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Richard E Peterson - One of the best experts on this subject based on the ideXlab platform.
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2 3 7 8 tetrachlorodibenzo p dioxin activation of the aryl hydrocarbon receptor aryl hydrocarbon receptor nuclear translocator pathway causes developmental toxicity through a cyp1a independent mechanism in zebrafish
Molecular Pharmacology, 2004Co-Authors: Sara A Carney, Richard E Peterson, Warren HeidemanAbstract:The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that dimerizes with ARNT to mediate responses to compounds such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD and other AHR agonists cause toxic responses in early life stages of fish, including the zebrafish, Danio rerio. The most well characterized target gene for the AHR/aryl hydrocarbon receptor nuclear translocator (ARNT) dimer is a cytochrome P450, CYP1A. Induction of CYP1A by TCDD has been correlated with certain toxic responses in developing zebrafish and has been postulated to mediate these responses. To determine whether CYP1A is the important downstream effector enzyme for the AHR/ARNT pathway, we used morpholino oligonucleotides (MOs) to block induction of CYP1A in response to TCDD in zebrafish embryos. Although the zfcyp1a-MO effectively prevented CYP1A up-regulation, it did not prevent the signs of developmental toxicity, including pericardial edema, slowed blood flow, Craniofacial Malformation, and defects in erythropoiesis. We conclude that the important target for the AHR/ARNT pathway in developing zebrafish exposed to TCDD is not zfcyp1a. This suggests an alternative model in which TCDD-activated AHR/ARNT disrupts the normal process of growth and development by altering programs of gene expression or function.
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2 3 7 8 tetrachlorodibenzo p dioxin alters cardiovascular and Craniofacial development and function in sac fry of rainbow trout oncorhynchus mykiss
Toxicological Sciences, 1999Co-Authors: Michael W Hornung, Jan M Spitsbergen, Richard E PetersonAbstract:Hallmark signs of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity in rainbow trout sac fry, are yolk sac edema, hemorrhage, Craniofacial Malformation, and growth retardation culminating in mortality. Our objective was to determine the role of cardiovascular dysfunction in the development of this toxicity. An embryotoxic TCDD dose (385 pg/g egg) caused a progressive reduction in blood flow in rainbow trout sac fry manifested first and most dramatically in the 1st and 2nd branchial arches and vessels perfusing the lower jaw. Blood flow was reduced later in the infraorbital artery and occipital vein of the head as well as segmental vessels and caudal vein of the trunk. Reduced perfusion occurred last in gill branchial arteries involved with oxygen uptake and the subintestinal vein and vitelline vein involved with nutrient uptake. Although heart rate throughout sac fry development was not affected, heart size at 50 days post-fertilization (dpf) was reduced far more than body weight or length, suggesting that the progressive circulatory failure caused by TCDD is associated with reduced cardiac output. Craniofacial development was arrested near hatch, giving rise to Craniofacial Malformations in which the jaws and anterior nasal structures were underdeveloped. Unlike the medaka embryo, in which TCDD causes apoptosis in the medial yolk vein, endothelial cell death was not observed in rainbow trout sac fry. These findings suggest a primary role for arrested heart development and reduced perfusion of tissues with blood in the early-life stage toxicity of TCDD in trout.
Warren Heideman - One of the best experts on this subject based on the ideXlab platform.
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2 3 7 8 tetrachlorodibenzo p dioxin activation of the aryl hydrocarbon receptor aryl hydrocarbon receptor nuclear translocator pathway causes developmental toxicity through a cyp1a independent mechanism in zebrafish
Molecular Pharmacology, 2004Co-Authors: Sara A Carney, Richard E Peterson, Warren HeidemanAbstract:The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that dimerizes with ARNT to mediate responses to compounds such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD and other AHR agonists cause toxic responses in early life stages of fish, including the zebrafish, Danio rerio. The most well characterized target gene for the AHR/aryl hydrocarbon receptor nuclear translocator (ARNT) dimer is a cytochrome P450, CYP1A. Induction of CYP1A by TCDD has been correlated with certain toxic responses in developing zebrafish and has been postulated to mediate these responses. To determine whether CYP1A is the important downstream effector enzyme for the AHR/ARNT pathway, we used morpholino oligonucleotides (MOs) to block induction of CYP1A in response to TCDD in zebrafish embryos. Although the zfcyp1a-MO effectively prevented CYP1A up-regulation, it did not prevent the signs of developmental toxicity, including pericardial edema, slowed blood flow, Craniofacial Malformation, and defects in erythropoiesis. We conclude that the important target for the AHR/ARNT pathway in developing zebrafish exposed to TCDD is not zfcyp1a. This suggests an alternative model in which TCDD-activated AHR/ARNT disrupts the normal process of growth and development by altering programs of gene expression or function.
