Abstract:
:Aluminium (Al) oxyhydroxide (Alhydrogel®), the main adjuvant licensed for human and animal vaccines, consists of primary nanoparticles that spontaneously agglomerate. Concerns about its safety emerged following recognition of its unexpectedly long-lasting biopersistence within immune cells in some individuals, and reports of chronic fatigue syndrome, cognitive dysfunction, myalgia, dysautonomia and autoimmune/inflammatory features temporally linked to multiple Al-containing vaccine administrations. Mouse experiments have documented its capture and slow transportation by monocyte-lineage cells from the injected muscle to lymphoid organs and eventually the brain. The present study aimed at evaluating mouse brain function and Al concentration 180days after injection of various doses of Alhydrogel® (200, 400 and 800μg Al/kg of body weight) in the tibialis anterior muscle in adult female CD1 mice. Cognitive and motor performances were assessed by 8 validated tests, microglial activation by Iba-1 immunohistochemistry, and Al level by graphite furnace atomic absorption spectroscopy. An unusual neuro-toxicological pattern limited to a low dose of Alhydrogel® was observed. Neurobehavioural changes, including decreased activity levels and altered anxiety-like behaviour, were observed compared to controls in animals exposed to 200μg Al/kg but not at 400 and 800μg Al/kg. Consistently, microglial number appeared increased in the ventral forebrain of the 200μg Al/kg group. Cerebral Al levels were selectively increased in animals exposed to the lowest dose, while muscle granulomas had almost completely disappeared at 6 months in these animals. We conclude that Alhydrogel® injected at low dose in mouse muscle may selectively induce long-term Al cerebral accumulation and neurotoxic effects. To explain this unexpected result, an avenue that could be explored in the future relates to the adjuvant size since the injected suspensions corresponding to the lowest dose, but not to the highest doses, exclusively contained small agglomerates in the bacteria-size range known to favour capture and, presumably, transportation by monocyte-lineage cells. In any event, the view that Alhydrogel® neurotoxicity obeys "the dose makes the poison" rule of classical chemical toxicity appears overly simplistic.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Crépeaux G,Eidi H,David MO,Baba-Amer Y,Tzavara E,Giros B,Authier FJ,Exley C,Shaw CA,Cadusseau J,Gherardi RKdoi
10.1016/j.tox.2016.11.018subject
Has Abstractpub_date
2017-01-15 00:00:00pages
48-57eissn
0300-483Xissn
1879-3185pii
S0300-483X(16)30304-3journal_volume
375pub_type
杂志文章相关文献
TOXICOLOGY文献大全abstract::It is widely believed that the nigrostriatal toxicity of MPTP is due to its oxidation by brain monoamine oxidase first to MPDP+, and eventually to MPP+. Following uptake by the synaptic dopamine reuptake system, it is concentrated in the matrix of striatal mitochondria by an energy-dependent carrier, energized by the ...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/0300-483x(88)90169-2
更新日期:1988-04-01 00:00:00
abstract::Our previous study revealed that exposure to 0.4 ppm ozone (O(3)) enhanced nasal allergy-like reactions in guinea pigs. In the present study, we investigated the concentration-dependency of the effects of exposure to O(3) on the aggravation of nasal allergy-like reactions induced by repeated nasal administration of an...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2004.01.008
更新日期:2004-06-01 00:00:00
abstract::An embryotoxicity study on Ponceau 4 R was carried out in SPF Wistar rats. The substance was given by gavage from day 1 to 20 of the gestation period in doses of 0, 1000, 2000, and 4000 mg/kg bw per day, dissolved in distilled water. The foetuses were removed on day 21. No effect due to the treatment with the dye was ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(75)90117-1
更新日期:1975-11-01 00:00:00
abstract::The cytotoxicity and cardiotoxicity of benzoyl mustard (FCE 24517) and epoxamido (FCE 24561) synthetic derivatives of distamycin A were reported in the present study. The 50% inhibiting concentration (IC50) of colony formation of FCE 24517 on human SNB-19 glioblastoma, A2780 ovarian cancer and DU 145 prostate cancer w...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(92)90003-w
更新日期:1992-11-15 00:00:00
abstract::The lipid regulator gemfibrozil (GEM) is one of many human pharmaceuticals found in the aquatic environment. We previously demonstrated that GEM bioconcentrates in blood and reduces plasma testosterone levels in goldfish (Carassius auratus). In this study, we address the potential of an environmentally relevant waterb...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2006.08.025
更新日期:2006-12-07 00:00:00
