Abstract:
:Reactive oxygen species (ROS) have been implicated in various pulmonary diseases by causing direct injury to lung epithelial cells. Signalling activity of cells through transcription factors such as nuclear factor kappa B (NF-kappaB) and AP-1 have been shown to be regulated by ROS, and the release of pro-inflammatory cytokines demonstrated in the study of inflammatory disease. In this study, we examined the effect of the oxidant tert-butylhydroperoxide (tBHP) on mouse J774 macrophages and its ability to cause the release of the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha). The role of calcium as a signalling molecule was studied using various calcium antagonists. The role of the signalling molecule cAMP was also investigated using phosphodiesterase inhibitors PDE1 and PDE4 families. Oxidative stress was investigated in lung epithelial (A549) cells with and without calcium antagonists and PDE inhibitors with regard to their ability to modulate release of the neutrophil chemoattractant interleukin 8 (IL-8). The oxidant tBHP significantly increased the cytosolic calcium concentration in J774 macrophages, which was prevented by the PDE1 inhibitor. The production of TNF-alpha protein by J774 macrophages was mediated by a pathway involving calcium as addition of calcium antagonists inhibited the tBHP stimulated increase in the cytokine. Inhibitors of both PDE1 and PDE4 completely prevented the tBHP stimulated TNF-alpha release suggesting that the cAMP pathway may be important in the oxidant induced signalling pathway leading to gene expression of pro-inflammatory cytokines. In the presence of oxidant alone, A549 epithelial cells released significant amounts of IL-8, which was inhibited by both calcium antagonist treatment and PDE inhibition treatment. These data suggest that ROS-mediated lung inflammation could be mediated at least in part by calcium and elevated PDE activity associated with decreased cAMP in both macrophages and epithelial cells. Inhibition of these pathways may provide a route for treatment of inflammatory lung diseases.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Brown DM,Hutchison L,Donaldson K,MacKenzie SJ,Dick CA,Stone Vdoi
10.1016/j.toxlet.2006.10.016subject
Has Abstractpub_date
2007-01-10 00:00:00pages
1-6issue
1eissn
0378-4274issn
1879-3169pii
S0378-4274(06)01296-3journal_volume
168pub_type
杂志文章abstract::The effect of lead exposure on dopaminergic mechanisms regulating prolactin (PRL) secretion was studied in rats by measuring dopamine (DA) and dihydroxyphenylacetic acid hypothalamic concentrations and DA receptor density in the hypothalamus and pituitary of lead-exposed animals. [3H]Sulpiride was used as dopamine rec...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(84)90154-1
更新日期:1984-03-01 00:00:00
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
doi:10.1016/0378-4274(92)90236-d
更新日期:1992-12-01 00:00:00
abstract::The repeated use of the nerve agent sarin against civilians in Syria in 2013 emphasizes the continuing threat by chemical warfare agents. Multiple studies demonstrated a limited efficacy of standard atropine-oxime treatment in nerve agent poisoning and called for the development of alternative and more effective treat...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/j.toxlet.2015.07.012
更新日期:2016-02-26 00:00:00
abstract::The effects of linolic acid hydroperoxides (product A) and secondary oxidative products of product A (product B), were examined in an in vivo mid-term test for hepatocarcinogens or hepatopromoters in rats. The number of placental type of glutathione S-transferase (GST-P)-positive foci of the liver was significantly re...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(86)90048-2
更新日期:1986-07-01 00:00:00
abstract::Phenathrene is a major coal tar component found in hazardous waste disposal sites. The purpose of this study was to evaluate the extent to which phenanthrene adsorption to either of 2 different soils affects the manner in which phenanthrene is subsequently handled in orally and dermally exposed adult female rats. Abso...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(95)03250-o
更新日期:1995-07-01 00:00:00
abstract::Male rats are the most frequently used experimental animals in drug toxicity tests. However, there are clear sex-related differences in toxicity of various drugs and chemicals in rats. These differences, in most cases, are closely connected with the sex-related differences in hepatic drug metabolisms. Recent studies i...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/0378-4274(92)90245-f
更新日期:1992-12-01 00:00:00
abstract::Hyperbilirubinemia is a common clinical phenomenon observed in human newborns. A high level of bilirubin can result in severe jaundice and bilirubin encephalopathy. However, the cellular mechanisms underlying bilirubin excitotoxicity are unclear. Our previous studies showed the action of gamma-aminobutyric acid (GABA)...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2015.10.008
更新日期:2016-01-05 00:00:00
abstract::Amiodarone is an effective antidysrhythmic agent, restricted in use by the development of pulmonary toxicity. Several in vivo animal models have been used to study amiodarone-induced pulmonary toxicity. Intratracheal administration of amiodarone to the hamster has been used as a model for the critical amiodarone-induc...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(94)90073-6
更新日期:1994-10-01 00:00:00
abstract::Even though compounds of nickel, arsenic, cobalt and cadmium are carcinogenic, their mutagenic potentials are rather weak. In contrast, they exert pronounced comutagenic effects, which may be explained by disturbances of different DNA repair systems. Thus, cobalt, arsenic, nickel and cadmium interfere with base and nu...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/s0378-4274(01)00482-9
更新日期:2002-02-28 00:00:00
abstract::Physiologically based kinetic (PBK) models for farm animals are of growing interest in food and feed safety with key applications for regulated compounds including quantification of tissue concentrations, kinetic parameters and the setting of safe exposure levels on an internal dose basis. The development and applicat...
