20;13:13-21. Epub 2018 Dec 20.

Department of Pharmacology, Inonu University School of Medicine, Malatya, Turkey.

Introduction And Aim: Methotrexate (Mtx) is an antineoplastic and immunosuppressive drug that may cause hepatotoxicity, whereas molsidomine (Mol) is a vasodilating and antioxidant agent. This study aimed to investigate the potential protective effects of Mol in Mtx-induced liver toxicity in rats.

Materials And Methods: Forty Wistar albino rats were equally divided into five groups: control, Mol, Mtx, Mol-Mtx, and Mtx-Mol. Read More

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http://dx.doi.org/10.2147/DDDT.S181550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304250PMC
December 2018

Phytochemical analysis and hepatoprotective effect of polyherbal formulation on CCl4 induced hepatotoxicity in mice.

Pak J Pharm Sci 2018 Nov;31(6 (Supplementary):2719-2723

Department of Pathology, Faculty of Medical and Health Sciences, University of Sargodha, Sargodha, Pakistan.

The potent phytotherapeutic modalities against the hepatotoxicity have motivated us to explore numerous plants and polyherbal preparations because conventional drug discovery is more expensive and tedious. So, this study was conducted to evaluate the hepatoprotective potential of a polyherbal formulation (PHF), comprising of Solanum nigrum, Silybum marianum, Atrmesia absinthium, Achillea millifolium and Cichorium intybus against carbon tetrachloride(CCl4) induced hepatotoxicity in experimental rats. CCl4intoxicationinduced vacuole formation and fastdegeneration so selective liver enzymes including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alkalinephosphatase (ALP) and total bilirubin in rat's plasma,as well as liver histological architecture, were used to evaluate the effect of herbal treatments with different doses (ranging 100-500 mg/kg) for two weeks. Read More

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November 2018
1 Read

Protocatechuic acid protects against menadione-induced liver damage by up-regulating nuclear erythroid-related factor 2.

Drug Chem Toxicol 2018 Dec 26:1-7. Epub 2018 Dec 26.

b Antioxidants, Redox Biology and Toxicology Research Laboratory, Department of Medical Biochemistry, College of Health Sciences , Nile University of Nigeria , Abuja , Nigeria.

Menadione (Vitamin K) is an over-the-counter (OTC) drug used in the treatment of abdominal cramps, colitis, diarrhea, hay fever, hemorrahage, hypoprothrombinemia, and joint pains. In this study, we evaluated the protective influence of protocatechuic acid on menadione-induced hepatotoxicity in rats. Rats were randomized into five groups (A-E) of five rats each. Read More

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http://dx.doi.org/10.1080/01480545.2018.1523187DOI Listing
December 2018

Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association.

Arterioscler Thromb Vasc Biol 2018 Dec 10:ATV0000000000000073. Epub 2018 Dec 10.

One in 4 Americans >40 years of age takes a statin to reduce the risk of myocardial infarction, ischemic stroke, and other complications of atherosclerotic disease. The most effective statins produce a mean reduction in low-density lipoprotein cholesterol of 55% to 60% at the maximum dosage, and 6 of the 7 marketed statins are available in generic form, which makes them affordable for most patients. Primarily using data from randomized controlled trials, supplemented with observational data where necessary, this scientific statement provides a comprehensive review of statin safety and tolerability. Read More

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http://dx.doi.org/10.1161/ATV.0000000000000073DOI Listing
December 2018
3 Reads

n-3 Polyunsaturated fatty acids for the management of alcoholic liver disease: A critical review.

Crit Rev Food Sci Nutr 2018 Dec 22:1-14. Epub 2018 Dec 22.

a State Key Laboratory of Quality Research in Chinese Medicine , Institute of Chinese Medical Sciences, University of Macau , Macao , China.

