Abstract:
:Use of the fluoroquinolone antibiotic trovafloxacin (TVX) was restricted due to idiosyncratic, drug-induced liver injury (IDILI). Previous studies demonstrated that tumor necrosis factor-alpha (TNF) and TVX interact to cause death of hepatocytes in vitro that was associated with prolonged activation of c-Jun N-terminal kinase (JNK), activation of caspases 9 and 3, and DNA damage. The purpose of this study was to explore further the mechanism by which TVX interacts with TNF to cause cytotoxicity. Treatment with TVX caused cell cycle arrest, enhanced expression of p21 and impaired proliferation, but cell death only occurred after cotreatment with TVX and TNF. Cell death involved activation of extracellular signal-related kinase (ERK), which in turn activated caspase 3 and ataxia telangiectasia and Rad3-related (ATR), both of which contributed to cytotoxicity. Cotreatment of HepG2 cells with TVX and TNF caused double-strand breaks in DNA, and ERK contributed to this effect. Inhibition of caspase activity abolished the DNA strand breaks. The data suggest a complex interaction of TVX and TNF in which TVX causes replication stress, and the downstream effects are exacerbated by TNF, leading to hepatocellular death. These results raise the possibility that IDILI from TVX results from MAPK and ATR activation in hepatocytes initiated by interaction of cytokine signaling with drug-induced replication stress.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Beggs KM,Maiuri AR,Fullerton AM,Poulsen KL,Breier AB,Ganey PE,Roth RAdoi
10.1016/j.tox.2015.03.002subject
Has Abstractpub_date
2015-05-04 00:00:00pages
35-46eissn
0300-483Xissn
1879-3185pii
S0300-483X(15)00053-0journal_volume
331pub_type
杂志文章相关文献
TOXICOLOGY文献大全abstract::Gambogic acid (GA), a major active component of gamboge, exhibits potent anticancer activity in many kinds of cancer cells. However, the anticancer mechanism of GA is not clearly understood. Here we showed that GA could cause growth inhibition, induce the G0/G1 phase cell cycle arrest and apoptosis in human chronic my...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2009.04.059
更新日期:2009-08-03 00:00:00
abstract::Trichloroacetic acid, TCA, is a water chlorination by-product similar to dichloroacetic acid, DCA. Because DCA has been shown to have effects on intermediary metabolism, TCA was tested to determine if it possesses similar capabilities. The effects were more pronounced in females. High doses of TCA (2.45 mumol/kg three...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(90)90069-s
更新日期:1990-07-01 00:00:00
abstract::Nine structurally different polycyclic aromatic hydrocarbons (PAHs) were tested for their ability to either agonize or antagonize the human androgen receptor (hAR) in a sensitive reporter gene assay based on CHO cells transiently cotransfected with a hAR vector and an MMTV-LUC vector. Benz[a]anthracene (B[a]A), benzo[...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(00)00143-8
更新日期:2000-04-14 00:00:00
abstract::Certain derivatives of p-phenylenediamine have been shown to cause necrosis of cardiac and skeletal muscle in rats; in vitro, such compounds are known to autoxidize to the corresponding radical cations, with concomitant formation of oxygen free-radicals. In the present study, the autoxidation rates of p-phenylenediami...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(89)90118-2
更新日期:1989-08-01 00:00:00
abstract::Aerolysin is a cytolytic toxin which forms channels in the plasma membranes of eucaryotic cells. The protein is secreted by Aeromonas hydrophila as an inactive protoxin. Its stability and water solubility are conferred by its ability to dimerize. Maturation of the protein occurs through proteolytic removal of a C-term...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/0300-483x(94)90152-x
更新日期:1994-02-28 00:00:00
abstract::Chalcones are phenolic compounds that can be isolated from plants. Previous studies have described some pharmacological applications for these compounds. Making use of our established reporter gene system, we determined the effect of five hydroxychalcones--2-hydroxychalcone, 2'-hydroxychalcone, 4-hydroxychalcone, 4,2'...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2004.10.005
更新日期:2005-02-14 00:00:00
abstract::Valproic acid (VPA) and the unsaturated metabolites, 2-ene VPA and (E)-2,(Z)-3'-diene VPA, demonstrated dose-dependent cytotoxicity in primary cultures of rat hepatocytes, as evaluated by lactate dehydrogenase (LDH) leakage. Cellular glutathione (GSH) was depleted by adding buthionine sulfoximine (BSO) to the culture ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(96)03352-5
更新日期:1996-08-01 00:00:00
