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Developmental Toxicity

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https://www.readbyqxmd.com/read/28436609/a-semi-automated-approach-to-create-purposeful-mechanistic-datasets-from-heterogeneous-data-data-mining-towards-the-in-silico-predictions-for-oestrogen-receptor-modulation-and-teratogenicity
#1
M Bashir Surfraz, Adrian Fowkes, Jeffrey P Plante
The need to find an alternative to costly animal studies for developmental and reproductive toxicity testing has shifted the focus considerably to the assessment of in vitro developmental toxicology models and the exploitation of pharmacological data for relevant molecular initiating events. We hereby demonstrate how automation can be applied successfully to handle heterogeneous oestrogen receptor data from ChEMBL. Applying expert-derived thresholds to specific bioactivities allowed an activity call to be attributed to each data entry...
April 24, 2017: Molecular Informatics
https://www.readbyqxmd.com/read/28433937/perturbation-effect-of-reduced-graphene-oxide-quantum-dots-rgoqds-on-aryl-hydrocarbon-receptor-ahr-pathway-in-zebrafish
#2
Jing-Hui Zhang, Tai Sun, Aping Niu, Yu-Mei Tang, Shun Deng, Wei Luo, Qun Xu, Dapeng Wei, De-Sheng Pei
Graphene quantum dots (GQDs) has been widely used in enormous fields, however, the inherent molecular mechanism of GQDs for potential risks in biological system is still elusive to date. In this study, the outstanding reduced graphene quantum dots (rGOQDs) with the QY as high as 24.62% were successfully synthesized by the improved Hummers method and DMF hydrothermal treatment approach. The rGOQDs were N-doped photoluminescent nanomaterials with functional groups on the surface. The fluorescent bio-imaging was performed by exposing zebrafish in different concentrations of the as-prepared rGOQDs, and the distribution of rGOQDs was successfully observed...
April 15, 2017: Biomaterials
https://www.readbyqxmd.com/read/28432637/polluted-pathways-mechanisms-of-metabolic-disruption-by-endocrine-disrupting-chemicals
#3
REVIEW
Mizuho S Mimoto, Angel Nadal, Robert M Sargis
PURPOSE OF REVIEW: Environmental toxicants are increasingly implicated in the global decline in metabolic health. Focusing on diabetes, herein, the molecular and cellular mechanisms by which metabolism disrupting chemicals (MDCs) impair energy homeostasis are discussed. RECENT FINDINGS: Emerging data implicate MDC perturbations in a variety of pathways as contributors to metabolic disease pathogenesis, with effects in diverse tissues regulating fuel utilization...
April 21, 2017: Current Environmental Health Reports
https://www.readbyqxmd.com/read/28431184/congener-specific-disposition-of-chiral-polychlorinated-biphenyls-in-lactating-mice-and-their-offspring-implications-for-pcb-developmental-neurotoxicity
#4
Izabela Kania-Korwel, Tracy Lukasiewicz, Christopher D Barnhart, Marianna Stamou, Haeun Chung, Kevin M Kelly, Stelvio Bandiera, Pamela J Lein, Hans-Joachim Lehmler
Chiral polychlorinated biphenyl (PCB) congeners have been implicated by laboratory and epidemiological studies in PCB developmental neurotoxicity. These congeners are metabolized by cytochrome P450 (P450) enzymes to potentially neurotoxic hydroxylated metabolites (OH-PCBs). The present study explores the enantioselective disposition and toxicity of two environmentally relevant, neurotoxic PCB congeners and their OH-PCB metabolites in lactating mice and their offspring following dietary exposure of the dam. Female C57BL/6N mice (8 weeks old) were fed daily, beginning two weeks prior to conception and continuing throughout gestation and lactation, with 3...
