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drug-induced liver injury

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https://www.readbyqxmd.com/read/29148292/cholestatic-liver-injury-as-a-side-effect-of-dabigatran-and-the-use-of-coagulation-tests-in-dabigatran-intoxication-and-after-reversal-by-idarucizumab-in-bleeding-and-sepsis
#1
Willemijn J Comuth, Anne-Mette Haase, Linda Ø Henriksen, Jerzy Malczynski, Daan van de Kerkhof, Anna-Marie B Münster
Idarucizumab, an antidote specific for dabigatran, became available recently. Dabigatran is not associated with increased risk of hepatotoxicity in comparison with warfarin, but it is seen as a rare side-effect. Cases of cholestatic liver injury due to dabigatran have not been reported previously. We present a case of severe gastro-intestinal bleeding with underlying dabigatran intoxication in a patient with renal failure and the effect of reversal of dabigatran using idaruzicumab on coagulation assays. International normalized ratio (INR) and activated partial thromboplastin time (APTT) results were elevated in a setting of sepsis, possibly due to liver failure...
November 17, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/29147529/ratiometric-photoacoustic-imaging-of-endoplasmic-reticulum-polarity-in-injured-liver-tissues-of-diabetic-mice
#2
Haibin Xiao, Chuanchen Wu, Ping Li, Wen Gao, Wen Zhang, Wei Zhang, Lili Tong, Bo Tang
As one of the complications of diabetes, liver injury results in significant hazards. Therefore, accurately diagnosing diabetes-induced liver injury beforehand is crucial for the warning and treatment of hepatic diseases. Diabetes-induced liver injury can cause changes in the microstructure and morphology of liver tissue, leading to changes in the hydrophilic and hydrophobic domains in the endoplasmic reticulum (ER), which is closely associated with changes in cellular ER polarity. So, differences in the ER polarity can indicate the degree of diabetes-induced liver injury...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29146462/individual-serum-bile-acid-profiling-in-rats-aids-in-human-risk-assessment-of-drug-induced-liver-injury-due-to-bsep-inhibition
#3
Steven Cepa, David Potter, Lisa Wong, Leah Schutt, Jacqueline Tarrant, Jodie Pang, Xiaolin Zhang, Roxanne Andaya, Laurent Salphati, Yingqing Ran, Le An, Ryan Morgan, Jonathan Maher
Drug-induced liver injury (DILI) has been the most frequent cause of post-marketing drug withdrawals in the last 50years. The multifactorial nature of events that precede severe liver injury in human patients is difficult to model in rodents due to a variety of confounding or contributing factors that include disease state, concurrent medications, and translational species differences. In retrospective analyses, a consistent risk factor for DILI has been the inhibition of the Bile Salt Export Pump (BSEP). One compound known for potent BSEP inhibition and severe DILI is troglitazone...
November 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29145837/molecular-network-based-analysis-of-the-mechanism-of-liver-injury-induced-by-volatile-oils-from-artemisiae-argyi-folium
#4
Hongjie Liu, Sha Zhan, Yan Zhang, Yan Ma, Liang Chen, Lingxiu Chen, Hanqiu Dong, Min Ma, Zhe Zhang
BACKGROUND: Volatile oils from Artemisiae argyi folium (VOAAF) is reported with hepatotoxicity, but the underlying mechanism is still unclear. METHODS: In the present study this molecular mechanism was explored with the Ingenuity Pathway Analysis (IPA). The chemical components of the VOAAF were searched in the database, and their target proteins were all identified in the PubChem, while drug-induced liver injury (DILI) genes were searched in the PubMed gene databases...
