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drug-induced liver injury

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https://www.readbyqxmd.com/read/28748913/d-chiro-inositol-effectively-attenuates-cholestasis-in-bile-duct-ligated-rats-by-improving-bile-acid-secretion-and-attenuating-oxidative-stress
#1
Shuang-Shuang Zhao, Na-Ren Li, Wu-Li Zhao, Hong Liu, Mao-Xu Ge, Yi-Xuan Zhang, Long-Yin Zhao, Xue-Fu You, Hong-Wei He, Rong-Guang Shao
Cholestatic liver diseases are important causes of liver cirrhosis and liver transplantation, but few drugs are available for treatment. D-chiro-inositol (DCI), an isomer of inositol found in many Leguminosae plants and in animal viscera, is used clinically for the treatment of polycystic ovary syndrome (PCOS) and diabetes mellitus. In this study, we investigated whether DCI exerted an anti-cholestatic effect and its underlying mechanisms. A cholestatic rat model was established via bile duct ligation (BDL)...
July 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28748471/evaluation-of-mitochondrial-respiration-in-cultured-rat-hepatocytes
#2
Jean-Pierre Marchandeau, Gilles Labbe
Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver injury and other serious side effects, such as lactic acidosis and rhabdomyolysis, in some patients. Several in vitro and in vivo investigations can be performed in order to determine if drugs can disturb mitochondrial fatty acid oxidation (FAO) and the oxidative phosphorylation (OXPHOS) process, deplete hepatic mitochondrial DNA (mtDNA), or trigger the opening of the mitochondrial permeability transition pore (MPT). Among these investigations, mitochondrial respiration is a relatively easy test to measure the potential toxicity of a drug...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28748198/abacavir-dolutegravir-lamivudine-triumeq-induced-liver-toxicity-in-a-human-immunodeficiency-virus-infected-patient
#3
Erin S Christensen, Rupali Jain, Alison C Roxby
Drug-induced liver injury related to Triumeq (abacavir/lamivudine/dolutegravir) has not been reported in clinical trials. We report a case of hepatotoxicity related to Triumeq exposure in a human immunodeficiency virus-infected patient. Clinicians should remain aware of the risk for acute and late-onset hepatitis with these agents. Close monitoring is recommended.
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28747986/comparison-of-therapeutic-responses-to-an-anticancer-drug-in-three-stocks-of-icr-mice-derived-from-three-different-sources
#4
Ji Eun Sung, Ji Eun Kim, Hyun Ah Lee, Woo Bin Yun, Jun Young Choi, Mi Rim Lee, Jin Ju Park, Hye Ryeong Kim, Bo Ram Song, Young Suk Jung, Kil Soo Kim, Dae Youn Hwang
Korl:ICR mice, established by the Korean National Institute of Food and Drug Safety Evaluation (NIFDS), are characterized based on their genetic variation, response to gastric injury, and response to constipation inducers. To compare the inhibitory responses of ICR stocks obtained from three different sources to the anticancer drug cisplatin (Cis), alterations in tumor volume, histopathological structure, and toxicity were examined in Sarcoma 180 tumor-bearing Korl:ICR, A:ICR (USA source), and B:ICR (Japan source) mice treated with low and high concentrations of Cis (L-Cis and H-Cis, respectively)...
June 2017: Laboratory Animal Research
https://www.readbyqxmd.com/read/28743512/inferring-transcription-factor-activity-from-microarray-data-reveals-novel-targets-for-toxicological-investigations
#5
T M Souza, T van den Beucken, J C S Kleinjans, D G J Jennen
Transcription factors (TFs) are important modulators of the inducible portion of the transcriptome, and therefore relevant in the context of exposure to exogenous compounds. Current approaches to predict the activity of TFs in biological systems are usually restricted to a few entities at a time due to low-throughput techniques targeting a limited fraction of annotated human TFs. Therefore, high-throughput alternatives may help to identify new targets of mechanistic and predictive value in toxicological investigations...
