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hepatotoxic drugs

Yoon Hee Park, Soyeon Cho, Jeong Yee, Jae Youn Kim, Sandy Jeong Rhie, Hye Sun Gwak
Gefitinib is an oral tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) for non-small-cell lung cancer with EGFR mutations. Although a few studies have analyzed the causes of gefitinib-induced hepatotoxicity, research focusing on the time intervals before and after hepatotoxicity has yet to be reported. Therefore, this study investigated two types of factors: the time to reach gefitinib-induced hepatotoxicity and the time for recovery. From January 2013 to December 2014, a retrospective study was carried out on 473 non-small-cell lung cancer patients who were treated with gefitinib...
March 19, 2018: Anti-cancer Drugs
Javier Martínez-Casanova, Nuria Carballo, Sonia Luque, Luisa Sorli, Santiago Grau
Azole antifungals have frequently been linked to the presence of hepatotoxicity, but there is scarce information on cross-toxicity between these drugs or on the possibility of using some of them when this type of toxicity occurs. We report the case of a 64-year-old man with invasive aspergillosis (IA) leading to spondylodiscitis with neurological involvement. Early management included intravenous (iv) voriconazole, which had to be interrupted after 1 week due to liver damage. Therapeutic drug monitoring (TDM) of voriconazole showed that the plasma concentration was within the therapeutic range...
2018: Infection and Drug Resistance
Xianxun Shi, Huiyuan Bai, Ming Zhao, Xiaorong Li, Xianchao Sun, Hongbo Jiang, Ailing Fu
Drug-induced liver injury shares a common feature of mitochondrial dysfunction. Mitochondrial therapy (mitotherapy), which replaces malfunctional mitochondria with functional exogenous mitochondria, may be a fundamental approach for treating drug-mediated hepatotoxicity. Here, we suggested that mitochondria isolated from human hepatoma cell could be used to treat acetaminophen (APAP)-induced liver injury in mice. When the mitochondria were added into the cell media, they could enter primarily cultured mouse hepatocyte...
March 2, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Marco Fiore, Sebastiano Leone, Alberto Enrico Maraolo, Emilio Berti, Giovanni Damiani
Psoriasis is a chronic inflammatory disease of the skin affecting approximately 2% of the world's population. Systemic treatments, including methotrexate and cyclosporin, are associated with potential hepatotoxicity, due to either direct liver damage or immunosuppression or both immunomediated and a direct liver injury; therefore, treatment of patients with psoriasis poses a therapeutic challenge. The aim of this minireview is to help clinicians in the management of psoriatic patients who develop signs of liver dysfunction...
2018: BioMed Research International
Nora Freyer, Selina Greuel, Fanny Knöspel, Florian Gerstmann, Lisa Storch, Georg Damm, Daniel Seehofer, Jennifer Foster Harris, Rashi Iyer, Frank Schubert, Katrin Zeilinger
The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP ( p < 0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP ( p < 0...
March 15, 2018: Bioengineering
Xue-Yang Jiang, Ting-Kai Chen, Jun-Ting Zhou, Si-Yu He, Hong-Yu Yang, Yao Chen, Wei Qu, Feng Feng, Hao-Peng Sun
Designing multitarget-directed ligands (MTDLs) is considered to be a promising approach to address complex and multifactorial maladies such as Alzheimer's disease (AD). The concurrent inhibition of the two crucial AD targets, glycogen synthase kinase-3β (GSK-3β) and human acetylcholinesterase ( h AChE), might represent a breakthrough in the quest for clinical efficacy. Thus, a novel family of GSK-3β/AChE dual-target inhibitors was designed and synthesized. Among these hybrids, 2f showed the most promising profile as a nanomolar inhibitor on both h AChE (IC50 = 6...
March 8, 2018: ACS Medicinal Chemistry Letters
Wolfgang Miehsler, Clemens Dejaco, Hans-Peter Gröchenig, Harry Fuchssteiner, Christoph Högenauer, Lili Kazemi-Shirazi, Harald Maier, Andreas Mayer, Alexander Moschen, Walter Reinisch, Wolfgang Petritsch, Reingard Platzer, Pius Steiner, Herbert Tilg, Harald Vogelsang, Heimo Wenzl, Gottfried Novacek
Anti-TNFα-antibodies have revolutionized the therapy of inflammatory bowel diseases and other immune-mediated inflammatory diseases. Due to the increasing application of these substances, the Working Group of Inflammatory Bowel Diseases of the Austrian Association of Gastroenterology and Hepatology intended to update their consensus report on the safe use of Infliximab (published in 2010) and to enlarge its scope to cover all anti-TNFα-antibodies. The present consensus report summarizes the current evidence on the safe use of anti-TNFα-antibodies and covers the following topics: general risk of infection, bacterial infections (i...
