Abstract：
:Aggregation of α-synuclein (α-syn) in the brain is a defining pathological feature of neurodegenerative disorders classified as synucleinopathies. They include Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Occupational and environmental exposure to manganese (Mn) is associated with a neurological syndrome consisting of psychiatric symptoms, cognitive impairment and parkinsonism. In this study, we examined α-syn immunoreactivity in the frontal cortex of Cynomolgus macaques as part of a multidisciplinary assessment of the neurological effects produced by exposure to moderate levels of Mn. We found increased α-syn-positive cells in the gray matter of Mn-exposed animals, typically observed in pyramidal and medium-sized neurons in deep cortical layers. Some of these neurons displayed loss of Nissl staining with α-syn-positive spherical aggregates. In the white matter we also observed α-syn-positive glial cells and in some cases α-syn-positive neurites. These findings suggest that Mn exposure promotes α-syn aggregation in neuronal and glial cells that may ultimately lead to degeneration in the frontal cortex gray and white matter. To our knowledge, this is the first report of Mn-induced neuronal and glial cell α-syn accumulation and aggregation in the frontal cortex of non-human primates.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Verina T,Schneider JS,Guilarte TRdoi
10.1016/j.toxlet.2012.12.006subject
Has Abstractpub_date
2013-03-13 00:00:00pages
177-83issue
3eissn
0378-4274issn
1879-3169pii
S0378-4274(12)01424-5journal_volume
217pub_type
杂志文章abstract：:The mammalian xenobiotic-metabolizing sulfotransferases are cytosolic enzymes, which form a gene superfamily (SULT). Ten distinct human SULT forms are known. Two SULT forms represent splice variants, the other forms are encoded by separate genes. Common functional polymorphisms of the transcribed region are known for ...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/s0378-4274(99)00214-3
更新日期：2000-03-15 00:00:00
abstract：:This study was designed to compare the pulmonary cellular proliferative effects of inhaled, size-separated preparations of chrysotile asbestos fibres with similar aerosol fibre concentrations of para-aramid fibrils. Following fibre preparation, rats were exposed for 2 weeks to aerosols of p-aramid fibrils or chrysotil...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(96)03751-4
更新日期：1996-11-01 00:00:00
abstract：:Children may be inherently more vulnerable than adults to the lethal effects associated with chemical warfare nerve agent (CWNA) exposure because of their closer proximity to the ground, smaller body mass, higher respiratory rate, increased skin permeability and immature metabolic systems. Unfortunately, there have on...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2015.11.023
更新日期：2016-01-22 00:00:00
abstract：:Hormonally active chemicals in the human diet, such as man-made estrogenic chemicals or plant-derived compounds (phytoestrogens), have become a matter of public concern. A significant part of human exposure to phytoestrogens is attributable to soy isoflavones. Besides their estrogenic properties, soy isoflavones also ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2004.04.005
更新日期：2004-06-15 00:00:00
abstract：:An in vivo intestinal perfusion technique was used to measure the absorption rates of five Cr compounds in black ducks. Cr was absorbed from saline solutions of KCr(SO4)2 and CrO3 at a rate about 1.5 to 2.0 times greater than from solutions of Cr, Cr(NO3)3, and Cr(C5H7O2)3. These results suggest the ionic form of Cr i...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(80)90191-5
更新日期：1980-08-01 00:00:00
abstract：:Activity of beta-glucuronidase and cathepsin-D were studied in brain, spinal cord and sciatic nerves of rats at 24 h or 10 days after daily i.p. administration of 50 mg/kg acrylamide. The activities of beta-glucuronidase and cathepsin-D in brain, spinal cord and sciatic nerves remained unaffected on single exposure bu...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(84)90068-7
更新日期：1984-08-01 00:00:00
abstract：:Troglitazone (TGZ) is an orally active hypoglycemic agent which is used for the treatment of non-insulin-dependent diabetes mellitus. It had been associated with severe drug-induced liver failure which resulted in its withdrawal from the market in 2000. While the exact mechanism of its toxicity remains unknown, it has...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2009.10.014
更新日期：2010-02-01 00:00:00
