35,554 results match your criteria Drug-Induced Hepatotoxicity


Tanshinone IIA attenuates acetaminophen-induced hepatotoxicity through HOTAIR-Nrf2-MRP2/4 signaling pathway.

Biomed Pharmacother 2020 Aug 7;130:110547. Epub 2020 Aug 7.

Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address:

Tanshinone IIA (Tan IIA), an active component in S. miltiorrhiza, has been reported to have excellent antioxidant and detoxifying activity. Here, we prove that Tan IIA attenuates acetaminophen-induced hepatotoxicity from a pharmacokinetic perspective. Read More

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http://dx.doi.org/10.1016/j.biopha.2020.110547DOI Listing

Leaf and root bark extracts of Ziziphus abyssinica Hochst ex. A. Rich (Rhamnaceae) ameliorate hepatic, renal and splenic injuries induced by phenylhydrazine in rats.

J Basic Clin Physiol Pharmacol 2020 Aug 3. Epub 2020 Aug 3.

Department of Pharmacology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana.

Objectives Ziziphus abyssinica (ZA) is employed in managing several ailments in Traditional African Medicine. Scientific evaluations are necessary to ascertain the medicinal potential of ZA as a source of new drug molecules. This study investigated the possible therapeutic benefit of ZA leaf (ZAL) and root bark (ZARB) extracts in an experimental model of multi-organ injuries induced by phenylhydrazine (PHZ). Read More

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http://dx.doi.org/10.1515/jbcpp-2020-0111DOI Listing

L.-induced hepatotoxicity and involvement of metabolic activation of furanoterpenoids.

Drug Metab Rev 2020 Aug 6:1-17. Epub 2020 Aug 6.

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, China.

The rhizome of L. (DBL) is a popular traditional herb in the treatment of goiters, breast lumps, and tumors. Unfortunately, DBL can give rise to severe hepatotoxicity. Read More

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http://dx.doi.org/10.1080/03602532.2020.1800724DOI Listing

DNA damage and genetic aberration induced via different sized silver nanoparticles: Therapeutic approaches of Casimiroa edulis and Glycosmis pentaphylla leaves extracts.

J Food Biochem 2020 Aug 4:e13398. Epub 2020 Aug 4.

Departments of Pharmacognosy, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Giza, Egypt.

Potential of Casimiroa edulis and Glycosmis pentaphylla leaves extracts were investigated against the effect of two different particle sizes of silver nanoparticles induced toxicity in mice. Mice received silver nanoparticles (AgNPs) (100 mg/kg) with 20 and 100 nm for four weeks followed by daily oral dose of extracts (500 mg/kg) for three weeks. C. Read More

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http://dx.doi.org/10.1111/jfbc.13398DOI Listing
August 2020
0.741 Impact Factor

The effects of chard on brain damage in valproic acid-induced toxicity.

J Food Biochem 2020 Aug 4:e13382. Epub 2020 Aug 4.

Faculty of Engineering, Department of Chemistry, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Valproic acid (VPA; 2-propyl valeric acid) is a potent drug widely used in treating anxiety disorders, migraine as well as epileptic diseases. In the ongoing study chard protective effect was investigated, on the damaged VPA rat brain. Sprague Dawley rats (females) were grouped as follows: control, VPA (500 mg kg  day VPA intraperitoneal), chard (100 mg/kg day chard extract by gavage), VPA + chard (500 mg kg  day VPA + 100 mg kg  day chard extract). Read More

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http://dx.doi.org/10.1111/jfbc.13382DOI Listing

Nilotinib-Induced Immune-Mediated Liver Injury: Corticosteroid as a Possible Therapeutic Option.

Front Oncol 2020 10;10:1160. Epub 2020 Jul 10.

Division of Hematology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.

Nilotinib is a BCR-ABL tyrosine kinase inhibitor approved for chronic myeloid leukemia. We present a case of severe immune-mediated liver injury by nilotinib treatment. A 59-year-old woman was referred to the liver clinic because of elevated liver enzyme levels. Read More

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http://dx.doi.org/10.3389/fonc.2020.01160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367179PMC

Liver Injury with Ulipristal Acetate: Exploring the Underlying Pharmacological Basis.

Drug Saf 2020 Aug 3. Epub 2020 Aug 3.

Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy.

Introduction: The European Medicines Agency has suspended the use of ulipristal acetate (UPA) in the treatment of uterine fibroids and is reassessing its association with a risk of liver injury.

Objectives: Our objectives were to characterize the post-marketing reporting of drug-induced liver injury (DILI) with UPA and investigate the underlying pharmacological basis.

