Abstract：
:Several in vivo and in vitro studies have assessed methods of evaluating the cardio toxicity of compounds during drug development due to its importance for predicting human toxicity. However, in vivo/in vitro relationships have not yet been reported using a zebrafish model. This study determined the bradycardia of 15 compounds by evaluating the change in heart beat rate (HBR) in zebrafish, hERG fluorescence polarization (hERG-FP), and ionic current change using a patch clamp (hERG-PC). In addition, a model for prediction of drug-induced bradycardia was established using in vivo and in vitro assays designed for high-throughput toxicological screening. The IC(50) values correlated well in two in vitro studies (R(2)=0.9). The change in HBR in zebrafish caused by the compounds could be estimated using the IC(50) from the hERG-FP assay [(i.e., % of HBR=19.5×log(IC(50), hERG-FP)] or hERG-PC assay [(i.e., % of HBR=19.6×log(IC(50), hERG-FP)]. To validate the predictive model, 10 unknown compounds were used and the percentages of the HBR were estimated using the model. The observed and predicted HBR% for the compounds in zebrafish were well-correlated (R(2)=0.948). Therefore, the proposed models were useful for prediction of drug-induced bradycardia related cardio toxicity.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Park MJ,Lee KR,Shin DS,Chun HS,Kim CH,Ahn SH,Bae MAdoi
10.1016/j.toxlet.2012.10.018subject
Has Abstractpub_date
2013-01-10 00:00:00pages
9-15issue
1eissn
0378-4274issn
1879-3169pii
S0378-4274(12)01366-5journal_volume
216pub_type
杂志文章abstract：:Toxicokinetics is the assessment of systemic exposure in toxicity studies, in which pharmacokinetic data are generated, either as an integral component in the conduct of the nonclinical toxicity studies or in specially designed supportive studies, in order to assess systemic exposure. The data may be used in the inter...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(01)00272-7
更新日期：2001-03-31 00:00:00
abstract：:The effects of lead exposure have been studied upon the behavioural and diuretic responses to the kappa-opioid receptor agonist U-50488H in neonatal rats. Lead was administered in the maternal drinking water (100, 300 and 1000 ppm) from conception to postnatal day 14. The hyperactivity, wall climbing behaviours and di...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(90)90248-k
更新日期：1990-01-01 00:00:00
abstract：:The influence of cold exposure (+ 1 degree C for 24 h) was studied in rats dosed i.p. with 0, 2.5 or 5.0 mumol HgCl2/kg. Cold exposure of controls caused an increased diuresis and solute elimination, except sodium, with almost no variations in urine alkaline phosphatase (ALP) and gammaglutamyl transferase (GGT). Proxi...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(82)90067-4
更新日期：1982-02-01 00:00:00
abstract：:In connection with extensive health studies of employees from two big central waste disposal sites, cytogenetic investigations were performed. The subject of these special analyses was to examine whether the complex mixture of pollutants from waste disposal sites comprises a genotoxic hazardous potential. Cytogenetic ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(98)00062-9
更新日期：1998-08-01 00:00:00
abstract：:To understand environmental causes of disease, unbiased methods are needed to characterize the human exposome, which represents all toxicants to which people are exposed from both exogenous and endogenous sources. Because they directly modify DNA and important proteins, reactive electrophiles are probably the most imp...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.04.002
更新日期：2012-08-13 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：:We previously reported that NR2E3, an orphan nuclear receptor, plays an important role in maintaining the basal expression of estrogen receptor α (ER) and that the NR2E3 level is highly correlated with the relapse-free survival of breast cancer patients. Here, we investigated the role of NR2E3 in benzo(a)pyrene (BaP)-...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2015.06.1708
更新日期：2015-09-17 00:00:00
abstract：:Previous studies indicated that the enantiomers of thalidomide and its analogue EM12 exhibit differing teratogenic potencies. Unfortunately, these substances proved to be unstable and racemised considerably, so that the intrinsic teratogenic potencies of the pure enantiomers were difficult to elucidate. We have theref...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(89)90099-4
更新日期：1989-10-01 00:00:00