July 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28743082/characterization-and-evaluation-of-nanoencapsulated-diethylcarbamazine-in-model-of-acute-hepatic-inflammation
#6
Gabriel Barros Rodrigues, Elquio Eleamen Oliveira, Francisco Jaime Bezerra Mendonça Junior, Laise Aline Martins Dos Santos, Wilma Helena de Oliveira, Maria Eduarda Rocha de França, Deniele Bezerra Lós, Brennda Martins Gabínio, Fábia Cristiane Melo Leite de Lira, Christina Alves Peixoto
Previous studies from our laboratory have demonstrated that Diethylcarbamazine (DEC) is a potent anti-inflammatory drug. The aim of the present study was to characterize the nanoencapsulation of DEC and to evaluate its effectiveness in a model of inflammation for the first time. C57BL/6 mice were divided into six groups: 1) Control; 2) Carbon tetrachloride (CCl4); 3) DEC 25mg/kg+CCl4; 4) DEC 50mg/kg+CCl4; 5) DEC-NANO 05mg/kg+CCl4 and 6) DEC-NANO 12.5mg/kg+CCl4. Liver fragments were stained with hematoxylin-eosin, and processed for Western blot, ELISA and immunohistochemistry...
July 22, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28733206/omics-based-identification-of-the-combined-effects-of-idiosyncratic-drugs-and-inflammatory-cytokines-on-the-development-of-drug-induced-liver-injury
#7
J Jiang, K Mathijs, L Timmermans, S M Claessen, A Hecka, J Weusten, R Peters, J H van Delft, J C S Kleinjans, D G J Jennen, T M de Kok
The mechanisms of idiosyncratic drug-induced hepatotoxicity remain largely unclear. It has demonstrated that the drug idiosyncrasy is potentiated in the context of inflammation and intracellular ceramides may play a role in this process. To study the mechanisms, HepG2 cells were co-treated with high and low doses of three idiosyncratic (I) and three non-idiosyncratic (N) compounds, with (I+ and N+) or without (I- and N-) a cytokine mix. Microarray, lipidomics and flow cytometry were performed to investigate the genome-wide expression patterns, the intracellular ceramide levels and the induction of apoptosis...
July 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28730164/effect-of-bicyclol-tablets-on-drug-induced-liver-injuries-after-kidney-transplantation
#8
Wenjun Shang, Yonghua Feng, Jinfeng Li, Xinzhou Wang, Hongchang Xie, Guiwen Feng
Liver injury is one of the most common complications in patients after kidney transplantation. Bicyclol tablets possess obvious anti-inflammatory and liver-protective functions. This study aimed to explore the clinical effect of preventive application of Bicyclol on drug induced liver injuries at an early stage after kidney transplantation. A total of 1600 patients who accepted kidney transplantations at our hospital from January 2009 to May 2015 were enrolled in this study, and divided into the prevention group (Bicyclol) and the control group (no hepatic protectors) based on whether or not hepatic protectors were regularly administered after the operation...
2017: Open Medicine (Warsaw, Poland)
https://www.readbyqxmd.com/read/28729056/discovery-and-structure-activity-relationship-of-auriculatone-a-potent-hepatoprotective-agent-against-acetaminophen-induced-liver-injury
#9
Meng Zhou, Min Wang, Rui-Feng Zhong, Xiang-Ming Liao, Lian-Li Deng, Guo-Bo Xu, Xun He, Jing Li, Yong-Jun Li, Ting Liu, Yong-Lin Wang, Shang-Gao Liao
Acetaminophen (APAP, paracetamol) overdose has been the most frequent cause of drug-induced liver failure. APAP-induced liver toxicity can be fatal in many cases even with treatment of the clinically used N-acetylcysteine (NAC), and the need for novel therapeutic agents is apparent. Through evaluating the hepatoprotective effects of the co-occurring substances present in oleanolic acid tablets which have been used in China for decades as an adjuvant therapy for acute and chronic hepatitis, auriculatone was found to protect HL-7702 cells from APAP-induced liver injury comparable to NAC at the concentration of 10μM...
