Methodoligies for identifying lead toxicity
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE37567 | GEO | 2012/06/01
SECONDARY ACCESSION(S): PRJNA161869
REPOSITORIES: GEO
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Project description:75 Diosophilia Roo lines, recominant inbred lines, were raised to adulthood either on conventional diet or diet supplemented with lead acetate. Whole flies were used for RNA extraction. RNA was run on Dros Genome 2 arrays. Each line also genotyped for 88 markers; Control food consisted of standard cornmeal, agar, sugar, yeast, and 250 microM NaAc (Ashburner 1989). Lead-contaminated food consisted of standard food plus 250 microM PbAc (lead exposure at this concentration has been shown to affect locomotion in adults (Hirsch et al. 2003)). Experiment Overall Design: 75 RI lines each line treated and untreated with lead acetate
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Project description:Lead is a ubiquitous environmental and industrial pollutant. Its nonbiodegradable toxicity induces a plethora of human diseases. The current study was undertaken to purify a novel 252-kDa bioactive glycoprotein containing 1.15% carbohydrate from the edible fungus Auricularia polytricha with the ability of adsorbing lead and producing detoxification. The A. polytricha detoxifying glycoprotein (APL), which displayed unique molecular properties, was purified by ion exchange chromatography and gel filtration chromatography. For investigating the protective effects of A. polytricha, Sprague Dawley (SD) rats were divided into six groups which received daily intraperitoneal injection of lead acetate for 30 days, followed by gavage with APL (40, 80, 160 mg/kg B body weight) and EDTA (300 mg/kg body weight) for 30 days after successful establishment of an animal model of lead detoxification. The serum concentrations of lead and the liver biomarkers AST and ALT were significantly (p<0.05) improved by APL treatments, as well as treatment with the positive control EDTA. Likewise, results on lead residue showed that the clearance ratios of liver and kidney were respectively 44.5% and 18.1% at the high APL dosage, which was even better than the corresponding data for EDTA. Proteomics disclosed that 351 proteins differentially expressed due to lead exposure and the expression levels of 41 proteins enriched in the pathways mainly involved in cell detoxification and immune regulation were normalized after treatment with APL-H. Our results signify that APL may ameliorate lead-induced hepatorenal injury by positive regulation of immune processing, and suggest that APL be applied as a therapeutic intervention of lead poisoning in clinic treatment. This report represents the first demonstration of the protective action of a novel mushroom protein on lead-elicited hepatorenal toxicity.
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Project description:Despite major successes in reducing the risks of lead (Pb) exposure over the past few decades, two issues of considerable importance remain unresolved: (1) how differences in water chemistry influence acute and chronic Pb toxicity, and (2) the elucidation of specific toxic mechanisms and modes of action (MOA). To more clearly define the water chemistry parameters mediating Pb toxicity we evaluated the effects of hardness (as CaSO4) and DOC (as humic acid (HA)) during chronic (150d) exposures to the fathead minnow (Pimephales promelas). Traditional toxicological endpoints were examined alongside gene expression analyses to help clarify the underlying mechanisms and MOA of Pb toxicity and to identify robust molecular markers of exposure and effect. Keywords: time course, chronic lead (Pb) exposure To analyze the gene expression responses to low-level Pb exposures fish were exposed +/- Pb in low ionic strength base water and fish collected at 2d, 4d, 10d, and 30d for microarray analysis. Equal amounts of RNA from all no lead controls were pooled (18 fish total for 2d & 4d exposures; 12 fish total for 10d & 30d exposures) as reference samples for hybridization with each of 3 separate biological replicate pools (6 fish total for 2d & 4d exposures; 4 fish total for 10d & 30d exposures) of RNA from age-matched, lead-exposed fish. Each pair of hybridizations was repeated with dye-swaps. Additional repeats were performed for various arrays to ensure quality of data obtained from initial hybridization.
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Project description:Despite major successes in reducing the risks of lead (Pb) exposure over the past few decades, two issues of considerable importance remain unresolved: (1) how differences in water chemistry influence acute and chronic Pb toxicity, and (2) the elucidation of specific toxic mechanisms and modes of action (MOA). To more clearly define the water chemistry parameters mediating Pb toxicity we evaluated the effects of hardness (as CaSO4) and DOC (as humic acid (HA)) during chronic (150d) exposures to the fathead minnow (Pimephales promelas). Traditional toxicological endpoints were examined alongside gene expression analyses to help clarify the underlying mechanisms and MOA of Pb toxicity and to identify robust molecular markers of exposure and effect. Keywords: time course, chronic lead (Pb) exposure
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