Nilson Antonio Assuncao - One of the best experts on this subject based on the ideXlab platform.
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profiles of amino acids and biogenic amines in the plasma of cri du chat patients
Journal of Pharmaceutical and Biomedical Analysis, 2017Co-Authors: Danielle Zildeana Sousa Furtado, Fernando Brunale Vilela De Moura Leite, Cleber Nunes Barreto, Bernadete Faria, Leticia Dias Lima Jedlicka, Elisângela De Jesus Silva, Heron Dominguez Torres Da Silva, Etelvino J H Bechara, Nilson Antonio AssuncaoAbstract:Abstract Cri-du-chat syndrome (CDCS) is a rare innate disease attributed to chromosome 5p deletion characterized by a cat-like cry, Craniofacial Malformation, and altered behavior of affected children. Metabolomic analysis and a chemometric approach allow description of the metabolic profile of CDCS as compared to normal subjects. In the present work, UHPLC/MS was employed to analyze blood samples withdrawn from CDCS carriers (n = 18) and normal parental subjects (n = 18), all aged 0–34 years, aiming to set up a representative CDCS profile constructed from 33 targeted amino acids and biogenic amines. Methionine sulfoxide (MetO) was of particular concern with respect to CDCS redox balance. Increased serotonin (3-fold), methionine sulfoxide (2-fold), and Asp levels, and a little lower Orn, citrulline, Leu, Val, Ile, Asn, Gln, Trp, Thr, His, Phe, Met, and creatinine levels were found in the plasma of CDCS patients. Nitrotyrosine and Trp did not differ in normal and CDCS individuals.The accumulated metabolites may reflect, respectively, disturbances in the redox balance, deficient purine biosynthesis, and altered behavior, whereas the amino acid abatement in the latter group may affect the homeostasis of the urea cycle, citric acid cycle, branched chain amino acid synthesis, Tyr and Trp metabolism and amino acid biosynthesis. The identification of enzymatic deficiencies leading to the amino acid burden in CDCS is further required for elucidating its molecular bases and eventually propose specific or mixed amino acid supplementation to newborn patients aiming to balance their metabolism.
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metabolomic based amino acid and biogenic amine plasmatic profile of brazilian cri du chat patients
Free Radical Biology and Medicine, 2016Co-Authors: Etelvino J H Bechara, Fernando Brunale Vilela De Moura Leite, Cleber Nunes Barreto, Heron Dominguez Torres Da Silva, Danielle Furtado, Elisangela Silva, Nilson Antonio AssuncaoAbstract:Cri-du-chat syndrome (CDCS) is a rare innate disease attributed to chromosome 5p deletion characterized by a cat-like cry, Craniofacial Malformation, and altered behavior of affected children. Here, UHPLC/MS and chemometrics were employed to analyze blood samples withdrawn from CDCS carriers (n=18) and normal parental subjects (n=18), all aged 0-34 years, aiming to set up a representative CDCS profile constructed from 33 targeted amino acids and biogenic amines. Methionine sulfoxide (MetO), nitrotyrosine and His were of particular concern with respect to CDCS redox balance. Increased serotonin (3-fold), methionine sulfoxide (2-fold), and Asp (50%) levels, and a little lower Orn (26%), citrulline (23%), Leu (29%), Val (20%), Ile (16%), Asn (17%), Gln (10%), Trp (15%), Thr (13%), His (12%), Phe (11%), Met (6%), and creatinine (35%) levels were found in the plasma of CDCS patients. Nitrotyrosine did not differ in normal and CDCS individuals, whereas the ratio Trp/Σtotal metabolites was 37% higher in the latter group. The accumulated metabolites may reflect disturbances in the redox balance, deficient purine biosynthesis, and altered behavior, whereas the amino acid abatement in the latter group may affect the homeostasis of the urea cycle, citric acid cycle, branched chain amino acid synthesis, Tyr and Trp metabolism and amino acid biosynthesis. The identification of enzymatic deficiencies leading to the amino acid burden in CDCS is further required for elucidating its molecular bases and eventually propose specific or mixed amino acid supplementation to newborn patients aiming to balance their metabolism. Support: FAPESP, CNPq, CAPES.