abstract：:The antioxidant activity of genistein is associated with preventing atherosclerosis; however, the underlying mechanisms are not fully understood. In this study, human umbilical vein endothelial cells (HUVECs) were pretreated with genistein at different concentrations (10nM, 100nM and 1000nM) for 6h and then exposed to...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2017.07.216
更新日期：2017-08-05 00:00:00
abstract：:Mutagenic activity of aflatoxin B1 (AFB1) was followed in the Ames Salmonella/microsome test using liver S-9 from control and partially hepatectomized (PH) mice. The S-9 preparations from the PH mice were capable of inducing significantly greater AFB1 mutagenic activity to strain TA100 than S-9 preparations from eithe...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(82)90060-1
更新日期：1982-12-01 00:00:00
abstract：:Betel quid chewing, which contributes high concentration of safrole in saliva, is a popular oral habit in Taiwan. Safrole is a documented rodent hepatocarcinogen, yet its hepatocarcinogenic potential in human is not known. Here, we used LC/ESI-ITMS(n) and LC/QTOF-MS confirmed safrole-dGMP as reference standard to dete...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2008.09.013
更新日期：2008-12-15 00:00:00
abstract：:The distribution of mercury to the brain following an injection of methylmercury (MeHg) or ethylmercury (EtHg) was examined in immature mice. Postnatal day (PND) 16 CD1 mice received MeHg chloride either by IM injection or by gavage. At 24 h and 7 days post-injection, total mercury concentrations were determined in bl...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2004.07.014
更新日期：2004-12-30 00:00:00
abstract：:The oxidation of styrene to styrene oxide and the hydration of this metabolite to styrene glycol was investigated in hepatocytes, 9000 x g supernatant (S9) and the microsomal fraction from rat liver. Similar amounts of free styrene oxide were found in microsomes, hepatocytes and S9. However, on the basis of the format...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(84)90120-6
更新日期：1984-11-01 00:00:00
abstract：:The effect of dietary vomitoxin on the serum IgA and IgG responses to two model intestinal antigens, casein and cholera toxin (CT), were assessed in 4 experimental groups: (1) mice fed casein-based diet, (2) mice fed casein-based diet containing 25 ppm vomitoxin, (3) mice fed casein-based diet and immunized with CT, a...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(90)90254-j
更新日期：1990-01-01 00:00:00
abstract：:Monitoring of human exposure to persistent organic pollutants POPs and heavy metals have taken place since 1994 in a circumpolar study conducted under the Arctic monitoring and assessment programme (AMAP). The study has confirmed that Arctic populations relying on marine food (Inuit) have an exposure level of POPs and...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/s0378-4274(99)00203-9
更新日期：2000-03-15 00:00:00
abstract：:The exposure to cuprizone (CPZ) leads to demyelination in the central nervous system in rodents. To examine the developmental effects of CPZ exposure on hippocampal neurogenesis, pregnant rats were treated with 0, 0.1 or 0.4% CPZ in the diet from gestational day 6 to day 21 after delivery. On postnatal day 21, male of...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2015.01.022
更新日期：2015-05-05 00:00:00
abstract：:Fructose-1,6-diphosphate (FDP) has a salutary effect on hemorrhagic, traumatic and endotoxic shock. The role of FDP on compound 48/80-induced shock was therefore investigated. Sprague Dawley aged male rats (448+/-7.4 gm body weight) were randomly assigned into three groups and treated intraperitoneally with diphenhydr...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(01)00357-5
更新日期：2001-06-20 00:00:00
abstract：:We investigated the effect of copper on cadmium-induced cytotoxicity on vascular endothelial cells from bovine aorta in a culture system. Cytotoxicity was evaluated by the [3H]adenine release assay and the histological observation. After a 24-h incubation, cadmium exhibited a significant cytotoxicity on confluent cult...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(92)90103-q
更新日期：1992-10-01 00:00:00
abstract：:3-Bromopyruvate (3-BrPA) is a promising agent that has been widely studied in the treatment of cancer and pulmonary hypertension. Rotenone is a pesticide commonly used on farms and was shown to have anti-cancer activity and delay fibrosis progression in chronic kidney disease in a recent study. However, there are few ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2019.09.024
更新日期：2020-01-01 00:00:00
