Design and synthesis of acetaminophen probe APAP-P1 for identification of the toxicity targets thioredoxin reductase-1 in HepaRG cells

Shan Wang; Yu Tian; Shan Lu; Ruiying Wang; Hai Shang; Xuelian Zhang; Chenyang Zhang; Guibo Sun; Xudong Xu; Xiaobo Sun

doi:10.1039/c9ra00483a

Design and synthesis of acetaminophen probe APAP-P1 for identification of the toxicity targets thioredoxin reductase-1 in HepaRG cells

RSC Advances ◽

10.1039/c9ra00483a ◽

2019 ◽

Vol 9 (27) ◽

pp. 15224-15228

Author(s):

Shan Wang ◽

Yu Tian ◽

Shan Lu ◽

Ruiying Wang ◽

Hai Shang ◽

...

Keyword(s):

Liver Injury ◽

Drug Administration ◽

Drug Withdrawal ◽

Food And Drug Administration ◽

Thioredoxin Reductase ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Design And Synthesis ◽

Thioredoxin Reductase 1 ◽

Heparg Cells

Drug-induced liver injury is one of the main causes of drug non-approval and drug withdrawal by the Food and Drug Administration (FDA).

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Drug-Induced Liver Injury Associated with Lopinavir- Ritonavir in Patients with COVID-19: A Disproportionality Analysis of U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) Data

10.21203/rs.3.rs-490285/v1 ◽

2021 ◽

Author(s):

Huilin Tang ◽

Liyuan Zhou ◽

Xiaotong Li ◽

Alan C Kinlaw ◽

Jeff Y Yang ◽

...

Keyword(s):

Adverse Event ◽

Liver Injury ◽

Drug Administration ◽

Reporting System ◽

Adverse Event Reporting System ◽

Adverse Event Reporting ◽

Disproportionality Analysis ◽

Drug Induced ◽

Event Reporting ◽

Drug Induced Liver Injury

Abstract Background Liver injury has been documented independently in novel coronavirus disease 2019 (COVID-19) patients and patients treated with lopinavir-ritonavir. Objective to investigate the drug-induced liver injury associated with lopinavir-ritonavir among the patients with COVID-19. Methods We conducted a disproportionality analysis of US Food and Drug Administration Adverse Event Reporting System (FAERS) between 2020Q1 and 2020Q3 to evaluate the association between lopinavir-ritonavir and risk of drug-induced liver injury (or severe drug-induced liver injury) and calculated their reporting odds ratios (RORs) with 95% confidence intervals (CIs). Results A total of 1,754 reports of drug-induced liver injury in patients with COVID-19. The ROR for drug-induced liver injury was 1.4 (95% CI, 1.1–1.7), 3.6 (95% CI, 2.7–4.7), and 0.8 (95% CI, 0.7-1.0) when comparing lopinavir-ritonavir with all other drugs, hydroxychloroquine/chloroquine only, and remdesivir, respectively. For severe drug-induced liver injury, RORs for lopinavir-ritonavir provided evidence of an association compared with all other drugs (ROR, 4.9; 95% CI, 3.7–6.5), compared with hydroxychloroquine/chloroquine only (ROR, 4.3; 95% CI, 3.0-6.2), and compared with remdesivir (ROR, 10.4; 95% CI, 7.2–15.0). Conclusions In the FAERS, we observed a disproportional signal for severe drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19.

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A modified multiparametric assay using HepaRG cells for predicting the degree of drug-induced liver injury risk

Journal of Applied Toxicology ◽

10.1002/jat.3371 ◽

2016 ◽

Vol 37 (3) ◽

pp. 382-390 ◽

Cited By ~ 11

Author(s):

Takafumi Tomida ◽

Hayao Okamura ◽

Tsuyoshi Yokoi ◽

Yoshihiro Konno

Keyword(s):

Liver Injury ◽

Injury Risk ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Heparg Cells

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Usefulness of HepaRG cells in the mitochondrial function assay for the estimation of potential risk of idiosyncratic drug-induced liver injury

Fundamental Toxicological Sciences ◽

10.2131/fts.7.153 ◽

2020 ◽

Vol 7 (3) ◽

pp. 153-160

Author(s):

Keisuke Goda ◽

Taku Masuyama

Keyword(s):

Liver Injury ◽

Mitochondrial Function ◽

Potential Risk ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Heparg Cells

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Multiparametric assay using HepaRG cells for predicting drug-induced liver injury

Toxicology Letters ◽

10.1016/j.toxlet.2015.04.014 ◽

2015 ◽

Vol 236 (1) ◽

pp. 16-24 ◽

Cited By ~ 32

Author(s):

Takafumi Tomida ◽

Hayao Okamura ◽

Masahiro Satsukawa ◽

Tsuyoshi Yokoi ◽

Yoshihiro Konno

Keyword(s):

Liver Injury ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Heparg Cells

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Transcriptional, Functional, and Mechanistic Comparisons of Stem Cell–Derived Hepatocytes, HepaRG Cells, and Three-Dimensional Human Hepatocyte Spheroids as Predictive In Vitro Systems for Drug-Induced Liver Injury

Drug Metabolism and Disposition ◽

10.1124/dmd.116.074369 ◽

2017 ◽

Vol 45 (4) ◽

pp. 419-429 ◽

Cited By ~ 71

Author(s):

Catherine C. Bell ◽

Volker M. Lauschke ◽

Sabine U. Vorrink ◽

Henrik Palmgren ◽

Rodger Duffin ◽

...