abstract::Pulmonary fibrosis is one of the most common chronic interstitial lung diseases with high mortality rate after diagnosis and limited successful treatment. The present study was designed to assess the potential antifibrotic effect of thymoquinone (TQ) and whether TQ can attenuate the severity of oxidative stress and in...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2012.09.001
更新日期:2012-12-16 00:00:00
abstract::In the present study, we investigated the inducibility of the drug conjugate transporter genes MRP1 and MRP2 by redox-active compounds such as tertiary butylated hydroquinone (tBHQ) and quercetin and by chemicals known to activate the pregnane X receptor (PXR) such as rifampicin and clotrimazol and by the metalloid co...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(01)00570-4
更新日期:2002-02-28 00:00:00
abstract::Increasing experimental and clinical evidence suggest a contribution of non-drug related risk factors (e.g., underlying disease, bacterial/viral infection) to idiosyncratic drug reactions (IDR). Our previous work showed that co-treatment with bacterial endotoxin (LPS) and therapeutic doses of diclofenac (Dcl), an anal...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2015.03.004
更新日期:2015-05-04 00:00:00
abstract::Trans-1,2-dichloroethylene (t-DCE), an industrial solvent, proved to be moderately toxic when studied in small laboratory animals. In adult female rats brief (8 h) and prolonged (8 h daily, on 5 consecutive days a week, for more than 16 weeks) inhalation of 200 ppm--the current TLV/MAC in various countries--produced h...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(77)90059-2
更新日期:1977-04-01 00:00:00
abstract::The measurement of haemoglobin (Hb) adducts is an important tool for monitoring exposures to industrial chemicals such as ethylene, ethylene oxide and propylene oxide. The aim of the present study was to use this method to monitor occupational exposure to butadiene. The methodology was evaluated with Hb samples obtain...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(96)03435-x
更新日期:1996-10-28 00:00:00
abstract::To evaluate hydroperoxide generation as a potential mechanism of cyanide neurotoxicity, mice were treated with KCN (7 mg/kg, subcutaneously (s.c.)) and the level of lipid peroxidation (expressed as conjugated dienes) was measured later in various organs. Brain showed elevated conjugated diene levels after cyanide but ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(94)90221-6
更新日期:1994-04-18 00:00:00
abstract::The effect of dose and duration of treatment with chromium on its distribution in certain vital organs and the blood of rats has been investigated. The accumulation of metal was highest in liver and kidneys, followed by testes, brain and blood and was rather more dependent on the dose than on the duration of exposure....
journal_title:Toxicology
pub_type: 杂志文章
doi:
更新日期:1979-05-01 00:00:00
abstract::Human liver microsomes, supersomes from baculovirus-transformed insect cells expressing different human CYP450 isoforms, and control and CYP3A4 cDNA-transfected V79 Chinese hamster cells were tested for their ability to metabolize territrem B (TRB) and territrem C (TRC). Two TRB metabolites, designated MB(2) and MB(4)...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2005.10.010
更新日期:2006-02-01 00:00:00
abstract::One of the most sensitive and reproducible immunotoxic endpoints of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure is suppression of the antibody response to sheep red blood cells (SRBCs) in mice. Immunosuppression occurs in concert with hepatomegaly and associated induction of several hepatic cytochrome P450 enz...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2003.11.016
更新日期:2004-04-01 00:00:00
abstract::A flow-through rat tracheal implant system is described which permits the quantitative and repetitive exposure of respiratory epithelia to test gaseous substances. To investigate the acute toxicity of formaldehyde gas with this new system, open-ended rat tracheal implants were exposed to the gas for 1 h twice a week f...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(84)90142-2
更新日期:1984-04-16 00:00:00
abstract::Multidrug resistance type 1 P-glycoproteins (P-gp) and multidrug resistance associated proteins (MRP) were studied in differentiated primary human lung cells in culture, in comparison with permanent human lung cell lines and primary alveolar type II cells from rat lung. AII cells exhibited low basal levels of mdr1b mR...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(01)00458-9
更新日期:2001-10-05 00:00:00
abstract::Transgenic rat mutation assays can be used to assess genotoxic properties of chemicals in target organs for carcinogenicity. Mutations in transgenes are genetically neutral and accumulate during a treatment period; thus, assays are suitable for assessing the genotoxic risk of chemicals using a repeated-dose treatment ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2014.07.003
更新日期:2014-10-03 00:00:00