Excess alcohol exposure leads to alcoholic liver disease (ALD), a predominant cause of liver-related morbidity and mortality worldwide. In the past decade, increasing attention has been paid to understand the association between n-3 polyunsaturated fatty acids (n-3 PUFAs) and ALD. In this review, we summarize the metabolism of n-3 PUFAs, animal model of ALD, and the findings from recent studies determining the role of n-3 PUFAs in ALD as a possible treatment. Read More

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https://www.tandfonline.com/doi/full/10.1080/10408398.2018.1
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http://dx.doi.org/10.1080/10408398.2018.1544542DOI Listing
December 2018
4 Reads

Efficacy Evaluation of High-Dose Atorvastatin Pretreatment in Patients with Acute Coronary Syndrome: A Meta-Analysis of Randomized Controlled Trials.

Med Sci Monit 2018 Dec 23;24:9354-9363. Epub 2018 Dec 23.

Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jianghsu, China (mainland).

BACKGROUND It is unclear whether high-dose atorvastatin pretreatment benefits acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). To clarify this issue, we performed a meta-analysis of the published literature. MATERIAL AND METHODS Randomized controlled trials (RCTs) assessing high-dose atorvastatin pretreatment in ACS patients undergoing PCI were enrolled. Read More

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http://dx.doi.org/10.12659/MSM.912544DOI Listing
December 2018
1 Read

Patients with Chronic Liver Disease Suggestive of Nonalcoholic Fatty Liver Disease may be at Higher Risk for Drug Induced Liver Injury.

Clin Gastroenterol Hepatol 2018 Dec 20. Epub 2018 Dec 20.

Department of Medicine, Indiana University School of Medicine, Indianapolis, IN. Electronic address:

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https://linkinghub.elsevier.com/retrieve/pii/S15423565183138
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http://dx.doi.org/10.1016/j.cgh.2018.12.013DOI Listing
December 2018
3 Reads

Genetic depletion of p53 attenuates cocaine-induced hepatotoxicity in mice.

Biochimie 2018 Dec 18;158:53-61. Epub 2018 Dec 18.

Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea. Electronic address:

Cocaine, an addictive drug, is known to induce hepatotoxicity via oxidative damage and proapoptosis. Since p53, a tumor suppressor gene, plays a major role in inducing oxidative stress and apoptosis, we examined the role of p53 inhibition against cocaine-induced hepatotoxicity. Cocaine treatment significantly increased oxidative parameters (i. Read More

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http://dx.doi.org/10.1016/j.biochi.2018.12.009DOI Listing
December 2018
1 Read
2.963 Impact Factor

The deleterious effects of N,N-dimethylformamide on liver: A mini-review.

Chem Biol Interact 2019 Jan 18;298:129-136. Epub 2018 Dec 18.

Institute of Toxicology, School of Public Health, Shandong University, PR China. Electronic address:

N,N-dimethylformamide (DMF) is a versatile solvent with wide industrial applications. Evidences from animal studies and occupational poisoning cases have clearly demonstrated that DMF exposure can lead to different degrees of liver damage. It is noteworthy that DMF below the threshold limit value (TLV) may also cause liver injury in some sensitive populations. Read More

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http://dx.doi.org/10.1016/j.cbi.2018.12.011DOI Listing
January 2019

Symptomatic treatment of dengue: Should the NSAID contraindication be reconsidered?

Postgrad Med 2018 Dec 21. Epub 2018 Dec 21.

b Pfizer Consumer Healthcare , Sao Paulo , Brazil.

Consensus guidelines for treatment of dengue fever from the World Health Organization and US Centers for Disease Control recommend acetaminophen to manage pain and fever but contraindicate nonsteroidal anti-inflammatory agents (NSAIDs) because of potentially increased bleeding risk, with thrombocytopenia as a complication. Neither acetaminophen nor ibuprofen (the NSAID with lowest bleeding risk) have been evaluated for dengue treatment in randomized, controlled clinical trials. Epidemiologic and cohort studies and case series describing NSAID use in dengue generally point to minimal or no significant increase in bleeding risk, except for aspirin. Read More

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https://www.tandfonline.com/doi/full/10.1080/00325481.2019.1
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http://dx.doi.org/10.1080/00325481.2019.1561916DOI Listing
December 2018
2 Reads

Assessment of hepatotoxicity and dermal toxicity of butyl paraben and methyl paraben using HepG2 and HDFn in vitro models.

Toxicol In Vitro 2019 Mar 17;55:108-115. Epub 2018 Dec 17.

