Abstract：
:A quantitative high-content screening (HCS) was suggested for the real-time monitoring of drug-induced mitochondrial dysfunction-mediated hepatotoxicity. This HCS is very advantageous in that it allows simultaneous observation of drug-induced activations of hepatotoxic pathways using hypermulticolor cellular imaging. The mitochondrial permeability transition (MPT), cytosolic calcium, and caspase-3 were selected as functional markers to verify drug-induced hepatotoxicity and were concurrently monitored in HepG2 cells in a real-time manner. Nefazodone, tolcapone, and troglitazone caused mitochondrial dysfunction and subsequent apoptotic HepG2 cell death in addition to marked cytosolic calcium increase. On the other hand, extrinsic pathway-mediated apoptotic cell death was monitored when HepG2 cells were treated with piroxicam. It was found that piroxicam-treated HepG2 cells showed apoptotic cell death without the MPT formation, while a cytosolic calcium increase was clearly observed. This finding was confirmed by the caspase-8 inhibition assay. These results demonstrated the unique potential of real-time hypermulticolor HCS to screen hepatotoxic drugs at the in vitro stage rather than the later in vivo stage based on an animal model and to ultimately reduce the probability of drug failure.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Kim JA,Han E,Eun CJ,Tak YK,Song JMdoi
10.1016/j.toxlet.2012.08.027subject
Has Abstractpub_date
2012-10-17 00:00:00pages
175-81issue
2eissn
0378-4274issn
1879-3169pii
S0378-4274(12)01283-0journal_volume
214pub_type
杂志文章abstract：:Safety assessment procedures still rely heavily if not exclusively on the results of tests carried out in laboratory animals, then extrapolated to man. There are few examples of environmental compounds examined extensively enough in both man and animals to permit a critical comparison of the accuracy of such risk asse...
journal_title：Toxicology letters
pub_type： 杂志文章
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pub_type： 杂志文章,评审
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journal_title：Toxicology letters
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journal_title：Toxicology letters
pub_type： 杂志文章
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更新日期：2015-11-19 00:00:00
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.01.019
更新日期：2018-05-01 00:00:00
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journal_title：Toxicology letters
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2003.09.021
更新日期：2005-03-28 00:00:00
abstract：:Intraperitoneal injection (50 mg/kg) of 2-nitropropane (2-NP) induced lipid accumulation, centrilobular necrosis, degranulation of rough endoplasmic reticulum, proliferation of smooth endoplasmic reticulum and mitochondrial abnormalities in rat liver 24 h after exposure. These pathological changes were accompanied by ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(81)90156-9
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abstract：:DNA-damaging agents are commonly used as anticancer therapeutics. Unfortunately, such drugs induced DNA damages as well as DNA repair are important in mediating drug resistance to cancer treatments. To evaluate changes in DNA repair proteins that occur in DNA damage agent treatment, we challenged human A549 lung adeno...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.06.028
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journal_title：Toxicology letters
pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2005.10.024
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abstract：:New findings on Bisphenol A (BPA) contents in thermal printing papers, and receipts, in g/kg concentrations and on its dermal uptake (up to 60%) prompted us to assess the risk arising from dermal exposure. Using physiologically based toxicokinetic modelling, we simulated concentrations in blood, in liver and kidney, t...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.04.032
更新日期：2011-07-28 00:00:00
abstract：:Dysglycemia and central nervous system (CNS) complications are the known adverse effects of fluoroquinolone antibiotics. Ciprofloxacin and levofloxacin are among the most prescribed antibiotics. In this study we demonstrate that ciprofloxacin and levofloxacin disturb glucose transport into HepG2 cells and such inhibit...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2008.10.017
更新日期：2009-01-30 00:00:00
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(82)90177-1
更新日期：1982-07-01 00:00:00
abstract：:Morusin is a prenylated flavonoid that has been isolated from the root bark of the mulberry tree (Morus species, Moraceae), a Chinese traditional medicine. It has been synthesized by our laboratory from commercially available phloroglucinol, and has demonstrated to possess antitumor effects of cell lines including A54...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2014.11.031
更新日期：2015-01-22 00:00:00
abstract：:A comparative evaluation of urinary biomarkers was carried out to characterize benzene exposure in a group of 100 traffic policemen of the city of Parma (Italy). All subjects were monitored once, in two consecutive days characterized by similar climatic conditions but preceded by two windy days. Benzene ambient concen...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2008.06.865
更新日期：2008-09-01 00:00:00
abstract：:Morphological malformations induced by tributyltin (TBT) exposure during embryonic development have already been characterized in various taxonomic groups, but, nonetheless, the molecular processes underlying these changes remain obscure. The present study provides the first genome-wide screening for differentially ex...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2017.11.019
更新日期：2018-03-01 00:00:00
abstract：:Mouse neuroblastoma cells exposed to 2.5 and 5.0 microM methylmercury for 24 h appeared rounded with the loss of processes. Immunohistochemical staining directed against beta-tubulin revealed severe alterations in microtubular architecture. Non-membrane-bound condensation product was visualized ultrastructurally in th...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(90)90226-c
更新日期：1990-03-01 00:00:00
abstract：BACKGROUND:Vitamin A is widely used in cosmetic preparations. Given that oral Vitamin A and its metabolites present a potential reproductive risk, the present study investigated the effect of topical Vitamin A on human endogenous plasma levels of Vitamin A and its metabolites. METHODS:Two groups of 14 female volunteer...
journal_title：Toxicology letters
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.toxlet.2005.09.029
更新日期：2006-05-05 00:00:00
abstract：:Ursolic acid (UA), a pentacyclic triterpene acid, is reported to have inducing activity of hepatic metallothionein (MT) which responsible for the detoxification of heavy metals; however, the mechanism underlying its effects is poorly understood. To further determine the underlying mechanism of UA, this study investiga...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2004.11.002
更新日期：2005-03-15 00:00:00