Keyword(s):

Stem Cell ◽

Liver Injury ◽

Three Dimensional ◽

Human Hepatocyte ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Heparg Cells ◽

In Vitro Systems ◽

Hepatocyte Spheroids

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DILI-Stk: An ensemble model for the prediction of drug-induced liver injury of drug candidates

Current Bioinformatics ◽

10.2174/1574893617666211228113939 ◽

2021 ◽

Vol 17 ◽

Author(s):

Jingyu Lee ◽

Myeong-Sang Yu ◽

Dokyun Na

Keyword(s):

Drug Discovery ◽

Liver Injury ◽

In Silico ◽

Prediction Models ◽

Drug Withdrawal ◽

Learning Algorithm ◽

Public Access ◽

Ensemble Model ◽

Drug Induced ◽

Drug Induced Liver Injury

Background: Drug-induced liver injury (DILI) is a leading cause of drug failure, accounting for nearly 20% of drug withdrawal. Thus, there has been a great demand for in silico DILI prediction models for successful drug discovery. To date, various models have been developed for DILI prediction; however, building an accurate model for practical use in drug discovery remains challenging. Methods: We constructed an ensemble model composed of three high-performance DILI prediction models to utilize the unique advantage of each machine learning algorithm. Results: The ensemble model exhibited high predictive performance, with an area under the curve of 0.88, sensitivity of 0.83, specificity of 0.77, F1-score of 0.82, and accuracy of 0.80. When a test dataset collected from the literature was used to compare the performance of our model with publicly available DILI prediction models, our model achieved an accuracy of 0.77, sensitivity of 0.82, specificity of 0.72, and F1-score of 0.79, which were higher than those of the other DILI prediction models. As many published DILI prediction models are not available for public access, which hinders in silico drug discovery, we made our DILI prediction model publicly accessible (http://ssbio.cau.ac.kr/software/dili/). Conclusion: We expect that our ensemble model may facilitate advancements in drug discovery by providing a highly predictive model and reducing the drug withdrawal rate.

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Drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19: a disproportionality analysis of U.S. food and drug administration adverse event reporting system (FAERS) data

International Journal of Clinical Pharmacy ◽

10.1007/s11096-021-01311-5 ◽

2021 ◽

Author(s):

Huilin Tang ◽

Liyuan Zhou ◽

Xiaotong Li ◽

Alan C. Kinlaw ◽

Jeff Y. Yang ◽

...

Keyword(s):

Adverse Event ◽

Liver Injury ◽

Drug Administration ◽

Reporting System ◽

Adverse Event Reporting System ◽

Adverse Event Reporting ◽

Disproportionality Analysis ◽

Drug Induced ◽

Event Reporting ◽

Drug Induced Liver Injury

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Leberschaden unter oraler Antikoagulation, Statin- und ACE-Hemmertherapie

Praxis ◽

10.1024/1661-8157/a000298 ◽

2010 ◽

Vol 99 (21) ◽

pp. 1259-1265 ◽

Cited By ~ 2

Author(s):

Bruggisser ◽

Terraciano ◽

Rätz Bravo ◽

Haschke

Keyword(s):

Liver Injury ◽

Wird Eine ◽

Drug Induced ◽

Drug Induced Liver Injury

Ein 71-jähriger Patient stellt sich mit Epistaxis und ikterischen Skleren auf der Notfallstation vor. Der Patient steht unter einer Therapie mit Phenprocoumon, Atorvastatin und Perindopril. Anamnestisch besteht ein langjähriger Alkoholabusus. Laborchemisch werden massiv erhöhte Leberwerte (ALAT, Bilirubin) gesehen. Der INR ist unter oraler Antikoagulation und bei akuter Leberinsuffizienz >12. Die weiterführenden Abklärungen schliessen eine Virushepatitis und eine Autoimmunhepatitis aus. Nachdem eine Leberbiopsie durchgeführt werden kann, wird eine medikamentös-toxische Hepatitis, ausgelöst durch die Komedikation von Atorvastatin, Phenprocoumon und Perindopril bei durch Alkohol bereits vorgeschädigter Leber diagnostiziert. Epidemiologie, Pathophysiologie und Klink der medikamentös induzierten Leberschäden (drug induced liver injury, DILI), speziell von Coumarinen, Statinen und ACE-Hemmern werden im Anschluss an den Fallbericht diskutiert.

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