Methods: We queried the worldwide FDA Adverse Event Reporting System and performed a disproportionality analysis, selecting only hepatic designated medical events (DMEs) where UPA was reported as suspect. Read More

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http://dx.doi.org/10.1007/s40264-020-00975-8DOI Listing

Current etiological comprehension and therapeutic targets of acetaminophen-induced hepatotoxicity.

Pharmacol Res 2020 Jul 29:105102. Epub 2020 Jul 29.

School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address:

Acetaminophen (APAP) is the most popular mild analgesic and antipyretic drug used worldwide. APAP overdose leads to drug-induced hepatotoxicity and can cause hepatic failure if treatment delayed. It is adequately comprehended that the metabolism of high-dose APAP by cytochrome P450 enzymes generates N-acetyl-p-benzoquinone imine (NAPQI), a toxic metabolite, which leads to glutathione (GSH) depletion, oxidative stress, and activation of various complex molecular pathways that initiate liver injury and downstream hepatic necrosis. Read More

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http://dx.doi.org/10.1016/j.phrs.2020.105102DOI Listing

The utility of a differentiated preclinical liver model, HepaRG cells, in investigating delayed toxicity via inhibition of mitochondrial-replication induced by fialuridine.

Toxicol Appl Pharmacol 2020 Jul 28;403:115163. Epub 2020 Jul 28.

MRC Centre for Drug Safety Science, The Department of Pharmacology and Therapeutics, The University of Liverpool, Ashton Street, Liverpool L69 3GE, UK. Electronic address:

During its clinical development fialuridine caused liver toxicity and the death of five patients. This case remains relevant due to the continued development of mechanistically-related compounds against a back-drop of simple in vitro models which remain limited for the preclinical detection of such delayed toxicity. Here, proteomic investigation of a differentiated, HepaRG, and proliferating, HepG2 cell model was utilised to confirm the presence of the hENT1 transporter, thymidine kinase-1 and -2 (TK1, TK2) and thymidylate kinase, all essential in order to reproduce the cellular activation and disposition of fialuridine in the clinic. Read More

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http://dx.doi.org/10.1016/j.taap.2020.115163DOI Listing

Effects of medium- and long-chain fatty acids on acetaminophen- or rifampicin-induced hepatocellular injury.

Food Sci Nutr 2020 Jul 19;8(7):3590-3601. Epub 2020 May 19.

State Key Laboratory of Food Science and Technology Nanchang University Nanchang China.

Drug-induced liver injury (DILI) is one of the common adverse effects of drug therapy, which is closely associated with oxidative stress, apoptosis, and inflammation response. Medium-chain fatty acids (MCFA) were reported to relieve inflammation and attenuate oxidative stress. However, little has been known about the hepatoprotective effects of MCFA in DILI. Read More

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http://dx.doi.org/10.1002/fsn3.1641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382196PMC

Multi-omics profiling reveals protective function of Schisandra lignans against acetaminophen-induced hepatotoxicity.

Drug Metab Dispos 2020 Jul 27. Epub 2020 Jul 27.

Key Lab of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, China

The action principles of traditional Chinese medicines (TCMs) feature multi-active components, multi-target sites, and weak combination with action targets. In the present study, we performed an integrated analysis of metabonomics, proteomics and lipidomics to establish a scientific research system on the underlying mechanism of TCMs, and Schisandra lignan extract (SLE) was selected as a model TCM. In metabonomics, several metabolic pathways were found to mediate the liver injury induced by acetaminophen (APAP), and SLE could regulate the disorder of lipid metabolism. Read More

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http://dx.doi.org/10.1124/dmd.120.000083DOI Listing

Metabolomics analysis of plasma reveals voriconazole-induced hepatotoxicity is associated with oxidative stress.

Toxicol Appl Pharmacol 2020 Jul 25;403:115157. Epub 2020 Jul 25.

School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Voriconazole is one of the most frequently used antifungal drugs for the initial treatment of invasive aspergillosis, but liver-related adverse events occur frequently and usually lead to drug discontinuation. Moreover, the mechanism of voriconazole-induced hepatotoxicity remains unsettled. A holistic understanding of its mechanism is critical to prevent liver-related adverse events. Read More

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http://dx.doi.org/10.1016/j.taap.2020.115157DOI Listing

Evidence of drug-induced hepatotoxicity in the Maghrebian population.

Drug Chem Toxicol 2020 Jul 26:1-5. Epub 2020 Jul 26.

Faculty of Medicine and Pharmacy, Laboratory of Chemistry-Biochemistry, Environment, Nutrition, and Health, Hassan II University, Casablanca, Morocco.