journal_title:Toxicology letters
pub_type: 杂志文章,meta分析
doi:10.1016/j.toxlet.2019.10.021
更新日期:2020-02-01 00:00:00
abstract::Transgenic rodents that contain easily retrievable target genes allow the rapid quantitation of mutations in any tissue from which DNA can be isolated. We are using the Stratagene Big Blue transgenic mouse system that contains a lacI target and an alpha lacZ reporter gene to study the parameters that affect mutations....
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/0378-4274(95)03472-2
更新日期:1995-12-01 00:00:00
abstract::Fluorocarbons containing chlorine or bromine have been associated with stratospheric ozone depletion and the search for suitable alternatives is progressing at an accelerated pace. The Program for Alternative Fluorocarbon Toxicity Testing (PAFT), an international group representing most of the world's CFC producers, h...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(93)90115-e
更新日期:1993-05-01 00:00:00
abstract::Zinc oxide NPs (ZnO) have been recently proposed as novel candidates for the treatment of allergic inflammatory diseases. Paradoxically, recent data suggested that ZnO could cause eosinophilic airway inflammation in rodents. Despite the above observations, there are currently no studies reporting direct interaction be...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2016.07.020
更新日期:2016-09-30 00:00:00
abstract::Aminoglycoside antibiotics play an integral role in antimicrobial chemotherapy. Unfortunately, these drugs are known to cause nephrotoxicity in man and experimental animals. In fact, the incidence of renal dysfunction during the course of clinical treatment with aminoglycoside antibiotics is approximately 10%. Over th...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/0378-4274(90)90067-v
更新日期:1990-05-01 00:00:00
abstract::The aim of this study was to determine the toxicokinetics and some effects of 1,1,1-trifluoroethane (HFC-143a) in humans. Nine male volunteers were experimentally exposed to 500ppm HFC-143a for 2h during light physical exercise (50W) in an exposure chamber. Blood, urine and exhaled air were sampled before, during and ...
journal_title:Toxicology letters
pub_type: 临床试验,杂志文章
doi:10.1016/j.toxlet.2007.05.010
更新日期:2007-08-01 00:00:00
abstract::In vivo effects of model cadmium-containing silica nanoparticles (SiNPs-Cd, 1 mg/rat) were investigated by i.t. instillation in rats to evaluate potential effects on secondary target organ, e.g., kidney. Specific endpoints and pathological outcomes were focused to assess inflammation and fibrosis in renal tissue, 7 an...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2014.11.021
更新日期:2015-01-22 00:00:00
abstract::High mobility group box 1 (HMGB1) is a DNA-binding protein that is abundantly expressed in most tissues. Recently, HMGB1 has gained much attention for its regulation of immunity and inflammation. Yet its role in toluene diisocyanate (TDI)-induced asthma still remains poorly characterized. In this study, mice were sens...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2015.08.1108
更新日期:2015-11-19 00:00:00
abstract::We have studied the effects of chronic slight to moderate lead exposure on the renin-angiotensin-aldosterone system in normotensive man. Plasma renin activity (PRA), blood angiotensin I (AI) concentration, angiotensin converting enzyme (ACE) activity and aldosterone concentration were measured in 33 normotensive men, ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(85)90096-7
更新日期:1985-04-01 00:00:00
abstract::A single s.c. injection of 60 mg/kg of monocrotaline to rats induced pulmonary alterations characterized by hyaline thrombi of capillaries and arterioles, focal necrosis of alveolar walls, and medial thickening and intimal hyalinosis of arteries. Such pathological alterations became apparent 7 days after injection and...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(84)90225-x
更新日期:1984-04-01 00:00:00
abstract::Betulinic acid (BA) is known to induce apoptosis in melanoma neuroectodermal and malignant brain cancer cell lines. Present report describes the role of antioxidants on the BA-induced toxicity to human cell line SK-N-MC. Hydrophilic antioxidants viz., L-ascorbic acid (VitC) and N-acetyl-L-cysteine (l-NAC) had no prote...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2004.03.027