abstract：:The cytogenetic effects of phenobarbitone were studied in the male germ cells of Swiss mice. The drug was orally administered at 42, 84 and 126 mg/kg body weight dose levels by sub-acute and chronic modes of treatment. In the treated series, the incidence of chromosome aberrations was significant at all dose levels. H...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(82)90002-9
更新日期：1982-11-01 00:00:00
abstract：:To determine whether occupational exposure to trichloroethylene (TCE) influences sympathetic nerve activity, serum dopamine-beta-hydroxylase (DBH) activities were analyzed in 84 male workers exposed to TCE and 83 male age-matched controls. The workers were exposed to about 22 ppm TCE in air. There were no significant ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(90)90187-q
更新日期：1990-12-01 00:00:00
abstract：:Mycotoxins and heavy metals are ubiquitous in the environment and contaminate many foods. The widespread use of pesticides in crop production to control disease contributes further to the chemical contamination of foods. Thus multiple chemical contaminants threaten the safety of many food commodities; hence the presen...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2015.07.006
更新日期：2015-10-01 00:00:00
abstract：:To investigate mechanisms of neuronal cell death in response to chlorpyrifos (CPF), a pesticide, we evaluated the regulation of ROS and COX-2 in human neuroblastoma SH-SY5Y cells treated with CPF. CPF treatment produced cytotoxic effects that appeared to involve an increase in ROS. In addition, CPF treatment activated...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2013.02.003
更新日期：2013-04-26 00:00:00
abstract：:Exposure of humans and animals to vesicants, including sulfur mustard (SM) and nitrogen mustard (NM), causes severe and debilitating damage to the respiratory tract. Both acute and long term pathological consequences are observed in the lung following a single exposure to these vesicants. Evidence from our laboratorie...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/j.toxlet.2015.10.011
更新日期：2016-02-26 00:00:00
abstract：OBJECTIVE:The aim of this investigation was to identify pathways involved in pneumoconiosis susceptibility, clarify their potential mechanisms, and generate SNP-to-gene to pathway hypotheses using an analytical pathway-based approach. METHODS:The identify candidate causal SNPs and pathways (ICSNPathway) was used to pe...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2014.10.028
更新日期：2015-01-05 00:00:00
abstract：:A wholesomeness feeding study was carried out in mice fed equal amounts of cod or redfish, comprising 45% of the diet. Three groups of animals received either irradiated [1.75 kGy (175 krad)] fish, non-irradiated fish or stock ration. A 90-day subchronic study, a multigeneration reproduction, a dominant lethality and ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(80)90039-9
更新日期：1980-12-01 00:00:00
abstract：:288 BALB/c male mice were allocated to: Group 1-control; Group 2-500 ppm of 2-acetylaminofluorene (2-AAF) in the food, with control water; Group 4-500 ppm of 2-AAF in the food and 250 mg/100 ml of vitamin C in the water; and Group 3-control food and 250 mg% of vitamin C in the water. Major histopathologic changes at t...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(80)90136-8
更新日期：1980-09-01 00:00:00
abstract：:We hypothesized that supraphysiological administration of the anabolic-androgenic steroids (AAS) like testosterone (TEST) and nandrolone decanoate (NAND) might differentially affect synaptic and extrasynaptic components of mitochondrial bioenergetics, thereby resulting in memory impairment. Oil (VEH), NAND or TEST (15...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2019.03.004
更新日期：2019-06-01 00:00:00
abstract：:Hormonally active chemicals in the human diet, such as man-made estrogenic chemicals or plant-derived compounds (phytoestrogens), have become a matter of public concern. A significant part of human exposure to phytoestrogens is attributable to soy isoflavones. Besides their estrogenic properties, soy isoflavones also ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2004.04.005
更新日期：2004-06-15 00:00:00
abstract：:Inflammation is one of the factors that may increase the sensitivity of hepatic cells to acetaminophen (APAP) induced toxicity. To investigate the mechanisms, we exposed 3-dimensional (3D) Human Liver Microtissues, a co-culture of primary human hepatocytes (PHH) and Kupffer cells (KCs), to 0, 0.5 (low), 5 (median) and...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2019.05.004
更新日期：2019-09-15 00:00:00
