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Human neuronal cell based assay : a new in vitro model for toxicity evaluation of ciguatoxin
No full textCiguatoxins (CTXs) are emerging marine neurotoxins representing the main cause of ciguatera fish poisoning, an intoxication syndrome which configures a health emergency and constitutes an evolving issue constantly changing due to new vectors and derivatives of CTXs, as well as their presence in new non-endemic areas. The study applied the neuroblastoma cell model of human origin (SH-SY5Y) to evaluate species-specific mechanistic information on CTX toxicity. Metabolic functionality, cell morphology, cytosolic Ca2+ i responses, neuronal cell growth and proliferation were assessed after short- (4–24 h) and long-term exposure (10days) to P-CTX-3C. In SH-SY5Y, P-CTX-3C displayed a powerful cytotoxicity requiring the presence of both Veratridine and Ouabain. SH-SY5Y were very sensitive to Ouabain: 10 and 0.25 nM appeared the optimal concentrations, for short- and long-term toxicity studies, respectively, to be used in co-incubation with Veratridine (25 μM), simulating the physiological and pathological endogenous Ouabain levels in humans. P-CTX-3C cytotoxic effect, on human neurons co-incubated with OV (Ouabain + Veratridine) mix, was expressed starting from 100 pM after short- and 25 pM after long-term exposure. Notably, P-CTX-3C alone at 25 nM induced cytotoxicity after 24 h and prolonged exposure. This human brain-derived cell line appears a suitable cell-based-model to evaluate cytotoxicity of CTX present in marine food contaminated at low toxic levels and to characterize the toxicological profile of other/new congeners
Human Co-culture Model of Neurons and Astrocytes to Test Acute Cytotoxicity of Neurotoxic Compounds
No full textAlternative methods and their use in planning and conducting toxicology experiments have become essential for modern toxicologists, thus reducing or replacing living animals. Although in vitro human co-culture models allow the establishment of biologically relevant cell-cell interactions that recapitulate the tissue microenvironment and better mimic its physiology, the number of publications is limited specifically addressing this scientific area and utilizing this test method which could provide an additional valuable model in toxicological studies. In the present study, an in vitro model based on central nervous system (CNS) cell co-cultures was implemented using a transwell system combining human neuronal cells (SH-SY5Y cell line) and glial cells, namely astrocytes (D384 cell line), to investigate neuroprotection of D384 on SH-SY5Y and vice versa. The model was applied to test acute (24-48 hours) cytotoxicity of 3 different neurotoxicants: (1) methyl mercury (1-2.5 μM), (2) Fe3O4 nanoparticles (1-100 μg/mL), and (3) methylglyoxal (0.5-1 mM). Data were compared to mono-cultures evaluating the mitochondrial function and cell morphology. The results clearly showed that all compounds tested affected the mitochondrial activity and cell morphology in both mono-culture and co-culture conditions. However, astrocytes, when cultured together with neurons, diminish the neurotoxicant-induced cytotoxic effects that occurred in neurons cultured alone, and astrocytes become more resistant in the presence of neurons. This human CNS co-culture system seems a suitable cell model to feed high-throughput acute screening platforms and to evaluate both human neuronal and astrocytic toxicity and neuroprotective effects of new and emerging materials (eg, nanomaterials) and new products with improved sensitivity due to the functional neuron-astrocyte metabolic interactions
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Effects of developmental exposure to Methylmercury on cholinergic receptors at the weaning and puberty in rat
No full textEffects of water-soluble functionalized multi-walled carbon nanotubes examined by different cytotoxicity methods in human astrocyte D384 and lung A549 cells.
No full textTwo cell culture systems, human A549 pneumocytes and D384
astrocytoma cells, were used to assess cytotoxicity of multi-walled CNTs (MWCNTs) with varying degrees of functionalization. Laboratory-made highly functionalized hf-MW-NH2 and less functionalized CNTs (MW-COOH and MW-NH2) were tested in comparison with pristine MWCNTs, carbon black (CB) and silica
(SiO2) by MTT assay and calcein/propidium iodide (PI) staining. Purity and physicochemical properties of the test nanomaterials were also determined.
In both MTT and calcein/PI assays, highly functionalized CNTs (hf-MW-NH2) caused moderate loss of
cell viability at doses ≥100g/ml being apparently less cytotoxic than SiO2.