Drug-induced hepatotoxicity is one of the most challenging hepatic diseases faced nowadays due to a large number of drugs currently used in clinical practice, the enormous dietary supplements which are potentially hepatotoxic, as well as the ability to appear with different clinical symptoms and the absence of specific markers. The current research survey was conducted to investigate drug-induced hepatotoxicity and demographic characteristics of patients with liver damage in the general Maghrebian population between 1992 and 2018. To achieve this goal a questionnaire was adopted to report details on the undesirable effects of drugs and demographic characteristics of affected patients. Read More

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http://dx.doi.org/10.1080/01480545.2020.1797088DOI Listing

Late Diagnosis of Paracetamol Poisoning is Always Lethal in Young Adult.

J Coll Physicians Surg Pak 2020 Jun;30(6):655-658

Department of Chemical Pathology and Endocrinology, AFIP, National University of Medical Sciences, Rawalpindi, Pakistan.

Acetaminophen has a remarkable safety profile when prescribed in proper therapeutic doses, but hepatotoxicity can occur when misused or after an overdose. The principal toxic metabolite of acetaminophen is N-acetyl-p-benzoquinone imine (NAPQI). Toxicity should be considered in all suspicious cases because of the ubiquitous and initially asymptomatic nature of acetaminophen intoxication. Read More

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http://dx.doi.org/10.29271/jcpsp.2020.06.655DOI Listing
June 2020
0.318 Impact Factor

Monocyte-Derived Hepatocyte-Like Cell Test: A Novel Tool for in vitro Identification of Drug-Induced Liver Injury in Patients with Herbal or Dietary Supplements.

Digestion 2020 Jul 20:1-4. Epub 2020 Jul 20.

Department of Medicine II, Liver Centre Munich, University Hospital, Munich, Germany.

Background: Drug-induced liver injury caused by herbal and dietary supplements (HDS) has been an increasingly important phenomenon in recent years. Diagnosis is the major challenge. Definite causality assessment, especially in patients with concomitant prescription medicine or other potential causes of liver injury, can be impossible. Read More

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http://dx.doi.org/10.1159/000509391DOI Listing

Liver injury induced by paracetamol and challenges associated with intentional and unintentional use.

World J Hepatol 2020 Apr;12(4):125-136

Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States.

Drug induced liver injury (DILI) is a common cause of acute liver injury. Paracetamol, also known as acetaminophen, is a widely used anti-pyretic that has long been established to cause liver toxicity once above therapeutic levels. Hepatotoxicity from paracetamol overdose, whether intentional or non-intentional, is the most common cause of DILI in the United States and remains a global issue. Read More

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http://dx.doi.org/10.4254/wjh.v12.i4.125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336293PMC

Baicalin promotes liver regeneration after acetaminophen-induced liver injury by inducing NLRP3 inflammasome activation.

Free Radic Biol Med 2020 Jul 16. Epub 2020 Jul 16.

The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, 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:

Liver regeneration has become a new hotspot in the study of drug-induced liver injury (DILI). Baicalin has already been reported to alleviate acetaminophen (APAP)-induced acute liver injury in our previous study. This study aims to observe whether baicalin also promotes liver regeneration after APAP-induced liver injury and to elucidate its engaged mechanism. Read More

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http://dx.doi.org/10.1016/j.freeradbiomed.2020.05.012DOI Listing

Transient Hepatotoxicity Induced by Vinblastine in a Young Girl with Chiasmatic low Grade Glioma.

Curr Drug Saf 2020 Jul 18. Epub 2020 Jul 18.

Princess Máxima Center for Pediatric Oncology, PO box 113, 3720 AC Bilthoven. Netherlands.

Background: Vinblastine (VBL) is a cytostatic drug frequently applied in children with lymphoma and progressive low-grade glioma (LGG) in children, with hematotoxicity as main side effect.

Case Report: Here we present a 7-month-old girl with tumor progression of a LGG during standard chemotherapy with carboplatin and vincristine. Switch to VBL led to a 20-30-fold increase of transaminases (grade IV CTCAE 5. Read More

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http://dx.doi.org/10.2174/1574886315666200719013523DOI Listing

Bevacizumab Does Not Influence the Efficacy of Partial Splenic Embolization in the Management of Chemotherapy-Induced Hypersplenism.

Clin Colorectal Cancer 2020 Jun 12. Epub 2020 Jun 12.