March 2018: Zeitschrift Für Gastroenterologie
Peng Sun, Jing-Jie Zhu, Ting Wang, Qi Huang, Yu-Ren Zhou, Bang-Wei Yu, Hua-Liang Jiang, He-Yao Wang
As a widely used anti-gout drug, benzbromarone has been found to induce hepatic toxicity in patients during clinical treatment. Previous studies have reported that benzbromarone is metabolized via cytochrome P450, thus causing mitochondrial toxicity in hepatocytes. In this study, we found that benzbromarone significantly aggravated hepatic steatosis in both obese db/db mice and high fat diet (HFD)-induced obese (DIO) mouse models. However, benzbromarone had less effect on the liver of lean mice. It was found that the expression of mRNAs encoding lipid metabolism and some liver-specific genes were obviously disturbed in benzbromarone-treated DIO mice compared to the control group...
March 8, 2018: Biochimica et Biophysica Acta
Michael Schloss, Daniel Becak, Sebastian T Tosto, Arash Velayati
BACKGROUND Levofloxacin covers a broad spectrum of pathogens and is readily prescribed by clinicians. Hepatotoxicity is a known but unusual complication of levofloxacin use. Here, we present a case of severe transaminitis caused by levofloxacin. CASE REPORT A young man in his thirties with a history of asthma, chronic alcoholism, methamphetamine intravenous drug abuse (IVDA), and non-compliant insulin-dependent diabetes mellitus (IDDM) presented to an emergency department with suicidal ideation. Vital signs were stable and the patient was noted to have cellulitis of the right forearm, for which cultures were drawn, and he received IV clindamycin...
March 10, 2018: American Journal of Case Reports
Mark W Niedfeldt
Anabolic steroids are synthetic derivatives of testosterone shown to increase muscle size and strength. Chemical substitutions on the testosterone molecule cause increased potency and duration of action. The 17-α-alkylation modification allows steroids to be taken orally, but the slower clearance in the liver makes them more hepatotoxic. The frequency and severity of side effects depends on several factors including the formulation of the drug, route of administration, dosage, duration of use, and individual sensitivity and response...
March 2018: Current Sports Medicine Reports
María Elena Iezzi, Lucía Policastro, Santiago Werbajh, Osvaldo Podhajcer, Gabriela Alicia Canziani
Monoclonal antibodies and their fragments have significantly changed the outcome of cancer in the clinic, effectively inhibiting tumor cell proliferation, triggering antibody-dependent immune effector cell activation and complement mediated cell death. Along with a continued expansion in number, diversity, and complexity of validated tumor targets there is an increasing focus on engineering recombinant antibody fragments for lead development. Single-domain antibodies (sdAbs), in particular those engineered from the variable heavy-chain fragment (VHH gene) found in Camelidae heavy-chain antibodies (or IgG2 and IgG3), are the smallest fragments that retain the full antigen-binding capacity of the antibody with advantageous properties as drugs...
2018: Frontiers in Immunology
Antonios Douros, Laurent Azoulay, Hui Yin, Samy Suissa, Christel Renoux
BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are relatively new drugs used for stroke prevention in nonvalvular atrial fibrillation (NVAF). However, there are concerns that their use may be associated with hepatotoxic effects. OBJECTIVES: The purpose of this study was to determine whether the use of NOACs is associated with an increased risk of serious liver injury compared with the use of vitamin K antagonists (VKAs) in NVAF patients with and without prior liver disease...
March 13, 2018: Journal of the American College of Cardiology
Alamgeer, Zain Nasir, Muhammad Naeem Qaisar, Ambreen Malik Uttra, Haseeb Ahsan, Kifayat Ullah Khan, Ikram Ullah Khan, Muhamamd Saleem, Khadijai, Hira Asif, Amber Sharif, Waqas Younis, Huma Naz
Hepatic diseases are becoming common day by day and pose serious health threats to the life of humans. In order to treat these diseases, the attention of man is diverting towards herbal drugs, which are much safer and cost effective than synthetic drugs. The aim of present study was to investigate hepatoprotective activity of methanolic extract of Melilomus officinalis against paracetamol and carbon tetrachloride induced hepatic damage. Melilotus officinalis at selected oral doses of 50 mg/kg and 100 mg/kg showed significant hepatoprotective effects by decreasing the levels of serum marker enzymes such as total bilirubin, SGOT, SGPT, ALP, albumin and total protein, when compared with standard drug (silymarin) and negative control...
