Abstract:
:Mercury (Hg) has long been recognized as a neurotoxicant; however, recent work in animal models has implicated Hg as an immunotoxicant. In particular, Hg has been shown to induce autoimmune disease in susceptible animals with effects including overproduction of specific autoantibodies and pathophysiologic signs of lupus-like disease. However, these effects are only observed at high doses of Hg that are above the levels to which humans would be exposed through contaminated fish consumption. While there is presently no evidence to suggest that Hg induces frank autoimmune disease in humans, a recent epidemiological study has demonstrated a link between occupational Hg exposure and lupus. In our studies, we have tested the hypothesis that Hg does not cause autoimmune disease directly, but rather that it may interact with triggering events, such as genetic predisposition, exposure to antigens, or infection, to exacerbate disease. Treatment of mice that are not susceptible to Hg-induced autoimmune disease with very low doses and short term exposures of inorganic Hg (20-200 microg/kg) exacerbates disease and accelerates mortality in the graft versus host disease model of chronic lupus in C57Bl/6 x DBA/2 mice. Furthermore, low dose Hg exposure increases the severity and prevalence of experimental autoimmune myocarditis (induced by immunization with cardiac myosin peptide in adjuvant) in A/J mice. To test our hypothesis further, we examined sera from Amazonian populations exposed to Hg through small-scale gold mining, with and without current or past malaria infection. We found significantly increased prevalence of antinuclear and antinucleolar antibodies and a positive interaction between Hg and malaria. These results suggest a new model for Hg immunotoxicity, as a co-factor in autoimmune disease, increasing the risks and severity of clinical disease in the presence of other triggering events, either genetic or acquired.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Silbergeld EK,Silva IA,Nyland JFdoi
10.1016/j.taap.2004.11.035subject
Has Abstractpub_date
2005-09-01 00:00:00pages
282-92issue
2 Suppleissn
0041-008Xissn
1096-0333pii
S0041-008X(05)00324-8journal_volume
207pub_type
杂志文章,评审abstract::Low dietary concentrations of methionine and cysteine are known to decrease hepatic glutathione content. However, it is not known if restricting the dietary content of these sulfur containing amino acids also affects hepatic levels of adenosine 3'-phosphate 5'-phosphosulfate (PAPS), the cofactor for sulfation, or meta...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90025-p
更新日期:1990-02-01 00:00:00
abstract::2,3- and 3,4-Dichlorophenyl methyl sulfoxides and 2,3- and 3,4-dichlorophenyl methyl sulfones (2,3- and 3,4-DCPSO2Mes) were detected in the urine of rats administered o-dichlorobenzene (o-DCB). After administration of o-DCB to rats, swift decreases were observed in the concentrations of o-DCB in blood, liver, and kidn...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8191
更新日期:1997-08-01 00:00:00
abstract::Nonmelanoma skin cancer is the most common cancer among humans and solar UV radiation, particularly its UVB component (290-320 nm), is its major cause. One way to reduce the occurrence of the cancer is via the use of substances (often antioxidants) termed "photochemopreventive agents". Resveratrol (trans-3,4',5-trihyd...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/s0041-008x(02)00014-5
更新日期:2003-01-01 00:00:00
abstract::Many studies of nanomaterials make non-systematic alterations of nanoparticle physicochemical properties. Given the immense size of the property space for nanomaterials, such approaches are not very useful in elucidating fundamental relationships between inherent physicochemical properties of these materials and their...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2017.03.011
更新日期:2017-05-15 00:00:00
abstract::6-Hydroxy-trans,trans-2,4-hexadienal (CHO-M-OH) is a metabolite of trans,trans-muconaldehyde (muconaldehyde or MUC), a microsomal hematotoxic ring-opened metabolite of benzene. In the present study, the toxicity of CHO-M-OH was examined. In order to assess potential toxic effects of CHO-M-OH on the maturation of eryth...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1995.1101
更新日期:1995-06-01 00:00:00
abstract::The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effec...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.08.024
更新日期:2013-11-15 00:00:00