abstract：:Chemical-induced carcinogenesis has been in the focus of toxicological research for many decades. However, the mechanisms leading to tumor formation are only understood with certain substances. The intake of potential carcinogens by inhalation is a major route of exposure. Chemical-induced lung tumors are the final ma...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/s0378-4274(99)00285-4
更新日期：2000-03-15 00:00:00
abstract：:Alkyl hydroperoxide reductase 1 (Ahp1p) is a thioredoxin peroxidase of the peroxiredoxin family expressed by Saccharomyces cerevisiae. Recently, disruption of the AHP1 gene has shown that the gene is not essential for yeast growth on glucose medium but revealed a high sensitivity of null mutants to organic peroxides, ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(02)00280-1
更新日期：2002-10-05 00:00:00
abstract：:Male C57B1/6N mice, 8-10 weeks old were given a single oral dose of 0, 1.0 or 3.0 mg/kg body weight of trimethyltin hydroxide (TMT). Levels of ornithine decarboxylase (ODC) activity were measured in several brain areas, 1, 2 and 7 days later. The lower dose of TMT produced a decrease of ODC in the caudate nucleus and ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(87)90042-7
更新日期：1987-03-01 00:00:00
abstract：:Inflammation is one of the factors that may increase the sensitivity of hepatic cells to acetaminophen (APAP) induced toxicity. To investigate the mechanisms, we exposed 3-dimensional (3D) Human Liver Microtissues, a co-culture of primary human hepatocytes (PHH) and Kupffer cells (KCs), to 0, 0.5 (low), 5 (median) and...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2019.05.004
更新日期：2019-09-15 00:00:00
abstract：:Guidelines concerning the preclinical safety assessment of therapeutic proteins are available, e.g. in the European Community (EC Notes for Guidance). Unlike rather rigidly prescribing test systems such as those known for chemical substances, it is agreed that for biotechnologically-produced products, testing may be q...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(92)90206-y
更新日期：1992-12-01 00:00:00
abstract：:This study tested a hypothesis that soybean lipoxygenase (SLO), a model enzyme, may be capable of generating a glutathione (GSH) conjugate(s) from p-aminophenol (PAP). Horseradish peroxidase was employed as a positive control. GSH depletion or an increase in the absorption at 327 nm with time due to GS-PAP formation w...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(99)00188-5
更新日期：2000-01-05 00:00:00
abstract：:Effects of vitamin E on cell morphology and cellular protein thiols under oxidative stress was investigated in cultured rat hepatocytes with different vitamin E status. Hepatocytes were incubated in the presence or absence of 100 microM alpha-tocopherol succinate for 24 h then treated with 1.5 mM t-butyl hydroperoxide...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(96)03793-9
更新日期：1996-12-16 00:00:00
abstract：:There are reports of fluorochloridone (FLC)-induced male reproductive toxicity, but the underlying toxicological mechanisms remain unknown. In this study, we looked at how FLC exposure affected the integrity of the blood-testis barrier (BTB) and the Sertoli cell barrier and studied the molecular mechanisms. Male rats ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.07.001
更新日期：2018-10-01 00:00:00
abstract：:Olefinic hydrocarbons are metabolized in vivo by cytochrome P450-dependent monooxygenases to the corresponding epoxides. The maximum in vivo metabolic rate, which is an important toxicokinetic parameter, has been used to define the apparent rate constant (kapp) describing in vivo metabolic reactivity of alkenes. To de...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(94)03174-6
更新日期：1995-01-01 00:00:00
abstract：:Reactivity of phenoxyl radicals towards biomolecules (proteins, nucleic acids and lipids) is essential for antioxidant (protective) versus prooxidant (cytotoxic) effects of phenolic compounds (antioxidants, phytochemicals, environmental pollutants and toxic chemicals). The present study demonstrates for the first time...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(96)03767-8
更新日期：1996-10-01 00:00:00
abstract：:The target cell(s) of theobromine toxicity on rat testes and reproductive toxicity induced by pure theobromine and cocoa extract are evaluated in the present studies. Theobromine (500 mg/kg x 7 days) inhibited body weight gain in treated rats. Decreased cauda epididymal sperm reserve (38%), seminiferous tubule fluid (...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(94)90159-7
更新日期：1994-02-01 00:00:00
abstract：:Styrene-acrylonitrile trimer (SAN Trimer), a mixture of six isomers (four isomers of 4-cyano-1,2,3,4-tetrahydro-alpha-methyl-1-naphthaleneacetonitrile [THAN] and two isomers of 4-cyano-1,2,3,4-tetrahydro-1-naphthaleneproprionitrile [THNP]), is a by-product of a specific production process of styrene-acrylonitrile poly...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2008.01.016
