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  • 1
    ISSN: 1432-0738
    Keywords: Key words 1 ; 1 ; 2-Trichloroethene ; S-(1 ; 2-Dichlorovinyl)-L-cysteine ; S-(2 ; 2-Dichlorovinyl)-L-cysteine ; Isolated perfused rat kidney ; Nephrotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The nephrotoxic effects of the two isomers S-(1,2-dichlorovinyl)-L-cysteine (1,2-DCVC) and S-(2,2-dichlorovinyl)-L-cysteine (2,2-DCVC) were investigated comparatively in the isolated perfused rat kidney with two different treatment regimens. In the first approach, the kidneys were exposed to the test compounds dissolved in the perfusion media after removal from the animal. In the second approach the test compounds were administered to rats in vivo and the nephrotoxicity was assessed in the isolated perfused kidney 6 h and 18 h post-treatment. The vicinal isomer 1,2-DCVC produced concentration- and time-dependent nephrotoxicity with both treatment regimens, as indicated by the impairment of glucose reabsorption, the increase of protein excretion and of γ-glutamyltransferase and alkaline phosphatase activities in urine. In contrast to the marked toxicity observed after in vivo and in vitro administration of 1,2-DCVC, the geminal isomer, 2,2-DCVC, was not nephrotoxic at all concentrations (0.5 and 2.5 mM in vitro, 40 and 70 mg/kg in vivo) investigated.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-6822
    Keywords: c-fos ; c-myc ; growth factors ; LLC-PK1 cells ; 12-O-tetradecanoylphorbolacetate ; S-(1,2-dichlorovinyl)-L-cysteine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Previous studies in kldney cells showed that S-(l,2-dichloroviny1)-L-cysteitle (DCVC) induces both direct DNA damage and DNA double-strand breaks by activation of Ca2+-dependent endonucleases. The objective of this study was to investigate the effects of DCVC on the expression of the protooncogenes c-fos and c-myc in cultured kidney cells (LLC-PK1). Supplementation of the incubation medium with 10% FCS after 24 hr incubation in 0.2% FCS resulted in a clear, but comparatively weak induction of the expression of c-fos and c-myc in LLC-PK1 cells. Addition of 500 pm DCVC to the high serum incubation medium induced a further three-jold increase of the transcript levels. A similar increase in the absolute amount of c-fos mRNA was induced by a mixture of growth factors (epidermal growth factorlinsulini transferrin) and of c-myc mRNA with 12-0-tetradecanoylphorbolacetate. However, the kinetics of gene expression were different. In the presence of DCVC the expression of c-fos and c-myc increased continuously in a time-dependent manner during the entire incubatiorl period. In contrast, with growth factors and 12-0-tetradecanoyl-phorbolacetate the maximum transcript levels were detected after 0.5 hr (c-fos) and 1 hr (c-myc), respectively; thereafter, a slight decrease was observed up to the end of the incubakion lime.
    Type of Medium: Electronic Resource
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