November 16, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29138819/beneficial-effect-of-resveratrol-on-%C3%AE-%C3%A2-naphthyl-isothiocyanate%C3%A2-induced-cholestasis-via-regulation-of-the-fxr-pathway
#5
Lili Ding, Binfeng Zhang, Jinmei Li, Li Yang, Zhengtao Wang
Cholestasis is defined as a functional impairment of bile secretion which results in the accumulation of bile acids (BAs) and other toxic molecules in the blood and liver, however, there are very few effective therapies for cholestasis. The farnesoid X receptor (FXR), as a nuclear receptor for BAs, is important in the regulation of BA levels in enterohepatic circulation. It has previously been demonstrated that activation of the FXR pathway may be a useful strategy with which to treat cholestasis. Resveratrol, one of the important ingredients from grape skins and Chinese medicine Polygonum cuspidatum, resulted in FXR‑activated effects in vitro and exhibited a protective effect against α‑naphthylisothiocyanate (ANIT)‑induced cholestasis through FXR regulation in vivo...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29136767/the-exposure-effect-toxicity-correlation-of-docetaxel-and-magnesium-isoglycyrrhizinate-in-non-small-cell-lung-tumor-bearing-mice
#6
Peijin Li, Suning Li, Hongmei Gu, Qianfeng Lu, Wenjiao Jiang, Xue Pei, Yilin Sun, Hongjiang Xu, Guangji Wang, Kun Hao
To take full advantage of combination therapy of Docetaxel (DTX) and Magnesium isoglycyrrhizinate (MGIG), the pharmacokinetic- pharmacodynamic- toxicodynamics (PK-PD-TD) interaction of DTX and MGIG in non-small cell lung tumor-bearing mice was investigated in the present study. A model, an integrated semi-mechanistic PK-PD-TD, was established for elucidating the exposure-effect-toxicity relationship between DTX and MGIG. A tumor growth and a transit compartmental system were applied to imitate the growth and death of tumor cell...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136753/-metabolomics-study-of-tris-2-chloroethyl-phosphate-induced-hepaotoxicity-and-nephrotoxicity-in-sprague-dawley-rats
#7
W Q Yang, F Zhao, L Li, Y J Fang
Objective: To discuss the potential toxic target organ and the toxic effects and mechanisms of tris (2-chloroethyl) phosphate (TCEP) on SD rats. Methods: 40 female SD rats weaning from milk for 21 days, weighted (50±2.3)g were selected as subjects and marked by the weight. They were randomly divided into 4 groups, namely control group, 50 (L), 100 (M) and 250 (H) mg·kg(-1)·d(-1) dose of TCEP group. Each group has 10 rats, and administrated the corresponding dose of drug or vehicle by mouth, quaque die for 60 days...
November 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/29136249/natural-polyphenol-chlorogenic-acid-protects-against-acetaminophen-induced-hepatotoxicity-by-activating-erk-nrf2-antioxidative-pathway
#8
Mengjuan Wei, Zhiyong Zheng, Liang Shi, Yao Jin, Lili Ji
Hepatotoxicity due to acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in clinic. Chlorogenic acid (CGA), a dietary polyphenol, was reported to prevent APAP-induced liver injury in our previous studies. This study aims to investigate the protection provided by CGA against APAP-induced hepatotoxicity via focusing on nuclear factor erythroid 2-related factor 2 (Nrf2) and extracellular regulated protein kinases (ERK)1/2. CGA prevented APAP-induced oxidative liver injury and enhanced Nrf2 activation in mice and in hepatocytes in vitro...
November 10, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29129847/effects-of-ketoconazole-on-cyclophosphamide-metabolism-evaluation-of-cyp3a4-inhibition-effect-using-the-in-vitro-and-in-vivo-models
#9
Le Yang, Chenyang Yan, Feng Zhang, Bo Jiang, Shouhong Gao, Youtian Liang, Lifeng Huang, Wansheng Chen
Cyclophosphamide (CP) is widely used in anticancer therapy regimens and 2-dechloroethylcyclophosphamide (DECP) is its side-chain dechloroethylated metabolite. N-dechloroethylation of CP mediated by the enzyme CYP3A4 yields nephrotoxic and neurotoxic chloroacetaldehyde (CAA) in equimolar amount to DECP. This study aimed to evaluate the inhibitory effect of ketoconazole (KTZ) on CP metabolism through in vitro and in vivo drug-drug interaction (DDI) research. Long-term treatment of KTZ induces hepatic injury; thus single doses of KTZ at low, middle, and high levels (10, 20, and 40 mg/kg) were investigated for pharmacokinetic DDI with CP...
