Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9035262 | Toxicology | 2005 | 15 Pages |
Abstract
Tubular epithelium represents the primary target of mercuric ions (Hg2+) nephrotoxicity. Although widely investigated, the mechanisms of Hg2+ cell uptake, accumulation and excretion all along the nephron remain largely unknown. In the present study, native distal tubular-derived Madin-Darby canine kidney (MDCK) cells exposed to subcytotoxic (micromolar) HgCl2 concentrations were used for investigating specific mechanisms involved in the tubular response to toxic metals. Inductively coupled plasma-mass spectrometry (ICP-MS) was firstly used for assessing HgCl2 solubility and then for quantifying Hg2+ cell uptake. Exposed to HgCl2, MDCK cells showed a rapid, but transient, Hg2+ accumulation. The metallic cation was found to affect cell density and morphology, being these effects related to the dose and the time of exposure. In parallel, an Hg2+-induced up-regulation of endogenous MRP1 and MRP2 export pumps, a significant HgCl2-dependent induction of protective cellular thiols and an increase in the glutathione conjugates metabolism were also observed. The functional suppression of MRPs activity, obtained by MK-571 treatment, increased the Hg2+ cell content and the sensitivity of MDCK cells to HgCl2. Our results demonstrate that, in MDCK cells, inorganic Hg2+ promotes the activation of specific detoxifying pathways that may, at least partly, depend on the activity of MRP transporters.
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Authors
Maria Francesca Aleo, Fausta Morandini, Francesca Bettoni, Roberta Giuliani, Francesca Rovetta, Nathalie Steimberg, Pietro Apostoli, Giovanni Parrinello, Giovanna Mazzoleni,