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address:

Background: Antiangiogenics attenuate chemotherapy-related hepatotoxicity and portal hypertension. The potential impact of bevacizumab on the efficacy and safety of partial splenic embolization (PSE) in the management of chemotherapy-induced hypersplenism (CIH) has never been investigated.

Patients And Methods: We conducted a retrospective study with gastrointestinal cancer patients who have undergone PSE for the treatment of thrombocytopenia resulting from hypersplenism. Read More

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http://dx.doi.org/10.1016/j.clcc.2020.04.007DOI Listing

Hepatotoxicty of Agents Used in the Management of Inflammatory Bowel Disease: a 2020 Update.

Curr Gastroenterol Rep 2020 Jul 15;22(9):47. Epub 2020 Jul 15.

Department of Gastroenterology, MedStar Georgetown University Hospital, 3800 Reservoir Rd NW 2 Main, Washington, DC, 20007, USA.

Purpose Of Review: As treatment options for inflammatory bowel disease (IBD) continue to expand, the opportunity for hepatotoxicity remains a clinical concern. This review looks to update the current literature on drug-induced liver injury (DILI) and liver-related complications from current and emerging treatments for Crohn's disease (CD) and ulcerative colitis (UC).

Recent Findings: An extensive literature review on currently used medications to treat IBD and their liver-related side effects that includes mesalamine, thiopurines, certain antibiotics, methotrexate, anti-TNF agents including recently introduced biosimilars, anti-integrin therapy, anti-IL 12/IL 23 therapy, and small molecule JAK inhibitors. Read More

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http://dx.doi.org/10.1007/s11894-020-00781-3DOI Listing

Pre-treatment With PLGA/Silibinin Nanoparticles Mitigates Dacarbazine-Induced Hepatotoxicity.

Front Bioeng Biotechnol 2020 26;8:495. Epub 2020 Jun 26.

Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, South Dakota State University, Brookings, SD, United States.

Drug-induced hepatotoxicity is one of the major barriers limiting application of current pharmaceuticals as well as clinical translation of novel and perspective drugs. In this context, numerous hepatoprotective molecules have been proposed to prevent or mitigate drug-induced hepatotoxicity. To date, silibinin (SBN) is a one the most studied hepatoprotective plant-derived agents for prevention/alleviation of drug-induced liver injury. Read More

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http://dx.doi.org/10.3389/fbioe.2020.00495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332747PMC

Pyrazinamide enhances lipid peroxidation and antioxidant levels to induce liver injury in rat models through PI3k/Akt inhibition.

Toxicol Res (Camb) 2020 Jun 28;9(3):149-157. Epub 2020 Apr 28.

Department of Infectious Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.

Pyrazinamide (PZA) is an anti-tuberculosis drug known to causes liver injury. phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling protects against liver injury by promoting cellular antioxidant defenses and reducing intracellular reactive oxygen species (ROS) and lipid peroxidation. The regulatory mechanisms and functions of PI3K/Akt signaling during the hepatotoxicity of PZA are however not fully understood. Read More

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http://dx.doi.org/10.1093/toxres/tfaa015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329175PMC

LC-MS-Based Metabolomic Study of Oleanolic Acid-Induced Hepatotoxicity in Mice.

Front Pharmacol 2020 26;11:747. Epub 2020 May 26.

Key Laboratory of Basic Pharmacology of the Ministry of Education and Joint International Research Laboratory of Ethnomedicine of the Ministry of Education, Zunyi Medical University, Zunyi, China.

Oleanolic acid (OA), a natural triterpenoid, which has the development prospects in anti-tumor therapy is a widely used hepatoprotective drug in China. It has been reported that OA can cause liver toxicity after higher doses or longer-term use. Therefore, the study aims to explore the possible hepatotoxicity mechanism based on liver metabolic profiles. Read More

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http://dx.doi.org/10.3389/fphar.2020.00747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326119PMC

Malnutrition as an important risk factor for drug-induced liver injury in patients on anti-tubercular therapy: an experience from a tertiary care center in South India.

Drug Discov Ther 2020 ;14(3):135-138

Department of Infectious diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Karnataka, India.

Drug-induced liver injury (DILI) due to anti-tubercular treatment (ATT) leads to increased morbidity and mortality in patients with tuberculosis (TB). The aim of this study was to find the impact of malnutrition on the development of DILI. This was a prospective cohort study (September 2017 to August 2019) in which all newly diagnosed in-patients with tuberculosis above the age of 18 years were included. Read More

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http://dx.doi.org/10.5582/ddt.2020.03029DOI Listing

Lisinopril-Induced Liver Injury: An Unusual Presentation and Literature Review.