April 14, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28430390/chronic-toxicity-of-binary-metal-mixtures-of-cadmium-and-zinc-to-daphnia-magna
#5
Edgar Pérez, Tham C Hoang
The present study characterized the chronic effect of binary-metal mixtures of cadmium (Cd) and zinc (Zn) on Daphnia magna. The titration design was chosen to characterize the 21-d chronic effects of the binary-metal mixtures on survival, growth, reproduction, and metal accumulation in D. magna. Using this design, increasing concentrations of Zn (10, 20, 40, 80, 120, 160 and 200µg/L) were titrated against a constant concentration of 1.5µg/L Cd. The results demonstrated that Cd was highly toxic to D. magna...
April 21, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28430131/evaluation-of-tanshinone-iia-developmental-toxicity-in-zebrafish-embryos
#6
Tao Wang, Chengxi Wang, Qiong Wu, Kangdi Zheng, Jiaojiao Chen, Yutao Lan, Yao Qin, Wenjie Mei, Baoguo Wang
Tanshinone IIA (Tan-IIA) is derived from the dried roots of Salvia miltiorrhiza Bunge, a traditional Chinese medicine. Although Salvia miltiorrhiza has been applied for many years, the toxicity of the mono-constituent of Salvia miltiorrhiza, tanshinone IIA, is still understudied. This study evaluated the cardiotoxicity and developmental malformations of Tan-IIA by using zebrafish normal embryos and dechorionated embryos. After treatment with Tan-IIA in different concentrations for four-day periods, obvious pericardial edema, spinal curvature, and even missing tails were observed in zebrafish embryos...
April 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28428071/development-of-novel-in-silico-model-for-developmental-toxicity-assessment-by-using-na%C3%A3-ve-bayes-classifier-method
#7
Hui Zhang, Ji-Xia Ren, Yan-Li Kang, Peng Bo, Jun-Yu Liang, Lan Ding, Wei-Bao Kong, Ji Zhang
Toxicological testing associated with developmental toxicity endpoints are very expensive, time consuming and labor intensive. Thus, developing alternative approaches for developmental toxicity testing is an important and urgent task in the drug development filed. In this investigation, the naïve Bayes classifier was applied to develop a novel prediction model for developmental toxicity. The established prediction model was evaluated by the internal 5-fold cross validation and external test set. The overall prediction results for the internal 5-fold cross validation of the training set and external test set were 96...
April 18, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28422076/zeglobaltox-an-innovative-approach-to-address-organ-drug-toxicity-using-zebrafish
#8
Carles Cornet, Simone Calzolari, Rafael Miñana-Prieto, Sylvia Dyballa, Els van Doornmalen, Helma Rutjes, Thierry Savy, Davide D'Amico, Javier Terriente
Toxicity is one of the major attrition causes during the drug development process. In that line, cardio-, neuro-, and hepatotoxicities are among the main reasons behind the retirement of drugs in clinical phases and post market withdrawal. Zebrafish exploitation in high-throughput drug screening is becoming an important tool to assess the toxicity and efficacy of novel drugs. This animal model has, from early developmental stages, fully functional organs from a physiological point of view. Thus, drug-induced organ-toxicity can be detected in larval stages, allowing a high predictive power on possible human drug-induced liabilities...
April 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28417904/zebrafish-as-an-alternative-vertebrate-model-for-investigating-developmental-toxicity-the-triadimefon-example
#9
Maria Zoupa, Kyriaki Machera
Triadimefon is a widely used triazole fungicide known to cause severe developmental defects in several model organisms and in humans. The present study evaluated in detail the developmental effects seen in zebrafish embryos exposed to triadimefon, confirmed and expanded upon previous phenotypic findings and compared them to those observed in other traditional animal models. In order to do this, we exposed embryos to 2 and 4 µg/mL triadimefon and evaluated growth until 120 h post-fertilization (hpf) through gross morphology examination...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28417441/relationships-between-essential-manganese-biology-and-manganese-toxicity-in-neurological-disease
#10
REVIEW
Anna C Pfalzer, Aaron B Bowman
PURPOSE OF REVIEW: Manganese (Mn) is critical for neurodevelopment but also has been implicated in the pathophysiology of several neurological diseases. We discuss how Mn requirements intersect with Mn biology and toxicity, and how these requirements may be altered in neurological disease. Furthermore, we discuss the emerging evidence that the level of Mn associated with optimal overall efficiency for Mn biology does not necessarily coincide with optimal cognitive outcomes. RECENT FINDINGS: Studies have linked Mn exposures with urea cycle metabolism and autophagy, with evidence that exposures typically neurotoxic may be able to correct deficiencies in these processes at least short term...