School of Engineering, Newcastle University, Newcastle Upon Tyne, United Kingdom. Electronic address:

Parabens, esters of parahydroxybenzoic acid, are widely used in cosmetic, food and pharmaceutical industries mainly for their antibacterial and fungicidal properties. Methyl paraben has shown very low toxicity in a wide range of in vitro and animal tests. However, butyl paraben and derivatives, such as isobutyl parabens, are classified as allergens and have been shown to induce toxic effects. Read More

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http://dx.doi.org/10.1016/j.tiv.2018.12.007DOI Listing

Mechanistic Approach for Thioridazine-Induced Hepatotoxicity and Potential Benefits of Melatonin and/or Coenzyme Q10 on Freshly Isolated Rat Hepatocytes.

Iran J Pharm Res 2018 ;17(4):1465-1475

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Thioridazine (TZ) is used mainly in the treatment of schizophrenia. However, hepatotoxicity as a life-threatening adverse effect is associated with its clinical use. In this context, we examined the cytotoxic mechanisms of TZ on freshly isolated rat hepatocytes to better understanding of the pathogenesis of TZ-induced hepatotoxicity. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269589PMC
January 2018

Schisandrin B elicits the Keap1-Nrf2 defense system via carbene reactive metabolite which is less harmful to mice liver.

Drug Des Devel Ther 2018 23;12:4033-4046. Epub 2018 Nov 23.

College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Beibei, Chongqing 400715, China,

Background: Schisandrin B (Sch B) a main active component of , has been shown to act as a liver protectant via activation of the Nrf2 pathway. Nevertheless, it remains unclear whether its reactive metabolite is responsible for Nrf2 activation; also, the effects of its reactive metabolite on liver function are still unknown.

Methods: The present study determined and identifed the carbene reactive metabolite of Sch B in human and mice liver microsomes. Read More

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http://dx.doi.org/10.2147/DDDT.S176561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267698PMC
November 2018

Tamoxifen-induced hepatotoxicity caused by drug interaction with direct-acting antiviral agents for hepatitis C.

J Oncol Pharm Pract 2018 Dec 18:1078155218819742. Epub 2018 Dec 18.

1 Department of Hepatogastroenterology, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

A 68-year-old man develops acute hepatocellular injury during treatment with direct-acting antiviral agents (DAA) for hepatitis C. Medical history reveals the intake of tamoxifen as adjuvant treatment for breast cancer, currently in remission. After stopping tamoxifen, despite the continuation of the anti-HCV agents, a complete resolution of liver injury occurs. Read More

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http://dx.doi.org/10.1177/1078155218819742DOI Listing
December 2018

Mechanisms of Inflammatory Liver Injury and Drug-Induced Hepatotoxicity.

Curr Pharmacol Rep 2018 Oct 30;4(5):346-357. Epub 2018 Jun 30.

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

Purpose Of Review: This article provides a brief overview of mechanisms of inflammatory liver injury and how this applies to drug hepatotoxicity with a particular emphasis on the role of inflammation in acetaminophen-induced liver injury.

Recent Findings: Significant progress has been made in the last decade in our understanding of the initiation of sterile inflammation after necrotic cell death by the release of damage-associated molecular patterns and their recognition by toll-like receptors and others on macrophages. These events trigger the formation of cytokines and chemokines directly or with assistance of inflammasome activation thereby activating and recruiting leukocytes including neutrophils and monocyte-derived macrophages into the necrotic areas. Read More

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http://link.springer.com/10.1007/s40495-018-0147-0
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http://dx.doi.org/10.1007/s40495-018-0147-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294466PMC
October 2018
4 Reads

Quercetin and Idebenone Ameliorate Oxidative Stress, Inflammation, DNA damage, and Apoptosis Induced by Titanium Dioxide Nanoparticles in Rat Liver.

Dose Response 2018 Oct-Dec;16(4):1559325818812188. Epub 2018 Dec 9.

Common First Year Deanship, King Saud University, Riyadh, Saudi Arabia.