In preparations treated with CB or the other nanotube types (pristine MWCNTs, MW-COOH and the less functionalized amino-substituted MW-NH2) the calcein/PI test indicated no loss of cell viability, whereas MTT assay apparently showed apparent cytotoxic response, occurring not dose-dependently at
exceedingly low CNT concentrations (1g/ml). The latter nanomaterials were difficult to disperse showing higher aggregate ranges and tendency to agglomerate in bundle-like form in cell cultures. In contrast, hf-MW-NH2 were water soluble and easily dispersible in medium; they presented lower aggregate size
range as well as considerably lower length to diameter ratios and low tendency to form aggregates compared to the other CNTs tested. The MTT data may reflect a false positive cytotoxicity signal possibly due to non-specific CNT interaction with cell culture components.
Thus, these properties obtained by chemical functionalization, such as water solubility, high dispersibility and low agglomeration tendency were relevant factors in modulating cytotoxicity.
This study indicates that properties obtained by chemical functionalization, such as water solubility, high dispersibility and low agglomeration tendency are relevant factors in modulating cytotoxicity of CNTs
Gene Expression Changes in Rat Liver and Testes after Lung Instillation of a Low Dose of Silver Nanoparticles
Get PDFThe expression profile of genes involved in oxidative stress, metal toxicity, apoptosis/cell cycle, and protein folding was investigated in liver and testis of Sprague-Dawley rats at different time intervals after i.t. instillation of AgNP (20 nm, 50 μg/rat). At 7 days, selective changes in the expression of genes encoding oxidative stress-related enzymes, namely Gpx1, SOD, FMO2 and GAPDH were observed in hepatic and testicular tissues. Other genes implicated in oxidative stress (Txnrd1, Gss, Gsr), metal toxicity (Mt1), apoptosis/cell cycle (casp3, p53), and protein-folding processes (Hsp70) were not modified. Gene expression was modulated by AgNPs in a tissue- and time-dependent manner. In particular, SOD was up-regulated in both tissues, but significant Gpx1, FMO2, and GAPDH overexpression was seen in testes only. No gene expression changes were seen in both tissues 28 days post-instillation. Unlike AgNPs, pulmonary treatment with AgNO3 (7 μg/rat), did not cause gene expression changes in both tissues at both time points studied, suggesting that dissimilar mechanisms are implicated in toxicity and/or biokinetics of nanoparticulate and ionic silver. The results demonstrate subtle systemic changes involving selected oxidative stress-related genes in the liver and testis of animals exposed by pulmonary route to a low dose of AgNPs. These effects were apparently reversible as changes were observed at day 7 but not day 28. Recovery could possibly reflect either compensatory mechanism contrasting the initial toxicogenomic response to AgNPs or the silver removal from the tested organs. These findings may be of toxicological relevance in relation to possible health risks associated with occupational or consumer exposure to nanosilver
Domoic Acid
No full textIn the summer of 1961, thousands of sooty shearwaters (Puffinus griseus), a medium-large long-winged seabird that feeds on krill, squid, and fish, converged on the shores of North Monterey Bay, California. The birds were found regurgitating anchovies, crashing through glass windows, attacking people, shrieking vocalization uncommon for this species, and dying on the streets. 1 This episode inspired Hitchcock's 1963 horror film “The Birds” and has been later linked to domoic acid (DA) poisoning. 2 Since then episodes of disorientation, stereotypic scratching, seizures, and death associated with DA toxicity have been reported in California sea lions (Zalophus californianus), brown pelicans (Pelecanus occidentalis), Brant's cormorants (Phalacrocorax penicillatus), pygmy sperm whales (Kogia breviceps), dwarf sperm whales (Kogia sima), minke whales (Balaenoptera acutorostrata), and northern fur seals (Callorhinus ursinus). 3–10 The first documented episode of DA poisoning in humans occurred in Canada in 1987 when over 100 people developed gastrointestinal (vomiting, abdominal cramps, and diarrhoea) and/or neurological signs (headache, short-term memory loss, disorientation, and, in severe cases, seizures and coma) as well as fatalities after ingesting contaminated mussels (Mytilus edulis). 11 Because of the short-term memory loss observed in many of the affected patients, the condition was subsequently termed amnesic shellfish poisoning (ASP). This chapter reviews the chemical characteristics, occurrence, toxicokinetics, and mechanism of action of DA as well as the epidemiological data, clinical features, diagnosis, treatment, and prevention of ASP
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Effects on developmental exposure to Methylmercury and PCB153 on cerebral dopamine D1-like and D-2 lke receptors in weaning and pubertal rats
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