Abstract:
:Acetylcholine and other neurotransmitters play unique trophic roles in brain development. Accordingly, drugs and environmental toxicants that promote or interfere with neurotransmitter function evoke neurodevelopmental abnormalities by disrupting the timing or intensity of neurotrophic actions. The current review discusses three exposure scenarios involving acetylcholine systems: nicotine from maternal smoking during pregnancy, exposure to environmental tobacco smoke (ETS), and exposure to the organophosphate insecticide, chlorpyrifos (CPF). All three have long-term, adverse effects on specific processes involved in brain cell replication and differentiation, synaptic development and function, and ultimately behavioral performance. Many of these effects can be traced to the sequence of cellular events surrounding the trophic role of acetylcholine acting on its specific cellular receptors and associated signaling cascades. However, for chlorpyrifos, additional noncholinergic mechanisms appear to be critical in establishing the period of developmental vulnerability, the sites and type of neural damage, and the eventual outcome. New findings indicate that developmental neurotoxicity extends to late phases of brain maturation including adolescence. Novel in vitro and in vivo exposure models are being developed to uncover heretofore unsuspected mechanisms and targets for developmental neurotoxicants.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Slotkin TAdoi
10.1016/j.taap.2003.06.001subject
Has Abstractpub_date
2004-07-15 00:00:00pages
132-51issue
2eissn
0041-008Xissn
1096-0333pii
S0041008X04000456journal_volume
198pub_type
杂志文章,评审abstract::Melittin is a cationic, hemolytic peptide that is the main toxic component in the venom of the honey bee (Apis mellifera). Melittin has multiple effects, including anti-bacterial, anti-viral and anti-inflammatory, in various cell types. However, the anti-apoptotic mechanisms of melittin have not been fully elucidated ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.08.012
更新日期:2011-10-15 00:00:00
abstract::Previous experiments showed that treatment of mice and rats with thioacetamide (TAA) induced liver cell damage, fibrosis and/or cirrhosis, associated with increased oxidative stress and activation of hepatic stellate cells. Some experiments suggest that CYP2E1 may be involved in the metabolic activation of TAA. Howeve...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2007.11.010
更新日期:2008-05-01 00:00:00
abstract::In the present study the promoting activity of various PCB and PBB isomers and congeners in rat liver has been studied and compared with a variety of primary xenobiotic-mediated enzymatic changes in this target organ. Female Wistar rats were given diethylnitrosamine (DEN; 10 mg/kg body wt for 10 days) and were subsequ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(91)90250-i
更新日期:1991-12-01 00:00:00
abstract::Neuropathy target esterase (NTE) is a membrane-bound protein with high esterase catalytic activity. The physiological function of the protein is not known and the catalytic activity is not essential to health of nerve axons. Nevertheless there is overwhelming evidence that modification of the structure of NTE by coval...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/0041-008x(90)90036-t
更新日期:1990-03-01 00:00:00
abstract::A series of psychopharmacological agents were administered to adult male Fischer-344 rats pretreated with a tremorigenic dose of chlordecone in an attempt to elucidate the involvement of spinal and supraspinal processes in the mediation and/or expression of chlordecone-induced tremor. Agents effective in attenuating t...
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
abstract::Polychlorinatedbiphenyls (PCBs) are a group of persistent and widely dispersed environmental pollutants, some of which may be immunotoxic. In the present study, we investigated the effect of PCBs on immune system by assessing apoptotic cell death in human monocytic U937 cells. Among the various congeners tested, 2,2',...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2000.9034
更新日期:2000-11-15 00:00:00
abstract::Statins are widely used to treat lipid disorders. These drugs are safe and well tolerated; however, in <1% of patients, myopathy and/or rhabdomyolysis can develop. To better understand the mechanism of statin-induced myopathy, we examined the ability of structurally distinct statins to induce apoptosis in an optimized...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2004.04.010
更新日期:2004-11-01 00:00:00
abstract::Organophosphorus-ester induced delayed neurotoxicity (OPIDN) is a neurodegenerative disorder characterized by ataxia progressing to paralysis with a concomitant central and peripheral, distal axonapathy. Diisopropylphosphorofluoridate (DFP) produces OPIDN in the chicken that results in mild ataxia in 7-14 days and sev...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.07.017
更新日期:2011-11-01 00:00:00
abstract::Nitrogen mustard is a vesicant that causes damage to the respiratory tract. In these studies, we characterized the acute effects of nitrogen mustard on lung structure, inflammatory mediator expression, and pulmonary function, with the goal of identifying mediators potentially involved in toxicity. Treatment of rats (m...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2010.09.016
更新日期:2011-01-01 00:00:00
abstract::Corticosteroids will induce cleft palate in mice. One suggested mechanism for this effect is through inhibition of phospholipase activity. This hypothesis was tested by measuring the effects of dexamethasone, a synthetic corticosteroid, on phospholipase activity in cultures of palate mesenchymal cells. Palate mesenchy...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90207-2
更新日期:1984-09-15 00:00:00
abstract::This study investigated the protective effects of curcumin on tetrachloro-p-benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cel...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2014.08.003
更新日期:2014-10-15 00:00:00
abstract::The benzofurane derivative benzbromarone (BBR) previously has led to liver tumor formation after long-term treatment of rats, but no indications of genotoxicity were detected. The present studies were designed to elucidate the mechanism(s) possibly involved in liver tumor formation by BBR. Female Wistar rats were used...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90343-s
更新日期:1990-12-01 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