Titanium dioxide nanoparticles (TiO-NPs) are extensively used in a wide range of applications; however, many reports have investigated their nanotoxicological effect at the molecular level either in vitro or in vivo systems. The defensive roles of quercetin (Qur) or idebenone (Id) against the hepatotoxicity induced by TiO-NPs were evaluated in the current study. The results showed that the coadministration of Qur or Id to rats intoxicated with TiO-NPs markedly ameliorated the elevation in hepatic malondialdehyde (MDA), serum alanine amino-transferase (ALT), glucose, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), immunoglobin G (IgG), and C-reactive protein (CRP) levels compared to their levels in TiO-NPs-treated rats. Read More

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http://dx.doi.org/10.1177/1559325818812188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291876PMC
December 2018
2 Reads
1.234 Impact Factor

Fucoidan Alleviates Acetaminophen-Induced Hepatotoxicity via Oxidative Stress Inhibition and Nrf2 Translocation.

Int J Mol Sci 2018 Dec 14;19(12). Epub 2018 Dec 14.

Department of Pharmacology, School of Pharmacy and Key Laboratory of Inflammation and Molecular Drug Target of Jiangsu Province, Nantong University, Nantong 226001, China.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that leads to severe hepatotoxicity at excessive doses. Fucoidan, a sulfated polysaccharide derived from brown seaweeds, possesses a wide range of pharmacological properties. However, the impacts of fucoidan on APAP-induced liver injury have not been sufficiently addressed. Read More

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http://dx.doi.org/10.3390/ijms19124050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321350PMC
December 2018
2.862 Impact Factor

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

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

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

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

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

Telfairia occidentalis (Cucurbitaceae) pulp extract mitigates rifampicin-isoniazid-induced hepatotoxicity in an in vivo rat model of oxidative stress.

J Integr Med 2019 Jan 1;17(1):46-56. Epub 2018 Dec 1.

Medical Laboratory Sciences, Faculty of Basic Medical Sciences, College of Health Sciences, Niger Delta University, Amassoma, PMB 071 Yenegoa, Bayelsa State, Nigeria.

Objective: Drug-induced liver injury complicates antituberculosis drug treatment and is a leading cause of death worldwide. The aim of this study is to establish the ethnomedicinal claim of hepatoprotective effects of fruit pulp extract of Telfairia occidentalis against rifampicin (RIF) and isoniazid (INH)-induced oxidative stress in rats.

Methods: T. Read More

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http://dx.doi.org/10.1016/j.joim.2018.11.008DOI Listing
January 2019

Dimethyl fumarate ameliorates acetaminophen-induced hepatic injury in mice dependent of Nrf-2/HO-1 pathway.

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

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

Drug-induced liver toxicity is the most frequent cause of acute liver failure worldwide. Hepatotoxicity caused by acetaminophen (ACT) overdose is mediated by its metabolic product promoting oxidative stress and activation of inflammatory mediators. Nuclear factor erythroid-related factor-2 (Nrf-2) induces the release of cytoprotective enzymes in response to electrophilic or oxidative stress and is considered a promising therapeutic target. Read More

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http://dx.doi.org/10.1016/j.lfs.2018.12.013DOI Listing
January 2019
1 Read

The diagnostic role of miR-122 in drug-induced liver injury: A systematic review and meta-analysis.

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

School of Graduates, Tianjin Medical University.

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

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

Pterostilbene protects against acetaminophen-induced liver injury by restoring impaired autophagic flux.

Food Chem Toxicol 2019 Jan 10;123:536-545. Epub 2018 Dec 10.

School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Republic of Korea. Electronic address:

An overdose of acetaminophen (APAP) causes liver injury through formation of N-acetyl-p-benzoquinoneimine, which overproduces reactive oxygen species (ROS). Autophagy maintains cellular homeostasis and is regulated by generation of ROS. Pterostilbene (PTE) has been shown to have antioxidant and anti-inflammatory properties. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02786915183088
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http://dx.doi.org/10.1016/j.fct.2018.12.012DOI Listing
January 2019
3 Reads

Drp1-associated mitochondrial dysfunction and mitochondrial autophagy: a novel mechanism in triptolide-induced hepatotoxicity.

Cell Biol Toxicol 2018 Dec 13. Epub 2018 Dec 13.

