Abstract:
:Gulf War Illness (GWI) affects 25% of veterans from the 1990-1991 Gulf War (GW) and is accompanied by damage to the brain regions involved in memory processing. After twenty-five years, the chronic pathobiology of GWI is still unexplained. To address this problem, we examined the long-term consequences of GW exposures in an established GWI mouse model to identify biological processes that are relevant to the chronic symptoms of GWI. Three-month old male C57BL6 mice were exposed for 10days to GW agents (pyridostigmine bromide and permethrin). Barnes Maze testing conducted at 15- and 16-months post-exposure revealed learning and memory impairment. Immunohistochemical analyses showed astroglia and microglia activation in the hippocampi of exposed mice. Proteomic studies identified perturbation of mitochondria function and metabolomics data showed decreases in the Krebs cycle compounds, lactate, β-hydroxybutyrate and glycerol-3 phosphate in the brains of exposed mice. Lipidomics data showed decreases in fatty acids, acylcarnitines and phospholipids, including cardiolipins in the brains of exposed mice. Pilot biomarker studies showed that plasma from exposed mice and veterans with GWI had increases in odd-chain, and decreases in long-chain, acylcarnitines compared to their respective controls. Very long-chain acylcarnitines were decreased in veterans with GWI compared to controls. These studies suggest that mitochondrial lipid disturbances might be associated with GWI and that further investigation is required to determine its role in the pathophysiology of this illness. Targeting mitochondrial function may provide effective therapies for GWI, and that lipid abnormalities could serve as biomarkers of GWI.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Abdullah L,Evans JE,Joshi U,Crynen G,Reed J,Mouzon B,Baumann S,Montague H,Zakirova Z,Emmerich T,Bachmeier C,Klimas N,Sullivan K,Mullan M,Ait-Ghezala G,Crawford Fdoi
10.1016/j.tox.2016.10.012subject
Has Abstractpub_date
2016-11-30 00:00:00pages
22-33eissn
0300-483Xissn
1879-3185pii
S0300-483X(16)30256-6journal_volume
372pub_type
杂志文章相关文献
TOXICOLOGY文献大全abstract::Clinical trials with antidotes are difficult to perform for a variety of practical, ethical, and financial reasons. As acute poisoning is a rare event, the commercial interest in basic and clinical research is low. Poisoned patients are usually not available for normal clinical trial procedures and, if they are, they ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2006.11.065
更新日期:2007-04-20 00:00:00
abstract::Dioxins, including the most toxic congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), exert diverse biological effects in humans and animals. Host resistance, especially to virus infections, is considered one of the most sensitive targets of TCDD-toxicity, while a recent study showed that the vulnerability to TCDD o...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(01)00535-2
更新日期:2002-01-15 00:00:00
abstract::Simple and efficient ex vivo/in vitro screening systems for contact allergens are developed for alternative to conventional animal tests. We have previously proposed an ex vivo/in vitro proliferation assay as a first stage screening method with advantages over existing alternatives, using lymph node cells (LNC) from s...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(96)89846-5
更新日期:1996-11-15 00:00:00
abstract::The effect of administration of a glutamate-containing protein hydrolysate on the arcuate nucleus of 10-day-old mice was studied by two methods. Arcuate nucleus damage resulted when administration was by a single large subcutaneous dose (100 ml/kg). When the same total dose was administered subcutaneously in five smal...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(75)90070-0
更新日期:1975-09-01 00:00:00
abstract::Acute toxic effects of the antineoplastic anthraquinones carminomycin, epirubicin, idarubicin and mitoxantrone were studied in primary cultures of cardiomyocytes, which were isolated from adult rats. Both time- and concentration-dependent changes of cell structure and viability (trypan blue exclusion) following incuba...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(99)00041-4
更新日期:1999-07-01 00:00:00
abstract::Metabonomics involves the application of advanced analytical tools to profile the diverse metabolic complement of a given biofluid or tissue. Subsequent statistical modelling of the complex multivariate spectral profiles enables discrimination between phenotypes of interest and identifies panels of discriminatory meta...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/j.tox.2010.07.022
更新日期:2010-12-30 00:00:00
abstract::Hyperhomocysteinemia has been proposed as an important risk factor for cardiac arrhythmias and ischemia worldwide. However, the cellular mechanism underlying toxic effects of homocysteine on hearts remains conjectural. It is well known that aberrant sodium channels can promote the development of cardiac arrhythmias an...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2008.11.020