Eur J Case Rep Intern Med 2020 15;7(7):001600. Epub 2020 Apr 15.

Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.

Lisinopril is an angiotensin converting enzyme inhibitor (ACE-I) that has been on market for more than 25 years. ACE-I are usually well tolerated and rarely have serious or life-threatening side effects. We describe an unusual presentation of fulminant hepatic cholestasis probably secondary to lisinopril. Read More

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http://dx.doi.org/10.12890/2020_001600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350971PMC

[Research progress on laboratory diagnosis of drug-induced liver injury].

Authors:
H Li L Chen X X Zhang

Zhonghua Gan Zang Bing Za Zhi 2020 Jun;28(6):536-539

Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200025, China.

Drug-induced liver injury (DILI) is one of the common adverse drug reactions in the clinic and is also the main reason for the withdrawal of new drugs from the market. Although the overall incidence rate of DILI is not high; however, it can cause severe adverse outcome and even death, and has become the core cause of acute liver failure in Europe and the United States. In addition, DILI diagnosis is a puzzling problem for clinicians. Read More

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http://dx.doi.org/10.3760/cma.j.cn501113-20190313-00084DOI Listing

Toxicoproteomic Profiling of Transgenic Mice Treated with Rifampicin and Isoniazid.

Cells 2020 Jul 9;9(7). Epub 2020 Jul 9.

Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Tuberculosis is a global health threat that affects millions of people every year, and treatment-limiting toxicity remains a considerable source of treatment failure. Recent reports have characterized the nature of -mediated hepatotoxicity and the systemic toxicity of antitubercular drugs. The antitubercular drug isoniazid plays a role in such pathologic states as acute intermittent porphyria, anemia, hepatotoxicity, hypercoagulable states (deep vein thrombosis, pulmonary embolism, or ischemic stroke), pellagra (vitamin B deficiency), peripheral neuropathy, and vitamin B deficiency. Read More

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http://dx.doi.org/10.3390/cells9071654DOI Listing

Protection of CCl-induced hepatic and renal damage by linalool.

Drug Chem Toxicol 2020 Jul 13:1-9. Epub 2020 Jul 13.

Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.

The aim of the current study is to determine the protective and therapeutic effects of linalool against carbon tetrachloride (CCl)-induced hepatoxicity and nephrotoxicity. Six-week-old male Wistar rats were divided into five groups: Control group (a regular diet); CCl group (1 ml/kg dissolved in olive oil, intraperitoneally at 14th day); pretreatment group (25 mg/kg linalool daily + CCl 14thday); post-treatment group (25 mg/kg linalool 2, 6, 24, and 48 h after the injection of CCl at 14 day); and linalool group (25 mg/kg linalool daily, orally). All animals were sacrificed, tissue and blood samples were collected to analysis. Read More

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http://dx.doi.org/10.1080/01480545.2020.1792487DOI Listing

Acute liver injury following turmeric use in Tuscany: an analysis of the Italian Phytovigilance database and systematic review of case reports.

Br J Clin Pharmacol 2020 Jul 13. Epub 2020 Jul 13.

Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy.

Aims: Several cases of acute non-infectious cholestatic hepatitis recently appeared in Italy following consumption of Curcuma longa-containing dietary supplements. The aim of this research was to describe the Tuscan (Italy) cases of acute hepatitis and to compare them with similar cases of hepatotoxicity published in literature by performing a systematic review.

Methods: Records of Tuscan cases of acute hepatitis were obtained from the Italian Phytovigilance system. Read More

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http://dx.doi.org/10.1111/bcp.14460DOI Listing
July 2020
3.878 Impact Factor

Induction of Metabolic Zonation in Primary Hepatocytes Requires Both Near-Physiological Oxygen Concentration and Flux.

Front Bioeng Biotechnol 2020 3;8:524. Epub 2020 Jun 3.

Department of Chemical System Engineering, University of Tokyo, Tokyo, Japan.

Pre-clinical drug screening is an important step in assessing the metabolic effects and hepatic toxicity of new pharmaceutical compounds. However, due to the complexity of the liver microarchitecture, simplified models do not adequately reflect situations. Especially spatial heterogeneity, known as metabolic zonation, is often lost due to limitations introduced by typical culture conditions. Read More

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http://dx.doi.org/10.3389/fbioe.2020.00524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325921PMC

Mitochondrial Damage and Biogenesis in Acetaminophen-induced Liver Injury.

Liver Res 2019 Dec 1;3(3-4):150-156. Epub 2019 Nov 1.

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.