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

Triptolide being an active ingredient of Chinese herbal plant Tripterygium wilfordii Hook f. has severe hepatotoxicity. Previous studies from our lab reported triptolide-induced mitochondrial toxicity in hepatocytes. Read More

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http://dx.doi.org/10.1007/s10565-018-9447-8DOI Listing
December 2018
2.677 Impact Factor

Assessment of Incidence and Character of Neurologic/ Neuropsychiatric Complications in a Group of Patients with Malignant Melanoma Treated with Adjuvant High Dose Interferon.

Klin Onkol 2018 ;31(5):361-365

Background: Authors describe the incidence and character of neurologic and neuropsychiatric complications - particularly depression and parkinsonism - during adjuvant treatment of malignant melanoma (MM) with high dose interferon (HDI). Among the most frequently observed side effects are fatigue, hematotoxicity, and hepatotoxicity. Most research has been directed at depression and parkinsonism because of the lack of literature concerning these complications. Read More

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http://dx.doi.org/10.14735/amko2018361DOI Listing
January 2018

Clinical factors predicting drug-induced liver injury due to flucloxacillin.

Drug Healthc Patient Saf 2018 21;10:95-101. Epub 2018 Nov 21.

Department of Medical Sciences, Clinical Pharmacology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden,

Objectives: Drug-induced liver injury (DILI) is a serious adverse reaction due to flucloxacillin. The pathogenesis is not fully understood. Female sex, age over 60 years, and a longer treatment duration have been suggested to be predisposing factors. Read More

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http://dx.doi.org/10.2147/DHPS.S178394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254585PMC
November 2018
1 Read

Potential effects of different natural antioxidants on inflammatory damage and oxidative-mediated hepatotoxicity induced by gold nanoparticles.

Int J Nanomedicine 2018 23;13:7931-7938. Epub 2018 Nov 23.

Department of Physics and Astronomy, College of Science, King Saud University, Riyadh, Saudi Arabia,

Objective: The objective of this study was to verify and confirm the oxidative-mediated hepatotoxicity, inflammatory liver damage, and oxidative stress induced by intraperitoneal administration of gold nanoparticles (GNPs) in vivo; characterize the effect of different natural antioxidants on these hazardous changes; and finally choose the most powerful antioxidant among these different natural antioxidants.

Methods: Ten-nanometer GNPs were dissolved in aqueous solution of 0.01% concentration. Read More

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http://dx.doi.org/10.2147/IJN.S171931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260143PMC
January 2019
1 Read

Mechanistic insights of hepatoprotective effects of curcumin: Therapeutic updates and future prospects.

Food Chem Toxicol 2018 Dec 5;124:182-191. Epub 2018 Dec 5.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

The liver is the most essential organ of the body performing vital functions. Hepatic disorders affect the physiological and biochemical functions of the body. These disorders include hepatitis B, hepatitis C, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), liver cirrhosis, hepatic failure and hepatocellular carcinoma (HCC). Read More

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http://dx.doi.org/10.1016/j.fct.2018.12.002DOI Listing
December 2018
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Evaluation of In Vitro Mitochondrial Toxicity Assays and Physicochemical Properties for Prediction of Organ Toxicity Using 228 Pharmaceutical Drugs.

Chem Res Toxicol 2018 Dec 10. Epub 2018 Dec 10.

Mitochondrial toxicity has been shown to contribute to a variety of organ toxicities such as liver, cardiac and kidney. In the past decades, two high throughput applicable screening assays (isolated rat liver mitochondria; glucose-galactose grown HepG2 cells) to assess mitochondrial toxicity have been deployed in many pharmaceutical companies and numerous publications have demonstrated its usefulness for mechanistic investigations. However, only two publications have demonstrated the utility of these screens as a predictor of human drug induced liver injury. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.8b00246DOI Listing
December 2018
1 Read

Ganoderic acid A against cyclophosphamide-induced hepatic toxicity in mice.

J Biochem Mol Toxicol 2018 Dec 1:e22271. Epub 2018 Dec 1.

Department of Hepatology, Nantong Third People's Hospital, Nantong University, Nantong, China.

