Project description:Six samples of N27 cells were treated with 25 uM fipronil, and 6 samples were not treated (control). The treatment proceeded for 24 hours.
Project description:N27 cells are dopaminergic neurons derived from rat midbrain and are extensively employed as a model for neurodegeneration. N27 cells were challenged with 2 neurotoxins associated with Manganism (Manganese Chloride;Mn) and Parkinson's Disease (1-methyl-4-phenylpyridinium ion;MPP+). Mn and MPP+ result in movement dysfunction and are mitochondrial toxins particularly affecting complexes I.This study aimed to understand and differentiate the molecular mechanisms underlying Mn and MPP+ mediated dopaminergic insult by evaluating the differential gene expression pattern in the two models
Project description:Global gene expression indicated that N27 neurons exposed to each nanoAg material (1.0 ppm, 18 hr) responded primarily to PVP coated nanoAg of both sizes with affected pathways largely associated with mitochondrial dysfunction (PVP 75 nm nanoAg) and Nrf-2 mediated oxidative stress (PVP 10 nm nanoAg) pathways. N27 rat dopaminergic neurons were exposed to non-cytoxic (0.5-5.0 ppm) concentrations of nanoAg of different sizes (10 nm, 75 nm) and “cappings” (PVP, citrate).
Project description:The phenylpyrazole fipronil is a widely used insecticide designed to inhibit γ -amino-butyric acid (GABA) receptors, the major inhibitory neurotransmitter in the central nervous system. Fipronil has been detected in some water systems in the ng/L range, and is reported to be neurotoxic. To address the risks associated with fipronil exposure, we measured morphological, physiological, and molecular responses in zebrafish (Danio rerio) embryos following a 48 hour exposure (20 ng/L – 2 mg/L). Survival was not different than controls following treatments below 200 µg fipronil/L but was ~20% higher with concentrations above 200 µg fipronil/L. Once the embryos hatched, they underwent a 7 day depuration phase. At 9 days post-fertilization (9 dpf), body length and notochord length were not different than controls for any dose. To assess sub-lethal effects, transcriptome profiling was conducted in 9 dpf larvae following 48 hour exposure + 7 dpf depuration to environmentally relevant concentrations of fipronil (200 ng fipronil/L), as well as two higher concentrations of the pesticide (200 µg fipronil/L and 2 mg fipronil/L). Transcriptome profiling revealed that all three concentrations affected pathways related to chromosome condensation and the metabolism of estrogens and androgens as well as genes related to methylation. In addition, 200 ng fipronil/L down-regulated genes related to the circadian clock, histone and DNA methylation, and histone acetylation, while the highest dose increased networks related to immune function (e.g. lectin-induced complement pathway and the alternative complement pathway). The two highest concentrations of fipronil increased the expression of transcriptional networks associated with mitochondrial respiratory chain dysfunction and mitochondrial protein transport. As such, we exposed 24 hpf embryos to fipronil for 24 hours and measured oxygen consumption rate to assess mitochondrial function. There were no differences in basal and maximal respiration in the embryos nor ATP production, and fipronil did not affect mitochondrial bioenergetics. This study suggests that fipronil at environmentally relevant concentrations does not adversely affect the survival or morphology of fish embryos, however sub-lethal endpoints should be examined to more fully characterize the long term effects of fipronil exposure in larval fish.
Project description:The biological effects of the pesticide and complex I inhibitor tebufenpyrad (TEBU) on liver cells were investigated by proteomic approaches. Cellular contents and culture media were analyzed in dose-response experiments on primary rat hepatocytes (PRHs).
Project description:Fipronil is a widely-used broad-spectrum phenylpyrazole insecticide. It has been shown that fipronil increases the hepatic metabolism of thyroid hormone in the rat, which may induce compensatory mechanisms at the level of the thyroid gland itself. Here, we studied the effect of fipronil on the transcriptome of the thyroid gland in the rat. Adult (2- to 3-month-old) female Wistar rats were treated per os with fipronil (3 mg/kg) or the vehicle alone for 14 days. The transcriptome of their thyroid gland was analyzed using Agilent 4x44K microarrays.
Project description:Fipronil (CAS #: 120068-37-3), a widely used insecticide, has been described as a thyroid disruptor in rat inducing a marked increase in thyroxine (T4) clearance resulting in a decrease in T4 plasma concentration. These effects seem to require the bioactivation of fipronil via its biotransformation into fipronil sulfone by cytochromes P450 (CYP). Here, we hypothesized that fipronil-induced thyroid disruption may, at least in part, result from the induction of hepatic enzymes involved in the metabolism of thyroid hormones. Thus, we used microarrays to perform a genome-wide analysis of the effects of fipronil on gene expression in rat liver.
Project description:Fipronil is a widely-used broad-spectrum phenylpyrazole insecticide. It has been shown that fipronil increases the hepatic metabolism of thyroid hormone in the rat, which may induce compensatory mechanisms at the level of the thyroid gland itself. Here, we studied the effect of fipronil on the transcriptome of the thyroid gland in the rat. Adult (2- to 3-month-old) female Wistar rats were treated per os with fipronil (3 mg/kg) or the vehicle alone for 14 days. The transcriptome of their thyroid gland was analyzed using Agilent 4x44K microarrays. Thyroid gland gene expression was measured from female Wistar rats treated with vehicle (n = 10) or fipronil (n = 10) using a dye switch design.
Project description:The environmental factors such as pesticides could affect the developmental processes and cause the phenotypic changes. Moreover, the changes could be transferred to a subsequent generation via gametes. In this project we studied whether the pesticide chlordecone could cause the developmental effects and cause the transgenerational inheritance in outbred mouse strain (Swiss). Mice were treated during development (E6.5-E15.5) at dose 100 µg/kg/day and the progeny of exposed mice (F1) were crossed for three generations. The prostate of the first (F1) and third generation males (F3) were used for RNA-seq-analysis. We used three biological replicates for each condition.