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  • 1
    Electronic Resource
    Electronic Resource
    Effects of cysteine derivatives of styrene on the transport ofp-aminohippurate ion in renal plasma membrane vesicles (1991)
    Springer
    Archives of toxicology 65 (1991), S. 366-372 
    Details
    ISSN: 1432-0738
    Keywords: S-1/2-(Phenyl-hydroxyethyl)cysteine ; Organic anion transport ; Brush border membrane vesicles ; Basolateral membrane vesicles ; Nephrotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of cysteine conjugates of styrene, e.g. S-1/2-(phenyl-hydroxyethyl) cysteine (PEC) and its N-acetyl derivative (NAPEC) on the transport ofp-aminohippurate (PAH) ion in plasma membranes were studied in vitro using isolated rat renal brush-border membrane (BBM) and basolateral membrane (BLM) vesicles. The uptake of PAH was significantly inhibited by both PEC and NAPEC in both the membrane vesicles, as verified by decrease of the membrane/medium concentration ratio of PAH as the concentration of either PEC or NAPEC in the medium increased. These results show that both PEC and NAPEC are capable of interfering with the accumulation of PAH (a model organic anion for renal tubular transport system) by both energy-independent and energy-dependent carrier-mediated transport processes. The inhibition of PAH uptake in BBM vesicles due to 10 mM PEC or NAPEC was found to be nearly competitive, almost similar to probenecid, whereas in BLM vesicles such inhibition was found to be partially noncompetitive, as verified by the double reciprocal plots. Both PEC and NAPEC showed dose-dependent inhibition of the specific activity of the marker enzyme in each membrane, e. g. gamma-glutamyl transferase in BBM and Na+-K+-ATPase in BLM vesicles. However, no such inhibition was noticed with probenecid. The in vitro pretreatment with probenecid prevented the inhibition of gamma-glutamyl transferase activity in BBM due to PEC or NAPEC, but such was not the case for the Na+-K+-ATPase activity in BLM. In conclusion, the data suggest that the transport of cysteine or N-acetylcysteine conjugates of styrene by renal proximal tubular cells across both the membrane vesicles accompanied by the inhibition of the membrane-specific enzymes may lead to cellular dysfunction and consequently to the initial development of their nephrotoxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02284258
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  • 2
    Electronic Resource
    Electronic Resource
    Absence of genotoxic effects of nonasbestos mineral fibers (1985)
    Springer
    Cell biology and toxicology 1 (1985), S. 23-32 
    Details
    ISSN: 1573-6822
    Keywords: genotoxicity ; UDS ; hepatocytes ; attapulgite ; xonotlite ; sepiolite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The biological activity of natural and synthetic mineral fibers has been examined. Natural attapulgite [(Mg, Al)2Si4O10(OH).4H20], synthetic xonotlite [Ca3Si3O8(OH)2] and natural sepiolite [Mg2Si3O8.2H2O] were selected. Genotoxic effects were investigated by means of a well established cellular model based upon the measurement of unscheduled DNA synthesis (UDS) in rat hepatocytes in primary culture. The intrinsic capacity of the fibers (1 and 10 µ/ml) to induce UDS was first tested. None of the fiber types showed detectable UDS-eliciting activity. Also, the possible modulation of the cellular response to genotoxic agents by the materials was examined by exposing the cells to mixtures of 2-acetylaminofluorene (AAF) (0.05 and 0.25 µg/ml) and fibers (1 and 10 µg/ml). In these experiments, the UDS response was significantly diminished in the presence of xonotlite. This phenomenon may reflect changes in the uptake and/or metabolism of AAF or may result from an inhibition of DNA repair processes, the latter suggesting a possible cocarcinogenic potential for this synthetic silicate. These results point to the immediate necessity of studying more extensively the biological effects of fibrous materials that can be used as substitutes for asbestos.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00717788
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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