This study clarified the protective effect of ganoderic acid A (GAA) on cyclophosphamide (CP)-induced hepatotoxicity in mice. Hepatic injury mice were induced by a single intraperitoneal injection of CP (200 mg/kg). The results showed that the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and liver of the CP group mice were increased, and the levels of cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in serum were increased. Read More

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http://doi.wiley.com/10.1002/jbt.22271
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http://dx.doi.org/10.1002/jbt.22271DOI Listing
December 2018
17 Reads

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

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

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

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

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

Revised Antituberculosis Drug Doses and Hepatotoxicity in HIV Negative Children.

Indian J Pediatr 2018 Dec 4. Epub 2018 Dec 4.

Department of Pediatrics, St John's Medical College Hospital, Bengaluru, Karnataka, India.

Objectives: To compare the incidence of anti tuberculosis drug-induced hepatotoxicity (ATDH) with those on old vs. revised WHO doses in human immunodeficiency virus (HIV) negative children. The secondary objective was to determine the overall incidence of hepatitis in children on Anti tubercular treatment (ATT) and isoniazid prophylactic therapy (IPT). Read More

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http://link.springer.com/10.1007/s12098-018-2812-z
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http://dx.doi.org/10.1007/s12098-018-2812-zDOI Listing
December 2018
4 Reads

Enhanced Regeneration and Hepatoprotective Effects of Interleukin 22 Fusion Protein on a Predamaged Liver Undergoing Partial Hepatectomy.

J Immunol Res 2018 31;2018:5241526. Epub 2018 Oct 31.

Department of Geriatrics, Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, China.

Liver ischemia-reperfusion injury (IRI) and regeneration deficiency are two major challenges for surgery patients with chronic liver disease. As a survival factor for hepatocytes, interleukin 22 (IL-22) plays an important role in hepatoprotection and the promotion of regeneration after hepatectomy. In this study, we aim to investigate the roles of an interleukin 22 fusion protein (IL-22-FP) in mice with a predamaged liver after a two-third partial hepatectomy (PHx). Read More

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https://www.hindawi.com/journals/jir/2018/5241526/
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http://dx.doi.org/10.1155/2018/5241526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234454PMC
January 2019
5 Reads

Embracing the Dark Side: Computational Approaches to Unveil the Functionality of Genes Lacking Biological Annotation in Drug-Induced Liver Injury.

Front Genet 2018 20;9:527. Epub 2018 Nov 20.

Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, Netherlands.

In toxicogenomics, functional annotation is an important step to gain additional insights into genes with aberrant expression that drive pathophysiological mechanisms. Nevertheless, there exists a gap on annotation of these genes which often hampers the interpretation of results and limits their applicability in translational medicine. In this study, we evaluated the coverage of functional annotations of differentially expressed genes (DEGs) induced by 10 selected compounds from the TG-GATEs database identified as high- or no-risk in causing drug-induced liver injury (most-DILI or no-DILI, respectively) using human data. Read More

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http://dx.doi.org/10.3389/fgene.2018.00527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255978PMC
November 2018
3 Reads

Development of a novel rat model of heterogeneous hepatic injury by injection with colchicine the splenic vein.

World J Gastroenterol 2018 Nov;24(44):5005-5012

Department of Radiology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.

Aim: To develop a novel rat model of heterogeneous hepatic injury.

Methods: Seventy male Sprague-Dawley rats were randomly divided into a control group ( = 10) and a colchicine group ( = 60). A 0. Read More

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http://dx.doi.org/10.3748/wjg.v24.i44.5005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262251PMC
November 2018

Pharmacogenetic association between gene polymorphisms and isoniazid induced hepatotoxicity: trial sequence meta-analysis as evidence.

Biosci Rep 2019 Jan 15;39(1). Epub 2019 Jan 15.

Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan 45142, Saudi Arabia

Hepatotoxicity is a severe problem generally faced by tuberculosis (TB) patients. It is a well-known adverse reaction due to anti-TB drugs in TB patients undergoing long-term treatment. The studies published previously have explored the connection of N-acetyltransferase 2 () gene polymorphisms with isoniazid-induced hepatotoxicity, but the results obtained were inconsistent and inconclusive. Read More

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http://dx.doi.org/10.1042/BSR20180845DOI Listing
January 2019
2.637 Impact Factor