Sonnich Meier - One of the best experts on this subject based on the ideXlab platform.
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oil droplet fouling and differential toxicokinetics of polycyclic aromatic hydrocarbons in embryos of atlantic haddock and cod
PLOS ONE, 2017Co-Authors: Lisbet Sorensen, Trond Nordtug, Elin Sorhus, John P Incardona, Tiffany L Linbo, Laura Giovanetti, Orjan Karlsen, Sonnich MeierAbstract:The impact of crude oil pollution on early life stages (ELS) of fish, including larvae and embryos, has received considerable attention in recent years. Of the organic components present in crude oil, polycyclic aromatic hydrocarbons (PAHs) are considered the main class of compounds responsible for toxic effects in marine organisms. Although evidence suggests that they are more toxic, alkylated PAHs remain much less studied than their unsubstituted congeners. Recently, it was established that embryos of Atlantic haddock (Melanogrammus aeglefinus) are particularly sensitive to dispersed crude oil, and it was hypothesized that this was caused by direct interaction with crude oil droplets, which adhered to the chorion of exposed embryos. Such a phenomenon would increase the potential for uptake of less water-soluble compounds, including alkylated PAHs. In the current study, we compared the uptake of parent and alkylated PAHs in Atlantic cod (Gadus morhua) and haddock embryos exposed to dispersed crude oil at a range of environmentally relevant concentrations (10–600 μg oil/liter seawater). Although the species are biologically very similar, the cod chorion does not become fouled with oil droplets, even when the two species are exposed to dispersions of crude oil droplets under similar conditions. A close correlation between the degree of fouling and toxicological response (heart defects, Craniofacial Malformation) was observed. Oil droplet fouling in haddock led to both quantitative and qualitative differences in PAH uptake. Finally, kinetic data on a large suite of PAHs showed differential elimination, suggesting differential metabolism of unsubstituted versus alkylated compounds.
Sara A Carney - One of the best experts on this subject based on the ideXlab platform.
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2 3 7 8 tetrachlorodibenzo p dioxin activation of the aryl hydrocarbon receptor aryl hydrocarbon receptor nuclear translocator pathway causes developmental toxicity through a cyp1a independent mechanism in zebrafish
Molecular Pharmacology, 2004Co-Authors: Sara A Carney, Richard E Peterson, Warren HeidemanAbstract:The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that dimerizes with ARNT to mediate responses to compounds such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD and other AHR agonists cause toxic responses in early life stages of fish, including the zebrafish, Danio rerio. The most well characterized target gene for the AHR/aryl hydrocarbon receptor nuclear translocator (ARNT) dimer is a cytochrome P450, CYP1A. Induction of CYP1A by TCDD has been correlated with certain toxic responses in developing zebrafish and has been postulated to mediate these responses. To determine whether CYP1A is the important downstream effector enzyme for the AHR/ARNT pathway, we used morpholino oligonucleotides (MOs) to block induction of CYP1A in response to TCDD in zebrafish embryos. Although the zfcyp1a-MO effectively prevented CYP1A up-regulation, it did not prevent the signs of developmental toxicity, including pericardial edema, slowed blood flow, Craniofacial Malformation, and defects in erythropoiesis. We conclude that the important target for the AHR/ARNT pathway in developing zebrafish exposed to TCDD is not zfcyp1a. This suggests an alternative model in which TCDD-activated AHR/ARNT disrupts the normal process of growth and development by altering programs of gene expression or function.