abstract::Heavy metals, such as iron and manganese, are involved in neurologic disease. Most often these diseases are associated with abnormal environmental exposures or abnormal accumulations of heavy metals in the body. There is increasing recognition that heavy metals normally present in the body also may play a role in dise...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/0300-483x(94)02962-t
更新日期:1995-03-31 00:00:00
abstract::The Salmonella mutagenicity assay was utilized to compare hepatic S9 fractions derived from wild and laboratory reared woodchucks (Marmota monax). Two promutagens, 7,12-dimethylbenz[a]anthracence (DMBA) and 2-amino-fluorene (AF) were tested at 5 concentrations with the tester strains TA98 and TA100, against 2 levels o...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(88)90058-3
更新日期:1988-01-01 00:00:00
abstract::Exposure to heavy metals contributes to most of the unexplained male infertility. Lead (Pb) is a well- known heavy metal, which disrupt the male reproductive system. This study was conducted to investigate the therapeutic and protective effects of green tea active principle, epigallocatechin gallate (EGCG), on the lea...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2019.04.015
更新日期:2019-06-15 00:00:00
abstract::Fenvalerate is a widely used synthetic pyrethroid insecticide and is reported to disrupt reproductive function in humans and animals. However, little is known about its influence on follicular development. In this study, rat preantral follicles were primary cultured to investigate the effects of fenvalerate on follicu...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2009.10.022
更新日期:2010-01-12 00:00:00
abstract::Age-related differences in susceptibility to cephaloridine nephrotoxicity were evaluated in male Fischer-344 rats. Rats, 2.5, 4, 10-12 and 27-29 months old, were administered a single intraperitoneal dose of cephaloridine and renal function evaluated 24 h later. Susceptibility to cephaloridine-induced nephrotoxicity w...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(86)90171-x
更新日期:1986-01-01 00:00:00
abstract::The effect of tamoxifen on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability has not been explored in corneal epithelial cells. This study examined whether tamoxifen altered [Ca2+]i and viability in SIRC corneal epithelial cells. Tamoxifen at concentrations > or = 1 microM increased [Ca2+]i in a concentration...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2008.10.001
更新日期:2009-01-08 00:00:00
abstract::Male Wistar rats injected i.p. with 30 mg Fe2+/kg body weight show hepatic damage as measured by an increase in lipid peroxides which correlated with elevated serum enzymes, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) and lactate dehydrogenase (LDH). Oral administration of spice principles, curc...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(95)03199-p
更新日期:1996-01-22 00:00:00
abstract::Cisplatin is used as a cytotoxic agent for the management of cervical cancer. However, the severity of the side-effects limits the use of this drug, particularly at high doses. Resistance to cisplatin is often attributed to a disruption in the normal apoptotic response via aberrant activation of pathways such as the m...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2015.07.010
更新日期:2015-09-01 00:00:00
abstract::Prenatal dexamethasone exposure (PDE) could induce testicular developmental toxicity in adults. The present study aims to confirm its intrauterine origination, and to explore its potential intrauterine programming mechanism. The pregnant rats were respectively injected subcutaneously with 0.2 and 0.8 mg/kg d dexametha...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2018.06.005
更新日期:2018-09-01 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::It is accepted practice in presenting organ weight data to express the results relative to the animal's body weight. The data presented suggest that in rats no benefits are obtained from this method either in reducing the variability of the data or in removing bias due to different body weights. By using simulated dat...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(76)90050-0
更新日期:1976-03-01 00:00:00
abstract::There are reports of alterations in the number and functions of the cells of the immune system in patients with metal-on-metal (MOM) orthopaedic implants. These effects have been correlated with elevated chromium levels in the patients' blood. We have investigated the interactions of clinically relevant concentrations...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2007.04.002
更新日期:2007-07-01 00:00:00
abstract::Pyrethroids are a class of insecticides involved in different neurological disorders. They cross the blood-brain barrier and exert their effect on dopaminergic system, contributing to the burden of oxidative stress in Parkinson's disease through several pathways. The aim of the present study was to evaluate the effect...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2006.10.015
更新日期:2007-01-18 00:00:00