更新日期:2004-11-02 00:00:00
abstract::A major public health concern is the degree to which environmental or occupational exposures to exogenous chemicals result in adverse health effects. Biological markers have the potential for helping to answer this important question by providing links between markers of exposures and markers of early stages of the de...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/0378-4274(95)03569-9
更新日期:1995-12-01 00:00:00
abstract::The effect of two polyamino-polycarboxylic acids, N-(2-hydroxyethyl) ethylenediamine triacetic acid (HEDTA) and diethylenetriamine penta-acetic acid (DTPA) and two thiol-chelating agents, sodium diethyldithiocarbamate (DDC) and dimercaptosuccinic acid (DMS) on the excretion of manganese (Mn) in rabbits given Mn i.p. w...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(80)90180-0
更新日期:1980-08-01 00:00:00
abstract::1. General anesthesia is achieved by anesthetic action in the central nervous system (CNS). 2. Whereas amnesia and unconsciousness are due to anesthetic action in the brain, recent evidence suggests that immobility in response to a noxious stimulus is achieved by anesthetic effects in the spinal cord. The putative spi...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/s0378-4274(98)00164-7
更新日期:1998-11-23 00:00:00
abstract::In the present study experiments are described, which indicate that the exposure of normal human skin fibroblasts (HSFs) to a low-frequency electromagnetic field of 20 Hz and 7-8 mT does induce terminal differentiation within 14 days of daily exposure of 12 h. As demonstrated by the analysis of the expression level of...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(98)00095-2
更新日期:1998-08-01 00:00:00
abstract::Traditional Chinese medicine (TCM) has become a crucial cause of drug-induced liver injury (DILI). Differ from chemical medicines, TCM feature more complex and mostly indefinite components. This review aimed to clarify the classification, underlying mechanisms and targets of the risk components in TCM-induced liver in...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/j.toxlet.2020.01.026
更新日期:2020-05-01 00:00:00
abstract::Nitrogen mustard (HN-2), also known as mechlorethamine, is an alkylating anticancer agent as well as blister inducing chemical warfare agent. We evaluated the cytoprotective efficacy of amifostine, DRDE-07 and their analogues, and other antidotes of mustard agents against HN-2. Administration of 1 LD(50) of HN-2 (20mg...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2009.04.015
更新日期:2009-08-10 00:00:00
abstract::Two groups, each of 4 rabbits, 17 and 4 months old, respectively, were given s.c. administrations of cadmium (Cd) at a dose level of 0.5 mg/kg/day 6 times per week for up to 32 weeks. In 17-month-old rabbits, low-molecular-weight proteinuria appeared in the 3rd week, proteinuria, glycosuria and anemia in the 6th week;...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(80)90123-x
更新日期:1980-09-01 00:00:00
abstract::Effects of sublethal concentration (0.8 of LC50 96 h) of nickel sulphate (NiSO4 X 7H2O) on muscle glycogen and blood lactic acid levels of a freshwater teleost, Colisa fasciatus, at time intervals from 3-96 h have been recorded. Muscle glycogen levels showed a general decrease at all time intervals compared with contr...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(84)90193-0
更新日期:1984-01-01 00:00:00
abstract::Environmental toxicants such as methylmercury play a critical role in the pathogenesis of many neurodevelopmental disorders. Environmental exposure to methylmercury frequently occurs at low doses, most frequently through fish consumption. Although the general population is at risk for exposure, pregnant women and youn...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/j.toxlet.2013.08.002
更新日期:2013-10-09 00:00:00
abstract::Elevated intracellular Ca(2+) content is implicated in ethanol-induced hepatocyte apoptosis and necrosis. Extracellular Ca(2+) influx has been suggested to play a role in this process. However, the exact Ca(2+)-permeable channel involved in the plasma membrane is still unclear. This study investigated the role of stor...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2011.11.007
更新日期:2012-02-05 00:00:00