April 17, 2017: Current Environmental Health Reports
https://www.readbyqxmd.com/read/28417285/alcohol-and-thiamine-deficiency-trigger-differential-mitochondrial-transition-pore-opening-mediating-cellular-death
#11
REVIEW
Abdoulaye Bâ
Accumulating evidence has shown that binge-type alcohol intake in mothers interferes with thiamine deficiency (TD) to promote the fetal alcohol syndrome (FAS). Developmental alcohol or TD exposures act either synergistically or separately to reproduce FAS features e.g. intrauterine growth retardation and related microcephaly characterized by extensive cellular death induced by one another neurotoxicant. However molecular and cellular mechanisms underlying apoptosis in both alcohol and TD toxicities are unknown...
June 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28414088/embryonic-vascular-disruption-adverse-outcomes-linking-high-throughput-signaling-signatures-with-functional-consequences
#12
Robert G Ellis-Hutchings, Raja S Settivari, Alene T McCoy, Nicole Kleinstreuer, Jill Franzosa, Thomas B Knudsen, Edward W Carney
Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High-throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay...
April 13, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28409340/drosophila-malpighian-tubules-a-model-for-understanding-kidney-development-function-and-disease
#13
Naveen Kumar Gautam, Puja Verma, Madhu G Tapadia
The Malpighian tubules of insects are structurally simple but functionally important organs, and their integrity is important for the normal excretory process. They are functional analogs of human kidneys which are important physiological organs as they maintain water and electrolyte balance in the blood and simultaneously help the body to get rid of waste and toxic products after various metabolic activities. In addition, it receives early indications of insults to the body such as immune challenge and other toxic components and is essential for sustaining life...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28407592/different-effects-of-bisphenol-a-and-its-halogenated-derivatives-on-the-reproduction-and-development-of-oryzias-melastigma-under-environmentally-relevant-doses
#14
Qiansheng Huang, Yajie Chen, Lifeng Lin, Yiyao Liu, Yulang Chi, Yi Lin, Guozhu Ye, Huiming Zhu, Sijun Dong
Bisphenol A (BPA) and its halogenated compounds (H-BPAs) are widely detected in the environmental media and organisms. However, their toxicological effects, especially chronic exposure at low doses, have not been fully compared. In this study, the effects of BPA and H-BPAs on the reproduction and development of Oryzias melastigma were systematically assessed and compared at various developmental stages. BPA and its derivatives tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) elicited the acceleration of embryonic heartbeat...
April 10, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28407156/enhancing-care-models-to-capture-psychological-trauma
#15
Mary Suzanne Balch, Jo Loomis
Toxic levels of stress in childhood are an ongoing threat to public health. Traumatized children have special needs for health care to address their developmental, mental health, and medical problems, and mitigate risk for long-term health problems. Developmental trauma leads to increased use of medical, social, correctional, and mental health services. Longitudinal and retrospective studies link childhood trauma and adversity to academic difficulties, poor health, and low economic productivity in adulthood...
