Abstract：
:Intracellular retention of toxic bile salts contributes to hepatocellular injury during cholestasis. We have recently demonstrated that toxic bile salts directly induce apoptosis in hepatocytes. As oxidative stress has been implicated in many models of apoptosis, our aim was to determine if oxidative injury is a critical event during bile-salt-induced hepatocyte apoptosis. Cultured rat hepatocytes incubated with 50 microM glycochenodeoxycholate (GCDC) exhibited the characteristic morphological features of apoptosis such as nuclear fragmentation and cellular fragmentation into organelle-containing membrane-bound apoptotic bodies. After a 3-hr incubation, apoptosis was observed in 60 +/- 8% of cells compared to <1% in controls. GCDC-induced apoptosis was associated with lipid peroxidation as demonstrated by an increase in 8-isoprostane release. The antioxidant lazaroid U83836E inhibited 8-isoprostane generation during GCDC-induced hepatocye apoptosis. In addition, U83836E also reduced GCDC-mediated apoptosis by 70% as assessed using both stringent morpholgic (nuclear fragmentation) and biochemical (determination of DNA strand breaks) criteria. In summary, during treatment of hepatocytes with GCDC, (1) apoptosis is associated with lipid peroxidation, and (2) the antioxidant lazaroid U83836E inhibits both lipid peroxidation and apoptosis. In conclusion, these data suggest that oxidative stress contributes to bile-salt-induced apoptosis. We speculate that antioxidants may be useful in ameliorating liver injury during chronic cholestasis.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Patel T,Gores GJdoi
10.1006/taap.1996.8031subject
Has Abstractpub_date
1997-01-01 00:00:00pages
116-22issue
1eissn
0041-008Xissn
1096-0333pii
S0041-008X(96)98031-Xjournal_volume
142pub_type
杂志文章abstract：:Hexachlorobenzene (HCB)-induced porphyria occurs in female, but not male, rats after a delay of 35 days following HCB treatment. Uroporphyrinogen decarboxylase (UROD) inhibition has been proposed as a primary causative event. To determine whether there also exists a delay phase and a sexual dimorphism for UROD inhibit...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1997.8157
更新日期：1997-07-01 00:00:00
abstract：:Previously conducted reproduction and teratology studies in rats (unpublished observations) exposed to fluoxetine have revealed no compound-related adverse effects on fertility and no teratogenic effects. In order to confirm embryonic/fetal exposure to fluoxetine and/or metabolites, dissection and whole-body autoradio...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(89)90225-1
更新日期：1989-04-01 00:00:00
abstract：:Several pesticides and fungicides commonly used to control agricultural and indoor pests are highly suspected to display endocrine-disrupting effects in animals and humans. Endocrine disruption is mainly caused by the interference of chemicals at the level of steroid receptors: it is now well known that many of these ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2006.04.005
更新日期：2006-10-01 00:00:00
abstract：:Increased oxygen species production has often been cited as a mechanism determining synergism on cell death and growth inhibition effects of arsenic-combined drugs. However the net effect of drug combination may not be easily anticipated solely from available knowledge of drug-induced death mechanisms. We evaluated th...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2011.11.018
更新日期：2012-02-01 00:00:00
abstract：:Hepa 1c1c7 (WT), TAOc1BPrc1 (CI), and BPrc1 (CII) mouse hepatoma cells were exposed to benzo[e]pyrene (B[e]P) or benzo[a]pyrene (B[a]P). B[e]P induced activity of a rat CYP1A1 reporter gene construct (-3015 to +2545 bp) by 1.8- to 2-fold and 5-fold in WT and CI cells, respectively. B[e]P caused a 2-fold induction of a...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1994.1175
更新日期：1994-09-01 00:00:00
abstract：:Previous reports from our laboratory indicated that prophylactic protection against cyanide intoxication in mice can be enhanced by administration of chlorpromazine when it is given with sodium thiosulfate. The mechanism of potentiation of sodium thiosulfate by chlorpromazine was studied alone and in combination with ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(83)90028-5
更新日期：1983-12-01 00:00:00
abstract：:Metabonomics is the evaluation of the multiparametric metabolic response of biological systems to pathophysiological stimuli. High-resolution nuclear magnetic resonance (NMR) spectroscopy of biofluids coupled with pattern recognition-based chemometric analysis is an emerging approach to the study of metabonomics and m...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：
更新日期：2002-09-01 00:00:00
abstract：:During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec®). Imatinib targets PDGF, ABL-re...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2011.04.019
更新日期：2011-08-01 00:00:00
abstract：:The interaction of 1,1,1-trichloroethane (TCE), a widely used chlorocarbon solvent, on the metabolism and activation of [14C]-vinyl chloride in rat hepatic microsomes was investigated to determine the effects of combined exposures to these compounds. In microsomes from phenobarbital (PB)-treated rats, TCE increased vi...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1993.1039
更新日期：1993-03-01 00:00:00
abstract：:Marijuana or synthetic cannabinoids and alcohol are often used together, with these combinations causing motor impairments that can subsequently lead to motor vehicle accidents. This study investigated the combined use of both synthetic cannabinoids and ethanol and their effect on motor coordination in mice in additio...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2020.115283
更新日期：2020-12-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(83)90156-4
更新日期：1983-09-30 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/s0041-008x(03)00017-6
更新日期：2003-04-01 00:00:00
abstract：:The utility of isolated rat hepatocytes as a model system for screening potential chelators in treatment of Cd intoxication was studied. The ability of the chelators diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA), 2,3-dimercaptosuccinic acid (DMSA), diethyldithiocarbamic acid (DDC), ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(83)90232-6
更新日期：1983-02-01 00:00:00