November 13, 2017: Experimental Animals
https://www.readbyqxmd.com/read/29129047/hepaprotective-effect-of-standardized-ecklonia-stolonifera-formulation-on-ccl%C3%A2-induced-liver-injury-in-sprague-dawley-rats
#10
Jae-Hyuk Byun, Jun Kim, Se-Young Choung
The liver is an essential organ for the detoxification of exogenous xenobiotics, drugs and toxic substances. The incidence rate of non-alcoholic liver injury increases due to dietary habit change and drug use increase. Our previous study demonstrated that Ecklonia stolonifera (ES) formulation has hepatoprotective effect against alcohol-induced liver injury in rat and tacrine-induced hepatotoxicity in HepG2 cells. This present study was designated to elucidate hepatoprotective effects of ES formulation against carbon tetrachloride (CCl₄)-induced liver injury in Sprague Dawley rat...
November 13, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29120909/rivaroxaban-induced-hepatotoxicity-review-of-the-literature-and-report-of-new-cases
#11
Anna Licata, Fania Puccia, Vania Lombardo, Antonietta Serruto, Maria G Minissale, Ilaria Morreale, Lydia Giannitrapani, Maurizio Soresi, Giuseppe Montalto, Piero L Almasio
AIM/OBJECTIVE/BACKGROUND: Direct-acting oral anticoagulant drugs are marketed worldwide for the primary and secondary prevention and treatment of thromboembolic disorders. Rivaroxaban, an oral, direct factor Xa inhibitor, is one of the most used. Rivaroxaban-induced hepatotoxicity is unusual, although a number of adverse reports have recently been reported. Here, we report two new cases of rivaroxaban-induced hepatitis. METHODS: A systematic search of case reports on the MEDLINE database encompassing the years 2008-2016 was carried out...
November 8, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29119413/identification-and-characterization-of-fenofibrate-induced-liver-injury
#12
Jawad Ahmad, Joseph A Odin, Paul H Hayashi, Naga Chalasani, Robert J Fontana, Huiman Barnhart, Elizabeth T Cirulli, David E Kleiner, Jay H Hoofnagle
BACKGROUND: Fenofibrate is a commonly used hypolipidemic associated with rare instances of hepatotoxicity, and routine liver biochemistry monitoring is recommended. AIMS: The aim of this study is to describe the presenting clinical features, liver histopathology, and outcomes of 7 cases of acute liver injury associated with fenofibrate. METHODS: All cases of definite, very likely, and probable drug-induced liver injury (DILI) attributed to fenofibrate enrolled in the DILI Network study between 2004 and 2015 were reviewed...
November 8, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29115483/hepatocellular-toxicity-of-oxalicumone-a-via-oxidative-stress-injury-and-mitochondrial-dysfunction-in-healthy-human-liver-cells
#13
Si Shi, Limei Yao, Kunbin Guo, Xiangyu Wang, Qi Wang, Weirong Li
The marine‑derived oxalicumone A (POA) has been demonstrated as a potent anti‑tumor bioactive agent for a variety of human carcinoma, but to the best of our knowledge, remains to be evaluated in healthy liver cells. As many drugs distribute preferentially in the liver, the present study aimed to investigate the effects of POA on apoptosis, oxidative stress and mitochondrial function in L‑02 healthy liver cells. A Cell‑Counting kit‑8 assay demonstrated that POA inhibits the proliferation of L‑02 cells in a dose‑ and time‑dependent manner...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29108197/-advances-in-clinical-differentiation-between-immunological-and-drug-induced-liver-injury
#14
Y Wang, Y N Li, J Zhang, B M Wang, L Zhou
The differentiation between autoimmune hepatitis (AIH) and drug-induced liver injury (DILI) is a difficult task in clinical practice. Some AIH patients had a medication history before disease onset, and some DILI patients may have positive serum antibody. In addition, these two groups of patients have similar clinical symptoms, serological examination results, and liver histopathology, which lead to the difficulties in differentiation. However, correct differential diagnosis is of great significance in making clinical treatment decisions and preventing liver cirrhosis...
September 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29106686/the-identification-of-pivotal-transcriptional-factors-mediating-cell-responses-to-drugs-with-drug-induced-liver-injury-liabilities
#15
Falgun Shah, Alex Medvedev, Anne Mai Wassermann, Marian Brodney, Liying Zhang, Sergei Makarov, Robert V Stanton
Drug-induced liver injury (DILI) is a leading cause of drug attrition during drug development and a common reason for drug withdrawal from the market. The poor predictability of conventional animal-based approaches (Olson et al. 2000) necessitates the development of alternative testing approaches. Body of evidence associates DILI with the induction of stress-response genes in the liver cells (Yuan and Kaplowitz 2013). Here, we set out to identify signal transduction pathways predominantly involved in the regulation of gene transcription by DILI drugs...