更新日期：2008-04-21 00:00:00
abstract：:Dysglycemia and central nervous system (CNS) complications are the known adverse effects of fluoroquinolone antibiotics. Ciprofloxacin and levofloxacin are among the most prescribed antibiotics. In this study we demonstrate that ciprofloxacin and levofloxacin disturb glucose transport into HepG2 cells and such inhibit...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2008.10.017
更新日期：2009-01-30 00:00:00
abstract：:Acetylcholinesterase (AChE) inhibited by the organophosphorus nerve (OP) agent soman underlies a spontaneous and extremely rapid dealkylation ("aging") reaction which prevents reactivation by oximes. However, in vivo studies in various, soman poisoned animal species showed a therapeutic effect of oximes, with the exac...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2017.10.005
更新日期：2018-09-01 00:00:00
abstract：:The degradation of cyanogenic glycosides was studied in spontaneously fermenting cassava root pulp and in fresh pulp samples pretreated to prevent either endogenous beta-glycosidase activity, fermentation, or both. The rate of disappearance of the glycosides, as measured by hydrocyanic acid (HCN) production in situ, i...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(83)90153-4
更新日期：1983-03-01 00:00:00
abstract：:Short- and medium-term rodent bioassays have been proposed under ICH guidelines for use in testing for the carcinogenic potential of pharmaceuticals. Further evaluation of these models is needed urgently and coordinated efforts are in progress worldwide to expand the available database. Models currently being investig...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/s0378-4274(99)00227-1
更新日期：2000-03-15 00:00:00
abstract：:The exposure to cuprizone (CPZ) leads to demyelination in the central nervous system in rodents. To examine the developmental effects of CPZ exposure on hippocampal neurogenesis, pregnant rats were treated with 0, 0.1 or 0.4% CPZ in the diet from gestational day 6 to day 21 after delivery. On postnatal day 21, male of...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2015.01.022
更新日期：2015-05-05 00:00:00
abstract：:As a recreational drug of abuse and an injectable anesthetic, ketamine has been shown to cause cognitive dysfunction and induce psychotic states. Although the specific mechanism is still unclear, it may be linked to synaptic receptors, including the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2019.08.023
更新日期：2019-10-15 00:00:00
abstract：:This study aimed to evaluate bio-safety of magnetic chitosan nanogels as dual triggered drug carrier for doxorubicin through analysis of mitochondrial function. In the present study, chitosan/TPP nanogels containing magnetite nanoparticles (NPs) were prepared according to the ionotropic gelation method as novel pH-sen...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2017.06.004
更新日期：2017-08-15 00:00:00
abstract：:A low-Mr copper (Cu) and zinc (Zn)-binding protein was present in the liver of a control water lizard Triturus pyrrhogaster. Cadmium (Cd) accumulated in the liver of the animals after intramuscular injections of Cd salt and was bound to Cu- and Zn-binding protein of a single isoform that had properties characteristic ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(84)90203-0
更新日期：1984-05-01 00:00:00
abstract：INTRODUCTION:An increased health problem in industrialised countries is the contemporary concern of public and scientific community as well. This has been attributed in part to accumulated environmental pollutants especially radioactive substances and the use of nuclear power plants worldwide. However, the outcome of c...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2017.10.004
更新日期：2018-01-05 00:00:00
abstract：:Welding fumes contain various toxic metals including chromium (Cr), nickel (Ni) and manganese (Mn). An assessment of the risk to health of local and systemic exposure to welding fumes requires the assessment of both external and internal doses. The aims of this study were to test the relevance in small and medium size...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2014.09.008
更新日期：2014-12-01 00:00:00
abstract：:Isolated, perfused and ventilated guinea-pig lungs were exposed for 10 min to acid (sulphuric + nitric acid) aerosol mimicking acid rain at pH 4.5 or 2.5, as well as to a control distilled water aerosol (pH 6.0-6.5). Lung perfusing solution was recovered and thromboxane (TX) B2 and leukotriene (LT) B4 were measured by...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(87)90262-1
更新日期：1987-11-01 00:00:00