abstract：:The differential effects of oral and dermal administration of single doses of 100 to 1000 mg/kg S,S,S-tri-n-butyl phosphorotrithioate (DEF) on nonspecific esterases and liver metabolism enzymes were investigated one day following administration. O,O-Diethyl O-(4-nitrophenyl) phosphorothioate (parathion) and tri-o-cres...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(84)90336-3
更新日期：1984-04-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2016.07.011
更新日期：2016-09-15 00:00:00
abstract：:Mice lacking the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in glutathione (GSH) synthesis, have decreased tissue GSH. We previously showed that Gclm-/- embryos have increased sensitivity to the prenatal in vivo ovarian toxicity of the polycyclic aromatic hydrocarbon benzo[a]pyrene ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2018.05.024
更新日期：2018-08-01 00:00:00
abstract：:The pharmacokinetics of methanol and formate were characterized in male Fischer-344 rats and rhesus monkeys exposed to methanol vapor concentrations between 50 and 2000 ppm for 6 hr. End-of-exposure blood methanol concentrations were not directly proportional to the atmospheric concentration. The methanol exposures di...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(92)90213-c
更新日期：1992-11-01 00:00:00
abstract：:A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) th...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2007.11.005
更新日期：2008-04-01 00:00:00
abstract：:Trichloroacetate (TCA) and dichloroacetate (DCA) have been shown to be hepatocarcinogenic in mice when administered in drinking water. However, DCA produces pathological effects in the liver that are much more severe than those observed following TCA treatment in both rats and mice. To identify potential mechanisms in...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(92)90332-m
更新日期：1992-08-01 00:00:00
abstract：:In rat skeletal muscle, chronic exposure to 50 ppm Cd2+ in drinking water produced both ultrastructural and functional damage, which took place successively and increased gradually with duration of treatment. Ultrastructurally, the first effect was a regression of the sarcoplasmic reticulum, mitochondrial cristae, and...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(85)90264-9
更新日期：1985-01-01 00:00:00
abstract：:We investigated the effects of JBP485 (an anti-inflammatory dipeptide and a substrate of OAT) on regulation of the expression and function of renal Oat1 and Oat3, which can accelerate the excretion of accumulated uremic toxins (e.g. indoxyl sulfate) in the kidney to improve gentamicin-induced ARF in rats. JBP485 cause...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2013.04.029
更新日期：2013-09-01 00:00:00
abstract：:Jaridonin, a novel diterpenoid from Isodon rubescens, has been shown previously to inhibit proliferation of esophageal squamous cancer cells (ESCC) through G2/M phase cell cycle arrest. However, the involved mechanism is not fully understood. In this study, we found that the cell cycle arrest by Jaridonin was associat...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2014.11.003
更新日期：2015-01-15 00:00:00
abstract：:Learning disabilities (LDs) in children are a serious global problem. Dibutyl phthalate (DBP), a plasticizer widely used in daily life, has been linked to triggering childhood LDs, however the mechanism underlying this remains unclear. Studies have shown that the ERK 1/2 pathway is closely related to apoptosis of hipp...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2019.02.008
更新日期：2019-04-01 00:00:00
abstract：:Acute exposure to Cd produces liver injury, whereas chronic exposure results in kidney injury. Tolerance to the hepatotoxicity is observed during chronic exposure to Cd due to the induction of metallothionein (MT). The nephrotoxicity produced by chronic Cd exposure purportedly results from renal uptake of Cd-metalloth...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(88)90231-1
更新日期：1988-01-01 00:00:00
abstract：:Gallium arsenide (GaAs), indium arsenide (InAs), and aluminium gallium arsenide (AlGaAs) are semiconductor applications. Although the increased use of these materials has raised concerns about occupational exposure to them, there is little information regarding the adverse health effects to workers arising from exposu...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.taap.2003.10.019
更新日期：2004-08-01 00:00:00
abstract：:Chlorhexidine (CHX), widely used as antiseptic and therapeutic agent in medicine and dentistry, has a toxic effect both in vivo and in vitro. The intrinsic mechanism underlying CHX-induced cytotoxicity in eukaryotic cells is, however, still unknown. A recent study from our laboratory has suggested that CHX may induce ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2008.10.012
更新日期：2009-01-15 00:00:00
abstract：:Acute oral toxicity of Cd (as cadmium chloride) was enhanced in rats fasted 24 hr, as shown by a markedly decreased LD50. To examine the relationship among Cd toxicity, hepatic glutathione (GSH), and metallothionein (MT) during fasting, rats were administered 75 mg Cd/kg orally 24 hr after fasting and euthanized after...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(90)90259-w
更新日期：1990-03-15 00:00:00
abstract：:Oxidative stress can lead to expression of inflammatory transcription factors, which are important regulatory elements in the induction of inflammatory responses. One of the transcription factors, nuclear transcription factor kappa-B (NF-κB) plays a significant role in the inflammation regulatory process. Inflammatory...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2014.04.021
更新日期：2014-07-15 00:00:00
abstract：:Beryllium (Be+2), a divalent metal ion, is toxic to both man and animal. Although the molecular basis for its toxicity is unknown, it is well established that micromolar concentrations of beryllium specifically inhibit certain enzymes. Previous in vitro studies have shown that the presence of ferritin, an iron-storage...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(86)90211-5
更新日期：1986-02-01 00:00:00
abstract：:Rodent bioassays indicate that B6C3F1 mice are more sensitive to the carcinogenicity of benzene than are rats. The urinary profile of benzene metabolites is different in rats vs mice. Mice produce higher proportions of hydroquinone conjugates and muconic acid, indicators of metabolism via pathways leading to putative ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(92)90078-7
更新日期：1992-06-01 00:00:00