July 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28722244/risk-of-liver-decompensation-with-cumulative-use-of-mitochondrial-toxic-nucleoside-analogues-in-hiv-hepatitis-c-virus-coinfection
#10
Vincent Lo Re Rd, Bret Zeldow, Michael J Kallan, Janet P Tate, Dena M Carbonari, Sean Hennessy, Jay R Kostman, Joseph K Lim, Matthew Bidwell Goetz, Robert Gross, Amy C Justice, Jason A Roy
PURPOSE: Among patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death. METHODS: We conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients...
July 19, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28717830/a-review-of-drug-induced-liver-injury-databases
#11
REVIEW
Guangwen Luo, Yiting Shen, Lizhu Yang, Aiping Lu, Zheng Xiang
Drug-induced liver injuries have been a major focus of current research in drug development, and are also one of the major reasons for the failure and withdrawal of drugs in development. Drug-induced liver injuries have been systematically recorded in many public databases, which have become valuable resources in this field. In this study, we provide an overview of these databases, including the liver injury-specific databases LiverTox, LTKB, Open TG-GATEs, LTMap and Hepatox, and the general databases, T3DB, DrugBank, DITOP, DART, CTD and HSDB...
July 17, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28717109/utility-of-human-hepatocyte-spheroids-without-feeder-cells-for-evaluation-of-hepatotoxicity
#12
Takuo Ogihara, Hiroshi Arakawa, Tomoko Jomura, Yoko Idota, Satoshi Koyama, Kentaro Yano, Hajime Kojima
We investigated the utility of three-dimensionally cultured hepatocytes (spheroids) without feeder cells (Sph(f-)) for the prediction of drug-induced liver injury (DILI) in humans. Sph(f-) and spheroids cultured on feeder cells (Sph(f+)) were exposed to the hepatotoxic drugs flutamide, diclofenac, isoniazid and chlorpromazine at various concentrations for 14 days, and albumin secretion and cumulative leakages of toxicity marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GTP), were measured...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28717101/mechanism-based-risk-assessment-strategy-for-drug-induced-cholestasis-using-the-transcriptional-benchmark-dose-derived-by-toxicogenomics
#13
Taisuke Kawamoto, Yuichi Ito, Osamu Morita, Hiroshi Honda
Cholestasis is one of the major causes of drug-induced liver injury (DILI), which can result in withdrawal of approved drugs from the market. Early identification of cholestatic drugs is difficult due to the complex mechanisms involved. In order to develop a strategy for mechanism-based risk assessment of cholestatic drugs, we analyzed gene expression data obtained from the livers of rats that had been orally administered with 12 known cholestatic compounds repeatedly for 28 days at three dose levels. Qualitative analyses were performed using two statistical approaches (hierarchical clustering and principle component analysis), in addition to pathway analysis...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28713494/caspase-3-role-and-immunohistochemical-expression-in-assessment-of-apoptosis-as-a-feature-of-h1n1-vaccine-caused-drug-induced-liver-injury-dili
#14
Abir Khalil Mohamed, Mona Magdy
BACKGROUND: Drug-Induced Liver Injury (DILI) changes, occur post exposure to natural or chemical compounds including apoptosis. AIM: To assess the H1N1 vaccine-caused DILI by histochemical and immunohistochemical methods. METHODS: This 2014's experimental study was conducted on 70 albino rats. They were given Arepanrix(TM) H1N1 vaccine and were divided into 7 groups; 10 mice each, as control (non-vaccinated), vac2 and vac4 injected with 1(st) and 2(nd) doses of vaccine (suspension only) and euthanized after 3 weeks each, vac5 euthanized 6 weeks after 2(nd) dose, mix2 and mix4 injected with 1(st) and 2(nd) doses of vaccine (mixture of suspension and adjuvant) and euthanized after 3 weeks each, mix5 and euthanized 6 weeks after 2(nd) dose...