May 2017: Acta Poloniae Pharmaceutica
Bing Liu, Maoxi Yuan, Yi Sun, Ziming Cheng, Zaiyong Zhang, Shizheng Hou, Xiangdong Wang, Jingfeng Liu
Background: Two anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (-TKIs) have been approved for the treatment of patients with ALK-rearranged (ALK-positive) advanced non-small cell lung cancer (NSCLC). Severe hepatotoxicity has been observed in several clinical studies. We aim to assess the incidence and risk of liver toxicity with these drugs by a systematic review and meta-analysis of clinical trials. Materials and Methods: The databases of PubMed, Web of Science and abstracts presented at oncology conferences' proceedings were searched for relevant studies from January 2000 to January 2017...
February 6, 2018: Oncotarget
Clement Bresteau, Sophie Prevot, Gabriel Perlemuter, Cosmin Voican
Drug-induced liver injury is the fourth most common cause of liver disease in industrialised countries. Methylprednisolone is often considered to be a treatment with a low hepatotoxicity. We report a case of methylprednisolone-induced liver injury in a 35-year-old woman. She was admitted to our department for acute liver injury 2 months after a treatment with high dose of methylprednisolone (1 g/day) for a multiple sclerosis relapse. No other cause of liver injury could be found (screening for hepatotropic viruses, autoimmune antibodies, ceruloplasmin, abdominal ultrasonography and liver biopsy)...
March 5, 2018: BMJ Case Reports
Pranav Joshi, Akshata Datar, Kyeong-Nam Yu, Soo-Yeon Kang, Moo-Yeal Lee
The majority of high-content imaging (HCI) assays have been performed on two-dimensional (2D) cell monolayers for its convenience and throughput. However, 2D-cultured cell models often do not represent the in vivo characteristics accurately and therefore reduce the predictability of drug toxicity/efficacy in vivo. Recently, three-dimensional (3D) cell-based HCI assays have been demonstrated to improve predictability, but its use is limited due to difficulty in maneuverability and low throughput in cell imaging...
February 28, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Elizabeth E Krans, Scott D Rothenberger, Penelope K Morrison, Seo Young Park, Leah C Klocke, Mary J Turocy, Susan Zickmund
Objectives To evaluate Hepatitis C virus (HCV) knowledge and awareness among pregnant women with opioid use disorder (OUD). Methods From May through November 2015, a one-time survey was distributed to a convenience sample of pregnant women with OUD to assess their knowledge and awareness of (a) risk factors for HCV infection, (b) HCV transmission prevention strategies, (c) hepatotoxic risk reduction and (d) perinatal transmission and neonatal implications of HCV infection. Chi square and Fisher's exact tests were used to compare demographic characteristics and HCV knowledge between participants who were HCV positive and negative...
March 3, 2018: Maternal and Child Health Journal
Andreas Dieckmann, Peter H Hagedorn, Yvonne Burki, Christine Brügmann, Marco Berrera, Martin Ebeling, Thomas Singer, Franz Schuler
The successful development of high-affinity gapmer antisense oligonucleotide (ASO) therapeutics containing locked nucleic acid (LNA) or constrained ethyl (cEt) substitutions has been hampered by the risk of hepatotoxicity. Here, we present an in vitro approach using transfected mouse fibroblasts to predict the potential hepatic liabilities of LNA-modified ASOs (LNA-ASOs), validated by assessing 236 different LNA-ASOs with known hepatotoxic potential. This in vitro assay accurately reflects in vivo findings and relates hepatotoxicity to RNase H1 activity, off-target RNA downregulation, and LNA-ASO-binding affinity...
March 2, 2018: Molecular Therapy. Nucleic Acids
Ajeet Kumar Verma, Arti Yadav, Sarvendra Vikram Singh, Pratibha Mishra, Srikanta Kumar Rath
AIMS: Long-term treatment of Isoniazid (INH) in tuberculosis (TB) patients can lead to anti-tuberculosis drug-induced hepatotoxicity. To understand the mechanism of hepatotoxicity, an attempt has been made to elucidate the role of Nrf2, a transcription factor induced by oxidative stress, in INH induced apoptosis liver cancer cell lines. MATERIALS AND METHODS: Cytotoxicity was evaluated by MTT assay. Apoptosis and reactive oxygen species (ROS) generation was performed by flow cytometry...
February 27, 2018: Life Sciences
Isha Ranadive, Sonam Patel, Abhilasha Mhaske, Gowri Kumari Uggini, Isha Desai, Suresh Balakrishnan
Currently, scientists show keen interest in the drugs that inhibit multiple kinases, LDN193189, being an example. It combats certain cancers in vitro as well as in vivo, making it a prerequisite for researchers to study the toxic potential of this drug in animal models. As most of the drugs metabolized by liver cause hepatic injury, LDN193189-induced hepatotoxicity was examined using a teleost fish, Poecilia latipinna. As a prelude, calculation of LD50 showed a value of 95.22 mg/kg body weight and three doses were decided based on it for further evaluations...
March 2, 2018: Drug and Chemical Toxicology
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