A novel near-infrared fluorescent light-up probe for tumor imaging and drug-induced liver injury detection

2019 ◽  
Vol 55 (17) ◽  
pp. 2541-2544 ◽  
Author(s):  
Xiaodong Zeng ◽  
Ziyang Chen ◽  
Lin Tang ◽  
Han Yang ◽  
Nan Liu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Near Infrared ◽  
Tumor Imaging ◽  
Fluorescence Probe ◽  
Fluorescent Light ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Nir Fluorescence

A novel light-up NIR fluorescence probe was developed and used for tumor and drug-induced liver injury imaging in vivo.

BODIPY-based near-infrared fluorescent probe for diagnosis drug-induced liver injury via imaging of HClO in cells and in vivo

2021 ◽  
pp. 110073
Author(s):  
Guanwen Fan ◽  
Nannan Wang ◽  
Jian Zhang ◽  
Xin Ji ◽  
Shuchun Qin ◽  
...  
Keyword(s):  
Liver Injury ◽  
Fluorescent Probe ◽  
Near Infrared ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
In Cells

scholarly journals In vivo imaging of leucine aminopeptidase activity in drug-induced liver injury and liver cancer via a near-infrared fluorescent probe

2017 ◽  
Vol 8 (5) ◽  
pp. 3479-3483 ◽  
Author(s):  
Xinyuan He ◽  
Lihong Li ◽  
Yu Fang ◽  
Wen Shi ◽  
Xiaohua Li ◽  
...  
Keyword(s):  
Liver Injury ◽  
Fluorescent Probe ◽  
In Vivo Imaging ◽  
Near Infrared ◽  
Leucine Aminopeptidase ◽  
Aminopeptidase Activity ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
First Time

The upregulation of leucine aminopeptidase in hepatopathy models is imaged in vivo for the first time with a near-infrared fluorescent probe.

Drug-induced liver injury classification model based on in vitro human transcriptomics and in vivo rat clinical chemistry data

2014 ◽  
Vol 2 (4) ◽  
pp. 63-70 ◽  
Author(s):  
Danyel Jennen ◽  
Jan Polman ◽  
Mark Bessem ◽  
Maarten Coonen ◽  
Joost van Delft ◽  
...  
Keyword(s):  
Liver Injury ◽  
Clinical Chemistry ◽  
Classification Model ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Chemistry Data ◽  
Model Based ◽  
Injury Classification

Lighting up alkaline phosphatase in drug-induced liver injury using a new chemiluminescence resonance energy transfer nanoprobe

2018 ◽  
Vol 54 (88) ◽  
pp. 12479-12482 ◽  
Author(s):  
Xueting Liu ◽  
Nannan Fan ◽  
Lijie Wu ◽  
Chuanchen Wu ◽  
Yongqing Zhou ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Energy Transfer ◽  
Liver Injury ◽  
Alkaline Phosphatase Level ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Ultra-sensitive imaging of the alkaline phosphatase levelin vivoin drug-induced liver injury with a new chemiluminescence resonance energy transfer nanoprobe.

Ginsenoside Rb1, A Major Saponin from Panax ginseng, Exerts Protective Effects Against Acetaminophen-Induced Hepatotoxicity in Mice

2019 ◽  
Vol 47 (08) ◽  
pp. 1815-1831 ◽  
Author(s):  
Shen Ren ◽  
Jing Leng ◽  
Xing-Yue Xu ◽  
Shuang Jiang ◽  
Ying-Ping Wang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Panax Ginseng ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Protective Effects ◽  
Ginsenoside Rb1 ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Oxide Synthase

Acute liver injury (ALI) induced by acetaminophen (APAP) is the main cause of drug-induced liver injury. Previous reports indicated liver failure could be alleviated by saponins (ginsenosides) from Panax ginseng against APAP-induced inflammatory responses in vivo. However, validation towards ginsenoside Rb1 as a major and marker saponin may protect liver from APAP-induced ALI and its mechanisms are poorly elucidated. In this study, the protective effects and the latent mechanisms of Rb1 action against APAP-induced hepatotoxicity were investigated. Rb1 was administered orally with 10[Formula: see text]mg/kg and 20[Formula: see text]mg/kg daily for 1 week before a single injection of APAP (250[Formula: see text]mg/kg, i.p.) 1[Formula: see text]h after the last treatment of Rb1. Serum alanine/aspartate aminotransferases (ALT/AST), liver glutathione (GSH) depletion, as well as the inflammatory cytokines, such as tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1[Formula: see text] (IL-1[Formula: see text]), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), were analyzed to indicate the underlying protective effects of Rb1 against APAP-induced hepatotoxicity with significant inflammatory responses. Histological examination further proved Rb1’s protective effects. Importantly, Rb1 mitigated the changes in the phosphorylation of MAPK and PI3K/Akt, as well as its downstream factor NF-[Formula: see text]B. In conclusion, experimental data clearly demonstrated that Rb1 exhibited a remarkable liver protective effect against APAP-induced ALI, partly through regulating MAPK and PI3K/Akt signaling pathways-mediated inflammatory responses.