Liver injury and acute liver failure caused by acetaminophen (APAP) overdose is the clinically most important drug toxicity in western countries. Mechanistic investigations have revealed a central role of mitochondria in the pathophysiology. Excess formation of the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI) after an overdose leads to hepatic glutathione depletion, mitochondrial protein adducts formation and an initial oxidant stress, which triggers the activation of mitogen activated protein (MAP) kinase cascade ultimately leading to c-jun N-terminal kinase (JNK) phosphorylation. Read More

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http://dx.doi.org/10.1016/j.livres.2019.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351365PMC
December 2019

Autophagy alleviates amiodarone-induced hepatotoxicity.

Arch Toxicol 2020 Jul 10. Epub 2020 Jul 10.

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.

Amiodarone is a widely used antiarrhythmic drug that can cause the development of steatohepatitis as well as liver fibrosis and cirrhosis. The molecular mechanisms of amiodarone-mediated liver injury remain largely unknown. We therefore analyzed amiodarone-mediated hepatocellular injury in patients with chronic heart failure, in primary hepatocytes and HepG2 cells. Read More

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http://dx.doi.org/10.1007/s00204-020-02837-9DOI Listing

A sensitive upconverting nanoprobe based on signal amplification technology for real-time in situ monitoring of drug-induced liver injury.

Nanoscale 2020 Jul;12(28):15325-15335

State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing 210009, China.

Drug-induced liver injury (DILI) is increasingly recognized as one of the most challenging global health problems. Conventional in vitro detection methods not only lack specificity and sensitivity but also cannot achieve real-time, straightforward visualization of hepatotoxicity in vivo. Liver-specific miR122 has been observed to be a superior and sensitive biomarker for DILI diagnosis. Read More

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http://dx.doi.org/10.1039/d0nr01493aDOI Listing

An Evaluation of Postmarketing Reports of Serious Idiosyncratic Liver Injury Associated with Ulipristal Acetate for the Treatment of Uterine Fibroids.

Drug Saf 2020 Jul 9. Epub 2020 Jul 9.

Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.

Introduction: Ulipristal acetate (ulipristal) is a selective progesterone receptor modulator that has been marketed for daily use in Europe and Canada to reduce symptoms caused by uterine fibroids. Long-term use of some other members of this class of 19-norprogesterone-derived agents has been associated with idiosyncratic hepatotoxicity.

Objective: We analyzed postmarketing reports of suspected drug-induced liver injury associated with the daily use of 5 mg of ulipristal to treat symptoms of uterine fibroids. Read More

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http://dx.doi.org/10.1007/s40264-020-00960-1DOI Listing

Byakangelicin protects against carbon tetrachloride-induced liver injury and fibrosis in mice.

J Cell Mol Med 2020 Aug 9;24(15):8623-8635. Epub 2020 Jul 9.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.

Liver fibrosis is a disease caused by long-term damage that is related to a number of factors. The current research on the treatment of liver fibrosis mainly focuses on the activation of hepatic stellate cell, in addition to protecting liver cells. byakangelicin has certain anti-inflammatory ability, but its effect on liver fibrosis is unclear. Read More

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http://dx.doi.org/10.1111/jcmm.15493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412405PMC

Mechanistic insights into antiretroviral drug-induced liver injury.

Pharmacol Res Perspect 2020 Aug;8(4):e00598

Division of Chemical and System Biology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

All classes of antiretroviral therapy (ART) have been implicated to induce adverse drug reactions such drug-induced liver injury (DILI) and immune-mediated adverse reactions in Human Immunodeficiency Virus (HIV) infected individuals. Patients that develop adverse drug reactions tend to have prolonged stays in hospital and may require to change to alternative regimens if reactions persist upon rechallenge or if rechallenge is contraindicated due to severity of the adverse reaction. Diagnosis of DILI remains a huge obstacle that delays timely interventions, since it is still based largely on exclusion of other causes. Read More

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http://dx.doi.org/10.1002/prp2.598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344109PMC

Comparison of the Effects of Low-Molecular-Weight Heparin and Fondaparinux on Liver Function in Patients With Pulmonary Embolism.

J Clin Pharmacol 2020 Jul 8. Epub 2020 Jul 8.

Thrombosis Center, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Hepatotoxicity with low-molecular-weight heparin (LMWH) or fondaparinux is a relatively common adverse reaction. This study assessed the effects of LMWH and fondaparinux on liver function in patients with pulmonary embolism based on a retrospective cohort. As a result, a total of 463 patients with pulmonary embolism and treated with LMWH (enoxaparin sodium or nadroparin calcium) or fondaparinux sodium were included. Read More

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http://dx.doi.org/10.1002/jcph.1686DOI Listing

A retrospective case-controlled cohort study of inpatient drug induced liver injury: the RIDDLE study.

