MeHg-induced encephalopathy
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE1075 | GEO | 2004/03/11
SECONDARY ACCESSION(S): PRJNA87171
REPOSITORIES: GEO
Similar Datasets
Project description:In this dose series pregnant CD-1 (outbred) dams were exposed to the 2-chloro analogue of 2'-deoxyadenosine (a metabolic toxin) on 8 d.p.c. Test doses were developed from a teratological series for 2CdA-induced microphthalmia using BMDS modeling software from the US EPA. Benchmark doses for microarray analysis were: 5.0 mg/kg (25% risk), 2.5 mg/kg (5% risk), 1.25 mg/kg (NOAEL), and 0.625 mg/kg (subNOAEL). All measurements were on RNA from the embryo proper at 3.0h post-treatment. Keywords = dose series Keywords = 2-chloro-2'deoxyadenosine Keywords = embryo Keywords = microphthalmia Keywords: dose response
2004-03-11 | GSE1068 | GEO
Project description:In this time course pregnant CD-1 (outbred) dams were exposed to MeHg as monomethylmercuric chloride intraperitoneally on 9 d.p.c. The test dose of 5.0 mg/kg MeHg was selected as a dose with an estimated 20% increased risk for encephalopathy in term fetuses, with no evidence of maternal toxicosis. Exposed embryos were co-treated with PK11195, a nontoxic ligand of the mitochondrial peripheral-type benzodiazepine receptor (Bzrp) that effectively suppresses developmental toxicity induced with MeHg. The anticipated remediation with 5.0 mg/kg and 4.0 mg/kg PK11195 is <10% malformations. Sampling intervals ranged from 3.0h to 6.0h post-exposure. All measurements were on RNA from the embryonic forebrain (prosencephalon). Keywords = time series Keywords = mercury Keywords = PK11195 Keywords = embryo Keywords = Fetal Minamata Disease Keywords: time-course
2004-03-11 | GSE1077 | GEO
Project description:This series compares the effects that two pharmacologically distinct ligands at the mitochondrial peripheral-type benzodiazepine receptor (Bzrp). PK11195 (4.0 mg/kg, a presumed antagonist) has no observable adverse effects in pregnant mice on either 8 days post-coitus (d.p.c.) or 9 d.p.c. Furthermore, PK11195 is shown to rescue mouse fetuses from microphthalmia or microphthalmia-microcephaly induced with 2CdA or MeHg, respectively; effects of PK11195 on EtOH-induced craniofacial malformations are not yet unkown. Ro5-4864 (4.0 mg/kg, a presumed agonist) is weakly teratogenic on 8 d.p.c. (effects on 9 d.p.c. unknown) and this Bzrp ligand does not rescue fetuses from malformations induced with either 2CdA or MeHg; effects of Ro5-4864 on EtOH-induced craniofacial malformations is unknown for either sensitive (C57BL/6J) or insensitive (C57BL/6N) strains. The 4.0 mg/kg dose of Bzrp ligands is consistent with pharmacological activity in several studies. Pregnant mice were exposed to these agents on 8 d.p.c. (2CdA, EtOH) or 9 d.p.c. (MeHg). The test dose of 2.5 mg/kg 2CdA was modeled for a 5% increased risk of microphthalmia in term fetuses. Full remediation with PK11195 anticipated. The test dose of 5.0 mg/kg MeHg gives an estimated 20% increased risk of microphthalmia-microcephaly (encephalopathy) in term fetuses. Partial remediation with PK11195 is anticipated to <10% malformations. Again the effects of PK11195 on EtOH teratogenicity is not yet known. The sampling time was chosen as the time of p53 protein induction (3.0h to 4.5h post-treatment). Whereas co-treatment with PK11195 suppresses embryonic p53 protein induction Ro5-4864 does not block this reaction. All measurements were on RNA from the embryonic headfold (8 d.p.c.) or prosencephalon (9 d.p.c.). Keywords = peripheral benzodiazepine receptor Keywords = Bzrp ligands Keywords = PK11195 Keywords = Ro5-4864 Keywords = embryo Keywords = p53 protein induction
2010-06-09 | E-GEOD-1072 | biostudies-arrayexpress
Project description:With the advent of high information content technologies, especially microarrays, it is pertinent to determine the impact of molecular data on the NOAELs. Consequently, we conducted an integrative study to identify a no transcriptomic effect dose using microarray analyses coupled with qPCR and determined how this correlated with the NOAEL. We assessed the testicular effects of the antiandrogen, flutamide (FM), in a rat 28-day toxicity study using doses of 0.2-30 mg/kg/day. Concerning molecular data, we observed differential gene expression starting from 1 mg/kg/day and a deregulation of more than 1500 genes at 30 mg/kg/day. Dose-related changes were identified for the major pathways associated with the testicular lesion (eg fatty acid metabolism), that were confirmed by qPCR. These data, along with standard measurements supported the no effect dose of 0.2 mg/kg/day.