Zucker Lean Rats With Hepatic Steatosis Recapitulate Asymptomatic Metabolic Syndrome and Exhibit Greater Sensitivity to Drug-Induced Liver Injury Compared With Standard Nonclinical Sprague-Dawley Rat Model

2020 ◽  
Vol 48 (8) ◽  
pp. 994-1007
Author(s):  
Timothy P. LaBranche ◽  
Anna K. Kopec ◽  
Srinivasa R. Mantena ◽  
Brett D. Hollingshead ◽  
Andrew W. Harrington ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Pharmaceutical Industry ◽  
Liver Injury ◽  
Hepatic Steatosis ◽  
Sprague Dawley ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Sd Rats ◽  
Normal Chow

Fatty liver disease is a potential risk factor for drug-induced liver injury (DILI). Despite advances in nonclinical in vitro and in vivo models to assess liver injury during drug development, the pharmaceutical industry is still plagued by idiosyncratic DILI. Here, we tested the hypothesis that certain features of asymptomatic metabolic syndrome (namely hepatic steatosis) increase the risk for DILI in certain phenotypes of the human population. Comparison of the Zucker Lean (ZL) and Zucker Fatty rats fed a high fat diet (HFD) revealed that HFD-fed ZL rats developed mild hepatic steatosis with compensatory hyperinsulinemia without increases in liver enzymes. We then challenged steatotic HFD-fed ZL rats and Sprague-Dawley (SD) rats fed normal chow, a nonclinical model widely used in the pharmaceutical industry, with acetaminophen overdose to induce liver injury. Observations in HFD-fed ZL rats included increased liver injury enzymes and greater incidence and severity of hepatic necrosis compared with similarly treated SD rats. The HFD-fed ZL rats also had disproportionately higher hepatic drug accumulation, which was linked with abnormal hepatocellular efflux transporter distribution. Here, we identify ZL rats with HFD-induced hepatic steatosis as a more sensitive nonclinical in vivo test system for modeling DILI compared with SD rats fed normal chow.

scholarly journals Current Perspective: 3D Spheroid Models Utilizing Human-Based Cells for Investigating Metabolism-Dependent Drug-Induced Liver Injury

2020 ◽  
Vol 2 ◽  
Author(s):  
Christopher R. Cox ◽  
Stephen Lynch ◽  
Christopher Goldring ◽  
Parveen Sharma
Keyword(s):  
Liver Injury ◽  
Pharmaceutical Companies ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Current Perspective ◽  
Dosing Regimens ◽  
Underlying Mechanisms ◽  
Approved Drugs

Drug-induced liver injury (DILI) remains a leading cause for the withdrawal of approved drugs. This has significant financial implications for pharmaceutical companies, places increasing strain on global health services, and causes harm to patients. For these reasons, it is essential that in-vitro liver models are capable of detecting DILI-positive compounds and their underlying mechanisms, prior to their approval and administration to patients or volunteers in clinical trials. Metabolism-dependent DILI is an important mechanism of drug-induced toxicity, which often involves the CYP450 family of enzymes, and is associated with the production of a chemically reactive metabolite and/or inefficient removal and accumulation of potentially toxic compounds. Unfortunately, many of the traditional in-vitro liver models fall short of their in-vivo counterparts, failing to recapitulate the mature hepatocyte phenotype, becoming metabolically incompetent, and lacking the longevity to investigate and detect metabolism-dependent DILI and those associated with chronic and repeat dosing regimens. Nevertheless, evidence is gathering to indicate that growing cells in 3D formats can increase the complexity of these models, promoting a more mature-hepatocyte phenotype and increasing their longevity, in vitro. This review will discuss the use of 3D in vitro models, namely spheroids, organoids, and perfusion-based systems to establish suitable liver models to investigate metabolism-dependent DILI.

scholarly journals TAMH: A Useful In Vitro Model for Assessing Hepatotoxic Mechanisms

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Madison Davis ◽  
Brendan D. Stamper
Keyword(s):  
Liver Injury ◽  
Transforming Growth Factor ◽  
Chemical Exposure ◽  
Health Concern ◽  
Hepatocellular Injury ◽  
Drug Induced ◽  
Endogenous Factors ◽  
Drug Induced Liver Injury

In vitro models for hepatotoxicity can be useful tools to predict in vivo responses. In this review, we discuss the use of the transforming growth factor-αtransgenic mouse hepatocyte (TAMH) cell line, which is an attractive model to study drug-induced liver injury due to its ability to retain a stable phenotype and express drug-metabolizing enzymes. Hepatotoxicity involves damage to the liver and is often associated with chemical exposure. Since the liver is a major site for drug metabolism, drug-induced liver injury is a serious health concern for certain agents. At the molecular level, various mechanisms may protect or harm the liver during drug-induced hepatocellular injury including signaling pathways and endogenous factors (e.g., Bcl-2, GSH, Nrf2, or MAPK). The interplay between these and other pathways in the hepatocyte can change upon drug or drug metabolite exposure leading to intracellular stress and eventually cell death and liver injury. This review focuses on mechanistic studies investigating drug-induced toxicity in the TAMH line and how alterations to hepatotoxic mechanisms in this model relate to the in vivo situation. The agents discussed herein include acetaminophen (APAP), tetrafluoroethylcysteine (TFEC), flutamide, PD0325901, lapatinib, and flupirtine.

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