Transl Gastroenterol Hepatol 2020 5;5:33. Epub 2020 Jul 5.

Department of Gastroenterology, Eastern Health, Box Hill, Victoria, Australia.

Background: Identification of risk factors for drug-induced liver injury (DILI) has been hindered by the unpredictable incidence and idiosyncratic nature of DILI. The aim of this study was to identify characteristic host risk factors for DILI.

Methods: A retrospective cohort study was performed examining all patients admitted with a diagnosis of DILI over a 5. Read More

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http://dx.doi.org/10.21037/tgh.2019.10.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063506PMC

[Clinical application of the simultaneous detection of methotrexate and 7-hydroxymethotrexate in the delayed elimination for pediatric acute lymphoblastic leukemia].

Zhonghua Yi Xue Za Zhi 2020 Jul;100(25):1973-1978

Beijing Hospital, National Center of Gerontology, National Center for Clinical Laboratories, Graduate School of Peking Union Medical College, Beijing 100730, China.

To discuss the application value of the simultaneous determination of methotrexate (MTX) and 7-hydroxymethotrexate (7-OHMTX) in the delayed elimination of MTX for pediatric acute lymphoblastic leukemia (ALL). Cross sectional study. A total of 97 children who received 192 high-dose MTX treatments cycles in Lu Daopei Hospital from April to August 2019 were enrolled. Read More

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http://dx.doi.org/10.3760/cma.j.cn112137-20200424-01305DOI Listing

A novel pipeline of 2-(benzenesulfonamide)-N-(4-hydroxyphenyl) acetamide analgesics that lack hepatotoxicity and retain antipyresis.

Eur J Med Chem 2020 Jun 30;202:112600. Epub 2020 Jun 30.

Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, 70112, USA.

Although acetaminophen (ApAP) is one of the most commonly used medicines worldwide, hepatotoxicity is a risk with overdose or in patients with compromised liver function. ApAP overdose is the most common cause of acute fulminant hepatic failure. Oxidation of ApAP to N-acetyl-p-benzoquinone imine (NAPQI) is the mechanism for hepatotoxicity. Read More

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http://dx.doi.org/10.1016/j.ejmech.2020.112600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324353PMC

Quantifying drug-induced structural toxicity in hepatocytes and cardiomyocytes derived from hiPSCs using a deep learning method.

J Pharmacol Toxicol Methods 2020 Jul 3:106895. Epub 2020 Jul 3.

Division of Applied Regulatory Science, Office of Translational Science, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA. Electronic address:

Cardiac and hepatic toxicity result from induced disruption of the functioning of cardiomyocytes and hepatocytes, respectively, which is tightly related to the organization of their subcellular structures. Cellular structure can be analyzed from microscopy imaging data. However, subtle or complex structural changes that are not easily perceived may be missed by conventional image-analysis techniques. Read More

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http://dx.doi.org/10.1016/j.vascn.2020.106895DOI Listing

[Mechanism of psoralen in aggravating hepatotoxicity induced by CCl_4 by delaying liver regeneration].

Zhongguo Zhong Yao Za Zhi 2020 Jun;45(12):2916-2923

School of Traditional Chinese Medicine, Guangdong Pharmaceutical University Guangdong 510006, China Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University Nanjing 210009, China.

This study aimed to investigate whether psoralen can aggravate hepatotoxicity induced by carbon tetrachloride(CCl_4) by inducing hepatocyte cycle arrest and delaying liver regeneration. Female C57 BL/6 mice aged 6-8 weeks were randomly divided into control group, model group(CCl_4 group), combined group(CCl_4+PSO group) and psoralen group(PSO group). CCl_4 group and CCl_4+PSO group were given CCl_4 intraperitoneally at a dose of 100 μL·kg~(-1) once; olive oil of the same volume was given to control group and PSO group intraperitoneally; 12 h, 36 h and 60 h after CCl_4 injection, PSO group and CCl_4+PSO group were administrated with PSO intragastrically at a dose of 200 mg·kg~(-1); 0. Read More

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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200115.401DOI Listing

[Progress of research on effect and mechanism of Scutellariae Radix on preventing liver diseases].

Zhongguo Zhong Yao Za Zhi 2020 Jun;45(12):2808-2816

Jiangxi Key Laboratory of Natural Drug Research, College of Chemistry and Bioengineering,Yichun University Yichun 336000, China.