abstract::The industrial solvent ethylene glycol monomethyl ether (EGME) is a known teratogen that has been reported to alter calcium metabolism in guinea pigs during chronic exposure. Because of the tremendous demand of reproduction on maternal calcium stores, the effects of EGME on calcium and vitamin D metabolism during gest...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(86)90050-5
更新日期:1986-11-01 00:00:00
abstract::The physiologically based dosimetry description for acrylonitrile (ACN) and its mutagenic epoxide metabolite 2-cyanoethylene oxide (CEO) in F-344 rats (M. L. Gargas, M. E. Anderson, S.K.O. Teo, R. Batra, T. R. Fennell, and G. L. Kedderis, 1995, Toxicol. Appl. Pharmacol. 134, 185-194) has been refined to include a phys...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.0239
更新日期:1996-10-01 00:00:00
abstract::Azole derivatives are teratogenic in rats and mice in vitro and in vivo. The postulated mechanism for the dysmorphogenetic effects is the inhibition of retinoic acid (RA)-degrading enzyme CYP26. Azole-related abnormalities are confined to structures controlled by RA, especially the neural crest cells, hindbrain, crani...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.09.025
更新日期:2009-01-01 00:00:00
abstract::Although the precise etiology of Rheumatoid arthritis (RA) remains obscure, heightened immune response is thought to play a vital role in provoking joint inflammation and bone erosion. This study aims at comparatively evaluating the effects of two monoclonal antibodies Ranibizumab (RANI) as anti-VEGF antibody and Toci...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2018.07.014
更新日期:2018-10-01 00:00:00
abstract::We use a stochastic model describing initiation and clonal growth of altered cells to analyze data from an initiation-promotion hepatocarcinogenesis experiment in female Wistar rats. Starting at 7 weeks of age, the animals were treated for 10 days with the initiating agent diethylnitrosamine (DEN, 10 mg/kg body wt per...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2000.8980
更新日期:2000-08-15 00:00:00
abstract::Tongue cancer is one of the most common oral malignancies. Quisinostat is a histone deacetylase inhibitor with antitumor activity. The aim of this study was to evaluate the effects of quisinostat on the viability of tongue squamous cell carcinoma (TSCC) cells (CAL-27, TCA-8113) in vitro and in vivo. Cell viability, ce...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2020.115363
更新日期:2021-01-01 00:00:00
abstract::This study is aimed at the development of a cell culture assay which may supplement or replace the animal Draize skin irritancy test. Using human keratinocytes, the measurement of proinflammatory eicosanoid and interleukin-1 alpha release and of the impairment of cell viability have provided a suitable in vitro/in viv...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1994.1144
更新日期:1994-07-01 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::To further elucidate the mechanism of cadmium inhibition of renal amino acid transport, brush border membrane vesicles were isolated from rabbit renal cortex and the effect of cadmium on the uptake of L-glutamate into the vesicles was investigated. Preincubation of the membranes with CdCl2 decreased sodium-dependent L...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1995.1226
更新日期:1995-12-01 00:00:00
abstract::Pyrrolizidine alkaloids (PAs) are a group of hepatic toxicant widely present in plants. Cytochrome P450 (CYP) 3A plays a key role in metabolic activation of PAs to generate electrophilic metabolites, which is the main cause of hepatotoxicity. We have previously demonstrated the sex difference in developmental toxicity...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2020.115137
更新日期:2020-11-01 00:00:00
abstract::This study investigated the in vivo metabolism of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP) in rats after multiple dosing, the metabolism of MEHP in primary rat hepatocyte cultures for periods of up to 3 days, and the biotransformation of some major metabolites of MEHP. Rats were orally...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(85)90096-1
更新日期:1985-08-01 00:00:00
abstract::Many environmental contaminants can disrupt the adaptive immune response. Exposure to the ubiquitous aryl hydrocarbon receptor (AhR) ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other agonists suppresses the antibody response. The underlying pathway mechanism by which TCDD alters B cell function is not well u...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.01.015