May 2017: Electronic Physician
https://www.readbyqxmd.com/read/28712788/antimalarial-agent-artesunate-protects-concanavalin-a-induced-autoimmune-hepatitis-in-mice-by-inhibiting-inflammatory-responses
#15
Xin Zhao, MingJiang Liu, JinGui Li, ShaoJie Yin, YangYang Wu, AnYuan Wang
The anti-malarial drug artesunate (ARS) has been shown to possess anti-inflammatory activity. Its effect on autoimmune hepatitis remains unclear. Concanavalin A (Con A)-induced hepatitis was used in this study to reveal the potential action of ARS and the related mechanism. Mice were pretreated with ARS followed by Con A challenge. Con A caused obvious hepatic injury with higher levels of liver enzymes, elevated pro-inflammatory cytokines and activation of nuclear factor-κB (NF-κB) and mitogen activated protein kinase (MAPK) signaling pathways...
July 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28712691/biliary-bile-acids-in-hepatobiliary-injury-what-is-the-link
#16
REVIEW
Peter Fickert, Martin Wagner
The main trigger for liver injury in acquired cholestatic liver disease remains unclear. However, the accumulation of bile acids (BAs) undoubtedly plays a role. Recent progress in deciphering the pathomechanisms of inborn cholestatic liver diseases, decoding mechanisms of BA-induced cell death, and generating modern BA-derived drugs has improved the understanding of the regulation of BA synthesis and transport. Now is the appropriate time to reassess current knowledge about the specific role of BAs in hepatobiliary injury...
July 13, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28702139/ramipril-associated-cholestasis-in-the-setting-of-recurrent-drug-induced-liver-injury
#17
David Forner, Tasha Kulai, Thomas Arnason, Steven E Gruchy, Magnus MacLeod
Aim: Angiotensin-converting enzyme inhibitors (ACEIs) are commonly used to treat hypertension. Although generally well tolerated, the adverse effects of ACEIs include hypotension, cough, acute kidney injury and hyperkalemia. Rare reports of ACEI-induced hepatotoxicity have been described, most notably a cholestatic pattern of injury related to captopril. A 67-year-old male presented to the emergency department with a three-week history of jaundice, pruritis and weakness. Eight weeks before, he began taking ramipril and clopidogrel...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28694671/substantial-hepatic-necrosis-is-prognostic-in-fulminant-liver-failure
#18
Paul Ndekwe, Marwan S Ghabril, Yong Zang, Steven A Mann, Oscar W Cummings, Jingmei Lin
AIM: To evaluate if any association existed between the extent of hepatic necrosis in initial liver biopsies and patient survival. METHODS: Thirty-seven patients with fulminant liver failure, whose liver biopsy exhibited substantial necrosis, were identified and included in the study. The histological and clinical data was then analyzed in order to assess the relationship between the extent of necrosis and patient survival, with and without liver transplantation...
June 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28691103/role-of-nonalcoholic-fatty-liver-disease-as-risk-factor-for-drug-induced-hepatotoxicity
#19
Julie Massart, Karima Begriche, Caroline Moreau, Bernard Fromenty
BACKGROUND: Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. AIM: The main objective of the present review was to collect the available information regarding the role of NAFLD as risk factor for drug-induced hepatotoxicity...
February 2017: Journal of Clinical and Translational Research
https://www.readbyqxmd.com/read/28690936/a-case-of-imatinib-induced-hepatitis
#20
Osman Bhatty, Mohammad Selim, Thamer Kassim, Lakshmi Chintalacheruvu, Manuel Urra, Sonia Shah, Joseph Haggerty, John Gross, Aravdeep Jhand, Gene Pershwitz, Jaya Gupta
A 71-year-old female with a past medical history of Philadelphia chromosome-positive chronic myelogenous leukemia on imatinib therapy, Sjogren's syndrome, and hypothyroidism presents with acute hepatitis. After a comprehensive workup ruling out viral, infectious and metabolic etiologies imatinib is stopped which results in immediate improvement. The biopsy is consistent with drug-induced liver damage; the patient is started on oral prednisone and discharged. Unfortunately, our patient's liver function does not improve over the course of the next week and she is readmitted for hepatic and renal failure...
June 1, 2017: Curēus
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