Scutellariae Radix is a kind of traditional Chinese medicine, which has the functions of heat-clearing and damp-drying, purging fire and detoxifying, hemostasis and miscarriage prevention. Modern pharmacological studies show that Scutellariae Radix has various effects, such as anti-oxidation, anti-inflammatory, liver protection and antiviral microorganisms. By searching the documents in the past ten years, the author has found that Scutellariae Radix and its active components play an important role in protecting the liver. Read More

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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200224.403DOI Listing

Seneciphylline, a main pyrrolizidine alkaloid in Gynura japonica, induces hepatotoxicity in mice and primary hepatocytes via activating mitochondria-mediated apoptosis.

J Appl Toxicol 2020 Jul 3. Epub 2020 Jul 3.

The MOE Key Laboratory for Standardization of 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, China.

Herbal drug-induced liver injury has been reported worldwide and gained global attention. Thousands of hepatic sinusoidal obstruction syndrome (HSOS) cases have been reported after consumption of herbal medicines and preparations containing pyrrolizidine alkaloids (PAs), which are natural phytotoxins globally distributed. And herbal medicines, such as Gynura japonica, are the current leading cause of PA-induced HSOS. Read More

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http://dx.doi.org/10.1002/jat.4004DOI Listing

Roles of diclofenac and its metabolites in immune activation associated with acute hepatotoxicity in TgCYP3A4/hPXR-humanized mice.

Int Immunopharmacol 2020 Jun 29;86:106723. Epub 2020 Jun 29.

School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China. Electronic address:

Diclofenac (DCF) is a widely used nonsteroidal anti-inflammatory drug, but it comes with a high risk of drug-induced liver injury (DILI). Despite the quinone-imine adduct pathways, the immunotoxicity is recently considered as another factor for DILI. However, such immune responses are still elusive. Read More

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http://dx.doi.org/10.1016/j.intimp.2020.106723DOI Listing

Nicotinamide attenuates cyclophosphamide-induced hepatotoxicity in SD rats by reducing oxidative stress and apoptosis.

J Biochem Mol Toxicol 2020 Jul 1:e22558. Epub 2020 Jul 1.

Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab, India.

Cyclophosphamide (CP) is a widely used anticancer and immunosuppressant drug. Nevertheless, clinical utilization of CP is limited due to considerable adverse effects and toxicities. Nicotinamide (NMD) is a micronutrient and the effect of NMD against CP-induced hepatotoxicity is yet unexplored. Read More

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http://dx.doi.org/10.1002/jbt.22558DOI Listing

Evaluation of Hepatoprotective Activity of the Crude Extract and Solvent Fractions of () Leaf Against CCl-Induced Hepatotoxicity in Mice.

J Exp Pharmacol 2020 9;12:137-150. Epub 2020 Jun 9.

Department of Pharmacy, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia.

Background: Liver is a vital organ that plays a major role in the elimination of xenobiotics from the body. Diseases that affect the liver become major health problems and challenge health-care professionals as well as the pharmaceutical industry. Since the conventional treatment of liver diseases is associated with a wide range of adverse effects, botanical agents are commonly used. Read More

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http://dx.doi.org/10.2147/JEP.S248677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294107PMC

Suppression of Cisplatin-Induced Hepatic Injury in Rats Through Alarmin High-Mobility Group Box-1 Pathway by : Theoretical and Experimental Study.

Drug Des Devel Ther 2020 11;14:2335-2353. Epub 2020 Jun 11.

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

Purpose: Drug-induced liver injury (DILI) is the most common cause of acute liver failure. The aim of this study was to investigate the molecular mechanisms by which mushroom (GLM) may ameliorate cisplatin (CP)-induced hepatotoxicity theoretically and experimentally.

Materials And Methods: Thirty-six male Sprague-Dawley (SD) rats were divided into six groups, two of them are normal and control groups. Read More

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http://dx.doi.org/10.2147/DDDT.S249093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296982PMC

Enoxaparin-Induced Liver Injury.

Case Rep Gastroenterol 2020 May-Aug;14(2):315-319. Epub 2020 Jun 10.

Department of Gastroenterology, Bronx Care Health System, Bronx, New York, USA.

Enoxaparin, a form of low-molecular-weight heparin, can cause a rare, underreported, and often reversible form of hepatocellular injury. This report describes a case of enoxaparin-induced hepatotoxicity in a 61-year-old male diagnosed with pulmonary embolism. Elevations of liver enzymes were noted within 1 week of starting the drug, followed by a dramatic improvement upon its discontinuation, with subsequent normalization in the following days. Read More

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http://dx.doi.org/10.1159/000508471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315174PMC