更新日期:2009-02-27 00:00:00
abstract::Diesel exhaust particles (DEP) affect health adversely. Our previous studies revealed that DEP extracts up-regulated expression of genes related to drug metabolism, antioxidant enzymes, cell cycle/apoptosis and coagulation, and in addition, n-hexane soluble fraction (n-HSF) of DEP extracts contains aliphatic and polyc...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2009.05.012
更新日期:2009-07-28 00:00:00
abstract::Previous studies have shown that excess dietary Al during development can affect neurobehavioral measures and decrease tissue Mn of 21-day-old weanling mice without a corresponding increase in tissue Al concentrations. Al and Mn have similar tissue concentrations and similar affinities for transferrin, which is the ma...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(93)90154-k
更新日期:1993-07-11 00:00:00
abstract::Envenoming by the pitviper Bothrops jararacussu produces cardiovascular alterations, including coagulopathy, systemic hemorrhage, hypotension, circulatory shock and renal failure. In this work, we examined the activity of this venom in rat isolated right atria. Incubation with venom (0.025, 0.05, 0.1 and 0.2mg/ml) cau...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2014.06.010
更新日期:2014-09-02 00:00:00
abstract::Chlordecone (CD) impairs biliary excretion of organic anions (including phenolphthalein glucuronide (PG), imipramine polar metabolites, and taurocholate) without evidence of hepatocellular necrosis in rats. In this study we investigated the hypothesis that CD-induced hepatobiliary dysfunction is dependent on CD concen...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(94)90057-4
更新日期:1994-01-26 00:00:00
abstract::The current Organisation for Economic Co-operation and Development (OECD) guidelines for evaluating organophosphorus-induced delayed neuropathy (OPIDN) require the observation of dosed animals over several days and the sacrifice of 48 hens. Adhering to these protocols in tests with enantiomers is difficult because lar...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2011.12.004
更新日期:2012-02-26 00:00:00
abstract::Neonatal rat hearts were separated into separate cultures of beating myocytes (M cells), endothelial cells (E cells) and fibroblasts (F cells). Their susceptibilities to the toxic effects of emetine, chloroquine and metronidazole were then compared using a quantitative metabolic inhibition test (QMIT) and morphologic ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(84)90066-0
更新日期:1984-11-01 00:00:00
abstract::A clonal cell line, R40F, was selected from a heterogenous population of Cd2+ and Zn2+-resistant CHO-K1 cells. These R40F cells demonstrated resistance to 120- and 4-fold higher concentrations of Cd2+ and Zn2+, respectively, than did wild type CHO-K1 cells. When cultured in the presence of low concentrations of Cd2+ (...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(83)90088-4
更新日期:1983-03-01 00:00:00
abstract::The term "health/functional food" (HFF) refers to food supplements containing nutrients or other substances (in a concentrated form) that have a nutritional or physiological effect whose purpose is to supplement the normal diet. The Korean Health/Functional Food Act that came into effect in 2004 requires these product...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2006.01.016
更新日期:2006-04-03 00:00:00
abstract::The oxidation of guanine to 8-oxo-2'-deoxyguanosine (8-oxo-dG) is one of the most abundant and best studied oxidative DNA lesions and is commonly used as a biomarker for oxidative stress. Over the last decades, various methods for the detection of DNA oxidation products have been established and optimized. However, so...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2013.05.006
更新日期:2013-08-09 00:00:00
abstract::Exposure to low-dose benzene may lead to hematotoxicity and cause health problems. Though peripheral blood cell count is widely used in benzene exposure assessment and health risk assessment, the reports regarding the effects of low-dose benzene exposure on blood cell count remain inconsistent. To uncover more sensiti...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2018.09.004
更新日期:2018-12-01 00:00:00
abstract::A major goal in modern pharmacotechnology is to increase the therapeutic index of drugs by using nanoparticulate vehicle systems in order to ensure slow release or targeted delivery of drugs. With all great benefits, however, these innovative therapies can carry a risk for acute immune toxicity manifested in hypersens...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/j.tox.2005.07.023
更新日期:2005-12-15 00:00:00