2011-03-29 | GSE28202 | GEO
Project description:This series compares the effects that two pharmacologically distinct ligands at the mitochondrial peripheral-type benzodiazepine receptor (Bzrp). PK11195 (4.0 mg/kg, a presumed antagonist) has no observable adverse effects in pregnant mice on either 8 days post-coitus (d.p.c.) or 9 d.p.c. Furthermore, PK11195 is shown to rescue mouse fetuses from microphthalmia or microphthalmia-microcephaly induced with 2CdA or MeHg, respectively; effects of PK11195 on EtOH-induced craniofacial malformations are not yet unkown. Ro5-4864 (4.0 mg/kg, a presumed agonist) is weakly teratogenic on 8 d.p.c. (effects on 9 d.p.c. unknown) and this Bzrp ligand does not rescue fetuses from malformations induced with either 2CdA or MeHg; effects of Ro5-4864 on EtOH-induced craniofacial malformations is unknown for either sensitive (C57BL/6J) or insensitive (C57BL/6N) strains. The 4.0 mg/kg dose of Bzrp ligands is consistent with pharmacological activity in several studies. Pregnant mice were exposed to these agents on 8 d.p.c. (2CdA, EtOH) or 9 d.p.c. (MeHg). The test dose of 2.5 mg/kg 2CdA was modeled for a 5% increased risk of microphthalmia in term fetuses. Full remediation with PK11195 anticipated. The test dose of 5.0 mg/kg MeHg gives an estimated 20% increased risk of microphthalmia-microcephaly (encephalopathy) in term fetuses. Partial remediation with PK11195 is anticipated to <10% malformations. Again the effects of PK11195 on EtOH teratogenicity is not yet known. The sampling time was chosen as the time of p53 protein induction (3.0h to 4.5h post-treatment). Whereas co-treatment with PK11195 suppresses embryonic p53 protein induction Ro5-4864 does not block this reaction. All measurements were on RNA from the embryonic headfold (8 d.p.c.) or prosencephalon (9 d.p.c.). Keywords = peripheral benzodiazepine receptor Keywords = Bzrp ligands Keywords = PK11195 Keywords = Ro5-4864 Keywords = embryo Keywords = p53 protein induction Keywords: ordered
2004-03-11 | GSE1072 | GEO
Project description:In this time course pregnant CD-1 (outbred) dams were exposed to MeHg as monomethylmercuric chloride intraperitoneally on 9 d.p.c. The test dose of 5.0 mg/kg MeHg was selected as a dose with an estimated 20% increased risk for encephalopathy in term fetuses, with no evidence of maternal toxicosis. Sampling intervals ranged from 1.5h to 24.0h post-exposure. All measurements were on RNA from the embryonic forebrain (prosencephalon) using contemporous control embryos as a reference. Keywords = time series Keywords = mercury Keywords = embryo Keywords = Fetal Minamata Disease Keywords: time-course
2004-03-11 | GSE1076 | GEO
Project description:With the advent of high information content technologies, especially microarrays, it is pertinent to determine the impact of molecular data on the NOAELs. Consequently, we conducted an integrative study to identify a no transcriptomic effect dose using microarray analyses coupled with qPCR and determined how this correlated with the NOAEL. We assessed the testicular effects of the antiandrogen, flutamide (FM), in a rat 28-day toxicity study using doses of 0.2-30 mg/kg/day. Concerning molecular data, we observed differential gene expression starting from 1 mg/kg/day and a deregulation of more than 1500 genes at 30 mg/kg/day. Dose-related changes were identified for the major pathways associated with the testicular lesion (eg fatty acid metabolism), that were confirmed by qPCR. These data, along with standard measurements supported the no effect dose of 0.2 mg/kg/day. Flutamide was administered in suspension to rats (7 weeks old at start of treatment, 10 per group) by oral gavage at a daily dose of 0 (control), 0.2, 1, 6 and 30 mg/kg body weight, for 28 consecutive days. Dose-related changes in gene expression were determined in the testes using whole genome oligonucleotide microarrays.
2011-03-29 | E-GEOD-28202 | biostudies-arrayexpress
Project description:Bisphenol A (BPA) is used in the plastic industry as the monomer of polycarbonates and epoxy resins. Heat and changes in pH conditions lead to its leakage from the plastics in which it is incorporated. This largely contributes to the widespread exposure of the general population to this environmental contaminant. The exposure levels in humans are likely below the Tolerable Daily Intake (TDI: 50 µg/kg/day) and well below the No Observable Adverse Effect Level (NOAEL: 5000 µg/kg/day) defined from reprotoxicity studies. However, several studies suggest that BPA could induce deleterious effects specifically at low, environmentally relevant, doses. BPA has been described as an endocrine disruptor with estrogenic activity. Recently, it has been shown that BPA exposure has an impact on metabolic functions including stimulation of adipogenesis and of insulin production by the pancreas. Here, we investigated the effects of oral exposure to low (TDI) and high (NOAEL) doses of BPA on mouse liver transcriptome. Liver gene expression was measured from CD-1 mice (6 mice/group) exposed for 28 days to bisphenol A at doses 0 (controls), 50 (TDI or low dose) or 5000 µg/kg/day (NOAEL or high dose) via food contamination.
2011-09-20 | E-GEOD-26728 | biostudies-arrayexpress
Project description:Systemic sclerosis is associated with skin fibrosis thought mediated by TGFb. This open label clinical trial examines the effect of TGFb inhibition on skin gene expression. Patients 1-9 received two doses 1 mg/kg dose of fresolimumab at baseline and 3 weeks; patients 10-19 received a single 5 mg/kg dose
2015-06-05 | GSE55036 | GEO
Project description:In this time course pregnant CD-1 (outbred) dams were exposed to the 2-chloro analogue of 2'-deoxyadenosine (a metabolic toxin) on 8 d.p.c. The test dose of 2.5 mg/kg 2CdA was modeled for a 5% increased risk of microphthalmia in term fetuses. Sampling intervals were anchored to the conditional biomarker (p53 protein induction) expressed in 2CdA-treated embryos between 3.0- and 4.5h post-exposure. Since p53 protein induction has been defined as a critical event in 2CdA-induced micropthalmia, these sampling intervals represent times before (3.0h), during (4.5h), and after (6.0h) this critical event. All measurements were on RNA from the embryonic headfold. Keywords = time series Keywords = 2-chloro-2'-deoxyadenosine Keywords = embryo Keywords = p53 protein induction Keywords = microphthalmia Keywords: time-course
2004-03-11 | GSE1069 | GEO