abstract::Hesperidin (HDN) is a flavanone glycoside abundantly found in citrus fruits. HDN has been reported to possess significant activities against allergy, haemorrhoids, hormonal disorders and ulcers. Other reported activities include anti-inflammatory, analgesic, antibacterial, antifungal, antiviral, antioxidant and free r...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2006.06.018
更新日期:2006-09-21 00:00:00
abstract::A single oral administration of O, O, S-trimethyl phosphorothioate (OOS-Me), an impurity in widely used organophosphorus insecticides, causes delayed toxicity (delayed death) which is accompanied by morphological changes in the bronchiolar epithelium of rat lungs. A series of simple O,O-dimethyl and O,O-diethyl S-alky...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(84)90032-5
更新日期:1984-07-01 00:00:00
abstract::Technical pentabrominated diphenyl ether (pentaBDE mix) is a mixture of polybrominated diphenyl ethers (PBDEs) which has been widely used as a flame retardant. Since its ban in several countries it has been replaced by other brominated flame retardants such as hexabromocyclododecane (HBCD). Both certain PBDE congeners...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2009.07.009
更新日期:2009-10-01 00:00:00
abstract::The measurement of levels of organic pollutants and/or their metabolites in body tissues or fluids are specific markers of internal dose and, provided that the pharmacokinetic properties of the compounds in question are known, these levels may also be used as predictors of effects. Although historical data still remai...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/0300-483x(95)03017-a
更新日期:1995-07-26 00:00:00
abstract::4-Amino-2,6-dichlorophenol (ADCP) is a potent acute nephrotoxicant in vivo inducing prominent renal corticomedullary necrosis. In vitro, ADCP exposure increases lactate dehydrogenase (LDH) release from rat renal cortical slices at 0.05 mM or greater. The purpose of this study was to examine the ability of antioxidants...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2007.12.014
更新日期:2008-03-12 00:00:00
abstract::Pyrethroids are a class of insecticides involved in different neurological disorders. They cross the blood-brain barrier and exert their effect on dopaminergic system, contributing to the burden of oxidative stress in Parkinson's disease through several pathways. The aim of the present study was to evaluate the effect...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2006.10.015
更新日期:2007-01-18 00:00:00
abstract::Trichloroethylene (TCE) produced bronchiolar damage when administered to mice. Administration of 2000 mg/kg caused injury in Clara cells of the bronchiolar epithelium, which was observed at 24 h following TCE treatment; increase of the dosage to 2500 mg/kg induced additionally, alterations in alveolar Type II cells of...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(85)90028-9
更新日期:1985-05-01 00:00:00
abstract::The effects of zinc and copper on delta-aminolaevulinic acid dehydratase were studied in vitro and in vivo. The in vitro addition of zinc alone to whole blood resulted in a highly significant increase in enzyme activity. The addition of copper alone had the opposite effect with a significant decrease in enzyme activit...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(81)90161-x
更新日期:1981-01-01 00:00:00
abstract::Previous work has indicated that testosterone pretreatment protects against cadmium-induced toxicity in male rats while other data indicate that pretreatment of mice with testosterone offers no such protection against cadmium. Since cadmium toxicity may vary widely with species and strain, we examined the effect of te...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(96)03544-5
更新日期:1997-01-15 00:00:00
abstract::Studies showed that certain cytotoxicity assays were not suitable for assessing nanoparticle (NP) toxicity. We evaluated a lactate dehydrogenase (LDH) assay for assessing copper (Cu-40, 40nm), silver (Ag-35, 35nm; Ag-40, 40nm), and titanium dioxide (TiO(2)-25, 25nm) NPs by examining their potential to inactivate LDH a...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2011.06.011
更新日期:2011-09-05 00:00:00
abstract::The use of zinc as a nutritional supplement has become common in many countries. Since zinc has diverse actions, it may be difficult to predict its synergistic and/or antagonistic action in simultaneous presence of drug(s). The combination of imidazole antifungals, but not triazole antifungals, with 3-30 microM ZnCl2 ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2008.03.022
更新日期:2008-06-27 00:00:00
abstract::Double-stranded RNA-dependent protein kinase (PKR) is a component of signal transduction pathways mediating various stress signals including oxidative stress and endoplasmic reticulum (ER) stress and is suggested to be implicated in several neurodegenerative diseases. Cell death in neurodegenerative conditions has bee...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2019.02.012