November 2, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29096561/in-silico-modeling-to-optimize-interpretation-of-liver-safety-biomarkers-in-clinical-trials
#16
Rachel J Church, Paul B Watkins
Current strategies to delineate the risk of serious drug-induced liver injury associated with drugs rely on assessment of serum biomarkers that have been utilized for many decades. In particular, serum alanine aminotransferase and total bilirubin levels are typically used to assess hepatic integrity and function, respectively. Parallel measurement of these biomarkers is utilized to identify patients with drug-induced hepatocellular jaundice ("Hy's Law" cases) which carries at least a 10% risk of death or liver transplant...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29093747/hepatoprotective-properties-of-penthorum-chinense-pursh-against-carbon-tetrachloride-induced-acute-liver-injury-in-mice
#17
Meng Wang, Xiao-Jiao Zhang, Ruibing Feng, Yun Jiang, Da-Yong Zhang, Chengwei He, Peng Li, Jian-Bo Wan
Background: Penthorum chinense Pursh (Penthoraceae, PCP), a well-known Miao ethnomedicine, has been traditionally used to treat several liver-related diseases, such as jaundice and viral hepatitis. The aims of the present study were to evaluate the probable properties of the aqueous extract of PCP on carbon tetrachloride (CCl4)-induced acute liver injury in mice. Methods: C57BL/6 mice were orally administered an aqueous extract of PCP (5.15 and 10.3 g/kg BW) or silymarin (100 mg/kg) once daily for 1 week prior to CCl4 exposure...
2017: Chinese Medicine
https://www.readbyqxmd.com/read/29091294/zebrafish-abcb11b-mutant-reveals-novel-strategies-to-restore-bile-excretion-impaired-by-bile-salt-export-pump-deficiency
#18
Jillian L Ellis, Kevin E Bove, Erin G Schuetz, Daniel Leino, C Alexander Valencia, John D Schuetz, Alexander Miethke, Chunyue Yin
Bile salt export pump BSEP (ABCB11) is a liver-specific adenosine triphosphate-cassette binding transporter that mediates canalicular bile salt excretion from hepatocytes. Human mutations in ABCB11 cause progressive familial intrahepatic cholestasis type II (PFIC2). Although over 150 ABCB11 variants have been reported, our understanding of their biological consequences is limited by the lack of experimental model that recapitulates the patient phenotypes. We applied CRISPR/Cas9-based genome editing technology to knockout abcb11b, the ortholog of human ABCB11, in zebrafish and found that these mutants died prematurely...
November 1, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29090555/-protective-effects-of-five-different-types-of-dendrobium-on-ccl4-induced-liver-injury-in-mice
#19
Kai Wang, Dan-Juan Sui, Chang-Suo Wang, Li Yang, Zhen Ouyang, Nai-Fu Chen, Bang-Xing Han, Yuan Wei
This study aims to investigate the protective effect of Dendrobium huoshanense, D.officinale(Huoshan), D.officinale(Yunnan), D.moniliforme and D. henanense on CCl4-induced hepatic damage in mice. C57BL/6 mice were randomly divided into control group, model group, high-dose(7.5 g•kg⁻¹) and low-dose (1.25 g•kg⁻¹) groups of the five Dendrobium. Each group was intragastrically administered with drugs for 2 weeks. The control group was intraperitoneally injected with Olive oil solution, while the other groups were intraperitoneally given 0...
May 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29090021/liver-injury-and-glatiramer-acetate-an-uncommon-association-case-report-and-literature-review
#20
REVIEW
Javier Almeida, Nuria Solà-Valls, Elisa Pose, Yolanda Blanco, María Sepúlveda, Sara Llufriu, Pere Gines, Albert Saiz
We report the case of a 65-year-old woman who presented with a 1-month history of progressive paraparesia associated with a thoracic lesion with irregular ring-like gadolinium enhancement. Biopsy of the lesion confirmed the demyelinating origin and brain magnetic resonance imaging showed additional lesions demonstrative of dissemination in space. Immunomodulatory therapy with glatiramer acetate (GA) was started after having a second relapse 2 months later. Shortly after initiation, the patient developed acute hepatitis...
November 2017: Therapeutic Advances in Neurological Disorders
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