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Toxicity Mechanisms (toxicity + mechanism)

Distribution by Scientific Domains

Chemistry	40%

Selected Abstracts

Nanobiomaterials and Nanoanalysis: Opportunities for Improving the Science to Benefit Biomedical Technologies,

ADVANCED MATERIALS, Issue 5 2008
W. Grainger
Abstract Nanomaterials advocated for biomedical applications must exhibit well-controlled surface properties to achieve optimum performance in complex biological or physiological fluids. Dispersed materials with extremely high specific surface areas require as extensive characterization as their macroscale biomaterials analogues. However, current literature is replete with many examples of nanophase materials, most notably nanoparticles, with little emphasis placed on reporting rigorous surface analysis or characterization, or in formal implementation of surface property standards needed to validate structure-property relationships for biomedical applications. Correlations of nanophase surface properties with their stability, toxicity and biodistributions are essential for in vivo applications. Surface contamination is likely, given their processing conditions and interfacial energies. Leaching adventitious adsorbates from high surface area nanomaterials is a possible toxicity mechanism. Polydimethylsiloxane (PDMS), long known as a ubiquitous contaminant in clean room conditions, chemical synthesis and microfabrication, remains a likely culprit in nanosystems fabrication, especially in synthesis, soft lithography and contact molding methods. New standards and expectations for analyzing the interfacial properties of nanoparticles and nano-fabricated technologies are required. Surface science analytical rigor similar to that applied to biomedical devices, nanophases in microelectronics and heterogeneous catalysts should serve as a model for nanomaterials characterization in biomedical technologies. [source]

Cytotoxic effects of polychlorinated biphenyl hydroquinone metabolites in rat hepatocytes

JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2010
Katie Chan
Abstract Polychlorinated biphenyls (PCBs) are persistent organic pollutants that exhibit various toxic effects in animals and exposed human populations. The molecular mechanisms of PCB toxicity have been attributed to the toxicological properties of its metabolites, such as hydroquinones, formed by cytochrome-P-450 oxidation. The effects of PCB hydroquinone metabolites towards freshly isolated rat hepatocytes were investigated. Hydroquinones can be oxidized to semiquinones and/or quinone metabolites. These metabolites can conjugate glutathione or can oxidize glutathione as a result of redox cycling. This depletes hepatocyte glutathione, which can inhibit cellular defence mechanisms, causing cell death and an increased susceptibility to oxidative stress. However in the following, glutathione-depleted hepatocytes became more resistant to the hydroquinone metabolites of PCBs. This suggested that their glutathione conjugates were toxic and that there was a third type of quinone toxicity mechanism which involved a hydrogen peroxide-accelerated autoxidation of the hydroquinones to form toxic electrophilic quinone and semiquinone,glutathione conjugates. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Quick assessment of cytotoxins effect on Daphnia magna using in vivo fluorescence microscopy

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2010
Vera V. Teplova
Abstract A novel approach to contaminant toxicity screening is proposed. The use of fluorescent microscopy with fluorescent dyes allows for assessing intoxication of Daphnia magna tissues, at various stages of exposure, to contaminants present in water. As shown, D. magna may not only be used as a test species in toxicity tests based on its lethality, but due to its translucency and application of fluorescent probes, separate steps of its intoxication and dying can be visualized. Using a variety of fluorescent probes, the present study also contributes to a better understanding of the toxicity mechanisms. Environ. Toxicol. Chem. 2010;29:1345,1348. © 2010 SETAC [source]

Oxidative stress as a multiple effector in Fanconi anaemia clinical phenotype

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2005
Giovanni Pagano
Abstract:, Fanconi anaemia (FA) is a genetic disease characterised by bone marrow failure with excess risk of myelogenous leukaemia and solid tumours. A widely accepted notion in FA research invokes a deficiency of response to DNA damage as the fundamental basis of the ,crosslinker sensitivity' observed in this disorder. However, such an isolated defect cannot readily account for the full cellular and clinical phenotype, which includes a number of other abnormalities, such as malformations, endocrinopathies, and typical skin spots. An extensive body of evidence pointing toward an involvement of oxidative stress in the FA phenotype includes the following: (i) In vitro and ex vivo abnormalities in a number of redox status endpoints; (ii) the functions of several FA proteins in protecting cells from oxidative stress; (iii) redox-related toxicity mechanisms of the xenobiotics evoking excess toxicity in FA cells. The clinical features in FA and the in vivo abnormalities of redox parameters are here reconsidered in view of the pleiotropic clinical phenotype and known biochemical and molecular links to an in vivo prooxidant state, which causes oxidative damage to biomolecules, resulting in an excessive number of acquired abnormalities that may overwhelm the cellular repair capacity rather than a primary deficiency in DNA repair. FA may thus represent a unique model disease in testing the integration between the acquisition of macromolecular damage as a result of oxidative stress and the ability of the mammalian cell to respond effectively to such damage. [source]

Pseudomonas putida KT2440 responds specifically to chlorophenoxy herbicides and their initial metabolites

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 11 2006
Dirk Benndorf Dr.
Abstract Pseudomonas putida,KT2440 is often used as a model to investigate toxicity mechanisms and adaptation to hazardous chemicals in bacteria. The objective of this paper was to test the impact of the chlorophenoxy herbicides 2,4-dichlorophenoxyacetic acid,(2,4-D) and 2-(2,4-dichlorophenoxy)propanoic acid,(DCPP) and their metabolites 2,4-dichlorophenol,(DCP) and 3,5-dichlorocatechol,(DCC), on protein expression patterns and physiological parameters. Both approaches showed that DCC has a different mode of action and induces different responses than DCPP, 2,4-D and DCP. DCC was the most toxic compound and was active as an uncoupler of oxidative phosphorylation. It repressed the synthesis of ferric uptake regulator (Fur)-dependent proteins, e.g. fumarase,C and L -ornithine N5-oxygenase, which are involved in oxidative stress response and iron uptake. DCPP, 2,4-D and DCP were less toxic than DCC. They disturbed oxidative phosphorylation to a lesser extent by a yet unknown mechanism. Furthermore, they repressed enzymes of energy-consuming biosynthetic pathways and induced membrane transporters for organic substrates. A TolC homologue component of multidrug resistance transporters was found to be induced, which is probably involved in the removal of lipophilic compounds from membranes. [source]