更新日期:2019-04-15 00:00:00
abstract::We have found that incubation of heparin plasma with Ni(2+) or Co(2+) at concentrations below 100 microM can stimulate the conversion of complement factor C3 to C3b faster than magnesium, which is the natural cofactor in the alternative complement activation. This conversion was monitored by light absorbance measureme...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(02)00590-5
更新日期:2003-03-14 00:00:00
abstract::Ursodeoxycholic acid (UDCA) has been widely used for treating cholestatic liver diseases. However, in a recent review of clinical trial articles, its therapeutic benefits were not proven. Therefore, we investigated whether UDCA prevents or potentiates glycochenodeoxycholic acid (GCDCA)-induced apoptosis in isolated ra...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2005.05.025
更新日期:2005-10-15 00:00:00
abstract::Cadmium, an environmental neurotoxic compound, produces cognitive disorders, although the mechanism remains unknown. Previously, we described that cadmium induces a more pronounced cell death on cholinergic neurons from basal forebrain (BF). This effect, partially mediated by M1 receptor blockade, triggering it throug...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2017.12.006
更新日期:2018-02-01 00:00:00
abstract::A CYP3A4 promoter-reporter gene construct has been used to assess the ability of 16 known (in vivo) and putative (in vitro) inducers to transactivate a CYP3A4 reporter gene in HepG2 cells. With the exception of pravastatin, the remaining 15 compounds transactivated the CYP3A4 reporter gene with differing inductive abi...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(02)00281-0
更新日期:2002-12-27 00:00:00
abstract::Osteoblasts dysfunction, induced by aluminum (Al), plays a critical role in the osteoporosis etiology. Ginsenoside Rb1 (Rb1) has the therapeutic properties for osteoporosis. This study aimed to assess the efficiency of Rb1 in ameliorating Al-induced osteoblasts dysfunction. The osteoblasts were divided into four group...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2016.07.014
更新日期:2016-08-10 00:00:00
abstract::Twenty adult ewes underwent common surgery and following recovery were exposed to 1% carbon monoxide (CO) for 2 h. Ten of these sheep were randomly selected for treatment with haem oxygenase (HO) and nitric oxide synthetase (NOS) blockers. All sheep were killed 5 days later. The CO exposure was narcotic and EEG freque...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2004.12.033
更新日期:2005-05-05 00:00:00
abstract::Resistance to chemotherapy is a major obstacle for the effective treatment of cancers. The mechanism of chemo-resistance is still poorly understood, however, mounting evidence supports a role for microRNAs (miRNAs) in modulating key cellular pathways mediating response to chemotherapy. microRNA-21 (miR-21) has been im...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2013.02.014
更新日期:2013-04-05 00:00:00
abstract::Quartz is a well-known occupational fibrogenic agent able to cause fibrosis and other severe pulmonary diseases such as silicosis and lung cancer. The silicotic pathology owes its severity to the structural and chemo-physical properties of the particles such as shape, size and abundance of surface radicals. In earlier...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2016.07.001
更新日期:2016-06-15 00:00:00
abstract::To elucidate factors responsible for altered proliferation of preneoplastic hepatocytes in rat hepatocarcinogenesis in vivo, EGF-stimulated DNA synthesis of normal and nodular hepatocytes in primary culture was studied. In addition, the influence of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated to clari...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(99)00189-4
更新日期:2000-04-03 00:00:00
abstract::Although it is well known that microcystin-LR (MC-LR) may cause male reproductive toxicity, less is known on its potential impact on the development of prostate. In this study, from the 12th day in the embryonic period to the 21st day after birth, 4 randomly assigned groups of pregnant mice were exposed to 0, 1, 10, a...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2017.02.004
更新日期:2017-04-01 00:00:00
abstract::The influence of pretreatment with the drug mixture (pyridostigmine, benactyzine and trihexyphenidyle), and antidotal treatment (the oxime HI-6 in combination with benactyzine) on respiration, circulation and survival of experimental animals poisoned with supralethal doses of soman (2 x LD50) was investigated in a rat...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(97)00186-8
更新日期:1998-06-26 00:00:00