更新日期:2013-04-01 00:00:00
abstract::Epidemiological studies have shown an association between elevated levels of particulate matter air pollution and increased morbidity and hospital visits in asthmatics. Residual oil fly ash (ROFA) is a primary combustion particle containing sulfate and metals such as vanadium, nickel, and iron. In this study the effec...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1999.8709
更新日期:1999-08-01 00:00:00
abstract::The toxic milk mutation is an autosomal recessive mutation found in an inbred C57BL/6J strain of mice which results in an excessive hepatic accumulation of copper (Cu), mostly associated with metallothionein (MT). The possible toxicological significance of elevated levels of hepatic copper-metallothionein (Cu-MT) was ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1994.1052
更新日期:1994-03-01 00:00:00
abstract::Di-Calciphor is a synthetic derivative of prostaglandin B1 that protects against cerebral and cardiac ischemia apparently by preserving mitochondrial function. To determine whether di-Calciphor specifically protects against mitochondrial failure, we studied its effects on mitochondrial functions in hepatocytes treated...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1994.1087
更新日期:1994-05-01 00:00:00
abstract::According to the advocated paradigm shift in toxicology, acquisition of knowledge on the mechanisms underlying the toxicity of chemicals, such as perturbations of biological pathways, is of primary interest. Pluripotent stem cells (PSCs), such as human embryonic stem cells (hESCs) and human induced pluripotent stem ce...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2014.08.007
更新日期:2014-10-15 00:00:00
abstract::Dantrolene is an effective antagonist of anesthesia-induced malignant hyperthermia due to a poorly understood action on skeletal muscle. The present study examines whether the red blood cell can be used as a model to investigate the mechanism of dantrolene action. Halothane (4.7 mM) caused 9% hemolysis of red blood ce...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90133-5
更新日期:1987-09-30 00:00:00
abstract::Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the ne...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2015.12.012
更新日期:2016-01-15 00:00:00
abstract::Guttiferone-A (GA) is a natural occurring polyisoprenylated benzophenone with cytotoxic action in vitro and anti-tumor action in rodent models. We addressed a potential involvement of mitochondria in GA toxicity (1-25 μM) toward cancer cells by employing both hepatic carcinoma (HepG2) cells and succinate-energized mit...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.04.011
更新日期:2011-06-15 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
abstract::Previous work has shown that chlordecone (CD)-amplified CCl4 hepatotoxicity and lethality can be mitigated by pretreatment with cyanidanol. These studies also revealed that stimulated hepatocellular regeneration might play an important role in the cyanidanol protection of CD-amplified CCl4 toxicity. The present studie...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(91)90268-j
更新日期:1991-03-15 00:00:00
abstract::Recently, Gray and Ostby (Toxicol. Appl. Pharmacol. 133, 285-294, 1995) reported that in utero and lactational TCDD exposure causes striking abnormalities in the rat female reproductive system, including reduced fecundity and vaginal threads. The mechanism by which TCDD induces such abnormalities is unknown. Thus, we ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8295
更新日期:1997-12-01 00:00:00
abstract::The cardiotoxicity caused by doxorubicin and extravasation injury caused by anthracyclines is reduced by the clinically approved bisdioxopiperazine drug dexrazoxane. Dexrazoxane is a rings-closed analog of EDTA and is hydrolyzed in vivo to a form that strongly binds iron. Its protective effects were originally thought...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2020.115038
更新日期:2020-07-15 00:00:00
abstract::The Bcl-2 family contains a panel of proteins which are conserved regulators of apoptosis in mammalian cells, like the anti-apoptotic protein Bcl-2. According to its significant role in altering susceptibility to apoptosis, the deciphering of the mechanism of Bcl-2 expression modulation may be crucial for identifying ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.07.010
更新日期:2011-10-01 00:00:00