abstract::Cadmium chloride (CdCl2) at a dose of 1 mg/kg of body weight was injected into male Wistar rats twice a day (12-hr intervals) for 7 consecutive days. A group of treated rats was maintained without any treatment for an additional period of 10 days and killed on the following day (on Day 18). Plasma aldosterone concentr...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90346-6
更新日期:1984-12-01 00:00:00
abstract:UNLABELLED:In the heart, cardiac fibroblasts (CF) and cardiac myofibroblasts (CMF) are the main cells responsible for wound healing after cardiac insult. Exchange protein activated by cAMP (EPAC) is a downstream effector of cAMP, and it has been not completely studied on CF. Moreover, in CMF, which are the main cells r...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.06.022
更新日期:2013-10-15 00:00:00
abstract::Hepatotoxic doses of acetaminophen cause widespread alkylation of liver and early loss of cytosolic Ca2+ regulation. Although the precise location and target of lethal alkylation are not known, Ca2+ accumulation is viewed as a possible link between cell alkylation and cell death. We have recently shown that Ca2+ accum...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(91)90028-d
更新日期:1991-11-01 00:00:00
abstract::The relationship of exposure and tissue concentration of parent chemical and metabolites over prolonged exposure is a critical issue for chronic toxicities mediated by metabolite(s) rather than parent chemical alone. This is an issue for AsV because its trivalent metabolites have unique toxicities and relatively great...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.07.018
更新日期:2008-11-01 00:00:00
abstract::Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current tre...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2007.01.030
更新日期:2007-11-01 00:00:00
abstract::2,5-Hexanedione (HD) produces a neurofilamentous axonpathy in humans and experimental animals. The present study was carried out to determine the time course of the effects of HD on muscle spindle position sensitivity to permit comparisons with similar effects of other toxicants which produce a neurofilamentous axonop...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90235-m
更新日期:1990-04-01 00:00:00
abstract::Morphine has been shown to reduce renal and hepatic clearance of several xenobiotics in rodents. After iv administration of gentamicin, 10 to 30 mg/kg, its plasma levels were elevated in mice given morphine, 20 mg/kg sc. Plasma clearance of gentamicin was nearly halved by morphine, due primarily to lowering of the eli...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(88)90044-0
更新日期:1988-05-01 00:00:00
abstract::Propanil, 3,4-dichloropropionanilide, a commonly used herbicide, has been shown to induce effects on the mouse immune system. The aim of this study was to assess the immunotoxicity of propanil in occupationally exposed agricultural workers and to characterize its molecular mechanism of action. Seven agricultural worke...
journal_title:Toxicology and applied pharmacology
pub_type: 临床试验,杂志文章
doi:10.1016/j.taap.2007.04.017
更新日期:2007-07-15 00:00:00
abstract::We evaluated the inhibition of striatal cholinesterase activity following intracerebral administration of paraoxon assaying activity either in tissue homogenates ex vivo or by substrate hydrolysis in situ. Artificial cerebrospinal fluid (aCSF) or paraoxon in aCSF was infused unilaterally (0.5 microl/min for 2 h) and i...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2009.02.022
更新日期:2009-05-01 00:00:00
abstract::A cadmium-binding substance with a molecular weight even lower than that of metallothionein was demonstrated on Sephadex G-75 gel filtration chromatography of the soluble fractions from newborn human and adult rat liver homogenates and adult human hemolysate which were mixed with CdCl2 in vitro. This substance was pur...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90057-7
更新日期:1984-03-30 00:00:00
abstract::Natural flavonoids have diverse pharmacological activities, including anti-oxidative, anti-inflammatory, and anti-cancer activities. In this study, we investigated the molecular mechanism underlying the action of 5-methoxyflavanone (5-MF) which has a strong bioavailability and metabolic stability. Our results show tha...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.05.003
更新日期:2011-08-01 00:00:00
abstract::After a fire involving a transformer, the State Office Building in Binghamton, New York, was contaminated with soot containing polychlorinated biphenyls, biphenylenes, naphthalenes, dioxins, and dibenzofurans. The toxicity of the soot and its effect on liver morphology after prolonged (subchronic) exposure were determ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90099-1
更新日期:1984-05-01 00:00:00
abstract::Niclosamide is an antihelminthic drug used worldwide for the treatment of tapeworm infections. Recent drug repurposing screens have highlighted the broad bioactivity of niclosamide across diverse mechanisms of action. As a result, niclosamide is being evaluated for a range of alternative drug-repurposing applications,...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2019.114699
更新日期:2019-10-01 00:00:00
abstract::Three major enzyme systems have been shown to metabolize epoxidized xenobiotics in vertebrate tissues, and this study demonstrates that these enzyme systems can be differentially induced. The cytosolic epoxide hydrolase activity was routinely monitored with trans-beta-ethylstyrene oxide, the microsomal epoxide hydrola...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(83)90342-3
更新日期:1983-11-01 00:00:00
abstract::A pressing need exists to develop and validate molecular biomarkers to assess the early effects of chemical agents, both individually and in mixtures. This is particularly true for new and chemically intensive industries such as the semiconductor industry. Previous studies from this laboratory and others have demonstr...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2005.01.020
更新日期:2005-08-07 00:00:00
abstract::Polybrominated diphenyl ethers (PBDEs) have been used in a wide variety of consumer applications as additive flame retardants. In North America, scientists have noted continuing increases in the levels of PBDE congeners measured in human serum. Some recent studies have found that PBDEs are associated with adverse heal...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.09.007
更新日期:2013-12-01 00:00:00
abstract::Staphylococcal enterotoxin C2 (SEC2), a member of bacterial superantigen, is one of the most potent known activators of T lymphocytes. With this property, SEC2 has already been used in clinic as a tumor immunotherapy agent in China. To increase the antitumor activity, a SEC2 mutant named ST-4 (GKVTG102-106WWH) with am...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.10.009
更新日期:2016-12-15 00:00:00