abstract::It is well known that selenium is highly toxic to several species of mammals. Here we report the potential neurotoxicity of diselenides, as measured by the manifestation of seizures. The modulation of various neurotransmitter systems potentially involved in seizure episodes and death was also evaluated. The results of...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(02)00423-7
更新日期:2003-02-01 00:00:00
abstract::Mitochondrial fission, fusion, and mitophagy are interlinked processes that regulate mitochondrial shape, number, and size, as well as metabolic activity and stress response. The fundamental importance of these processes is evident in the fact that mutations in fission (DRP1), fusion (MFN2, OPA1), and mitophagy (PINK1...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2017.05.018
更新日期:2017-07-15 00:00:00
abstract::Leflunomide, used for the treatment of rheumatoid arthritis, has been reported to cause severe liver problems and liver failure; however, the underlying mechanisms are not clear. In this study, we used multiple approaches including genomic analysis to investigate and characterize the possible molecular mechanisms of t...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2017.10.002
更新日期:2017-12-01 00:00:00
abstract::The developing nervous system is susceptible to lead (Pb) exposure but less is known about the effect of this toxic agent in adult rat brain. Since astrocytes serve as a cellular Pb deposition site, it is of importance to investigate the response of astroglial cells in the adult rat brain in a model of acute lead expo...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(01)00415-2
更新日期:2001-08-28 00:00:00
abstract::Exposure of cultured rat mesangial cells to CdCl2 caused a dose- and time-dependent increase in intracellular glutathione that was significant at 0.5 microM and maximal at 1 microM Cd2+. The effect depended on glutathione synthesis and was masked by inhibiting synthesis with buthionine sulfoximine. The cells responded...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(93)90145-i
更新日期:1993-01-29 00:00:00
abstract::The effects of thallous cation (Tl(+)) on: (a) the production of oxidant species and (b) membrane fluidity were evaluated in human leukemia T cells (Jurkat). After 72 h of incubation in the presence of Tl(+) (5-100 microM), no significant changes in cell viability were observed, although the average cell size was decr...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2006.01.028
更新日期:2006-05-01 00:00:00
abstract::The standard treatment of poisoning by organophosphorus (OP) nerve agents with atropine and oximes is not sufficiently effective against all types of nerve agents. Alternative therapeutic strategies are required and bispyridinium non-oximes, acting as nicotinic antagonists, were identified as promising compounds. A pr...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2012.02.002
更新日期:2012-04-11 00:00:00
abstract::Inorganic arsenic (iAs) and its metabolites are transferred to the foetus through the placental barrier and this exposure can compromise the normal development of the unborn. For this reason, we assessed the toxicity of sodium arsenite (iAs(III)) and its metabolites dimethylarsinic acid (DMA(V)), monomethylarsonic aci...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2008.04.008
更新日期:2008-07-30 00:00:00
abstract::Some workers have suggested that 6 days xylitol administration to rats results in hepatic dysfunction. In our study xylitol was administered to rats by daily gastric intubation for a period of 14 days. Dose levels were 1.25, 2.5, 5 and 10 g/kg. During treatment (2, 5 and 14 days), animals were submitted to careful cli...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(77)90025-7
更新日期:1977-08-01 00:00:00
abstract::Cell cycle aberration was immunohistochemically examined in relation to preneoplastic liver cell foci expressing glutathione S-transferase placental form (GST-P) at early stages of tumor-promotion in rats with thioacetamide (TAA), a hepatocarcinogen facilitating liver cell regeneration. Immunoexpression of p16(Ink4a) ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2012.05.018
更新日期:2012-09-28 00:00:00
abstract::The effects of acute ethanol and acetaldehyde treatment on cell proliferation, cell adhesion capacity, neutral red incorporation into lysosomes, glutathione content, protein sulfhydryl compounds, lipid peroxidation, inner mitochondrial membrane integrity (MTT test), lactate dehydrogenase activity (LDH) and ultrastruct...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(97)03650-0
更新日期:1997-06-27 00:00:00
abstract::The ability of urban oxidant and acid air pollutants to induce heat shock proteins (HSPs) in the mammalian lung is not known. Such proteins are known to be correlated with environmental stress and pathophysiological conditions. In this study, stress-inducible HSP 70 was assessed by slot-blotting in rat lungs (N=10 per...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(95)03250-j
更新日期:1996-02-22 00:00:00