April 1, 2017: Journal of Psychosocial Nursing and Mental Health Services
https://www.readbyqxmd.com/read/28405934/a-brief-review-of-neurotoxicity-induced-by-melamine
#16
REVIEW
Lei An, Wei Sun
In September 2008, in China, tens of thousands of children were hospitalized, several even died, as a result of infant-formula milk adulterated with a synthetic chemical compound, melamine, and in the next few months, this crisis became the focus of attention worldwide. Although there are a number of articles about nephrotoxicity of melamine, the evidence of melamine toxicity on other organs is still scanty. Specially, several recent studies indicated that melamine can perturb the central nervous system (CNS) function and induce cognitive deficits, breaking the previous view that melamine toxicity is limited to the urinary system...
April 13, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28405838/acaricidal-and-sublethal-effects-of-a-chenopodium-based-biopesticide-on-the-two-spotted-spider-mite-acari-tetranychidae
#17
Asma Musa, Irena Međo, Ivana Marić, Dejan Marčić
Acaricidal and sublethal effects of the biopesticide Requiem(®)EC (containing an essential oil extract of Chenopodium ambrosioides near ambrosioides) on the two-spotted spider mite, Tetranychus urticae Koch, were evaluated in laboratory bioassays. The biopesticide was applied to bean leaves or leaf discs using a Potter spray tower. Acaricidal activity against eggs and immatures was evaluated in successive acute toxicity bioassays. Concentration-mortality data were subjected to probit analysis and the following LC50 values (ml/l) were calculated: 2...
April 12, 2017: Experimental & Applied Acarology
https://www.readbyqxmd.com/read/28398632/prenatal-and-postnatal-assessment-in-rabbits-with-evacetrapib-a-cholesteryl-ester-transfer-protein-inhibitor
#18
William J Breslin, Kim G Hilbish, Ellen A Cannady, Tammy L Edwards
BACKGROUND: Evacetrapib, a potent and selective inhibitor of cholesteryl ester transfer protein (CETP), was under development for the treatment of cardiovascular (CV) disease. The purpose of this pre-postnatal study in rabbits was to evaluate the effects of evacetrapib on pregnancy, parturition, and lactation of the maternal animals and on the growth, viability, development, and reproductive performance of the first filial (F1) offspring. The rabbit is considered a relevant species for toxicity testing with evacetrapib as it demonstrates significant CETP expression, whereas mice and rats do not express significant levels of CETP...
April 17, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28395206/effects-of-gamma-radiation-on-the-early-developmental-stages-of-zebrafish-danio-rerio
#19
M K Praveen Kumar, S K Shyama, Shamim Kashif, S K Dubey, D'costa Avelyno, B H Sonaye, B Kadam Samit, R C Chaubey
The zebrafish is gaining importance as a popular vertebrate model organism and is widely employed in ecotoxicological studies, especially for the biomonitoring of pollution in water bodies. There is limited data on the genetic mechanisms governing the adverse health effects in regards to an early developmental exposure to gamma radiation. In the present study zebrafish (Danio rerio) embryos were exposed to 1, 2.5, 5, 7.5 and 10Gy of gamma radiation at 3h post fertilization (hpf). Different developmental toxicity endpoints were investigated...
April 7, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28393070/assessment-of-toxicological-perturbations-and-variants-of-pancreatic-islet-development-in-the-zebrafish-model
#20
Karilyn E Sant, Haydee M Jacobs, Jiali Xu, Katrina A Borofski, Larry G Moss, Jennifer B Moss, Alicia R Timme-Laragy
The pancreatic islets, largely comprised of insulin-producing beta cells, play a critical role in endocrine signaling and glucose homeostasis. Because they have low levels of antioxidant defenses and a high perfusion rate, the endocrine islets may be a highly susceptible target tissue of chemical exposures. However, this endpoint, as well as the integrity of the surrounding exocrine pancreas, is often overlooked in studies of developmental toxicology. Disruption of development by toxicants can alter cell fate and migration, resulting in structural alterations that are difficult to detect in mammalian embryo systems, but that are easily observed in the zebrafish embryo model (Danio rerio)...
September 2016: Toxics
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