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    Toxicodynamic Evaluation of a Cisplatin-Chondroitin Sulfate Complex Using a Perfused Kidney and Human Proximal Tubular Cells

    Access Status
    Open access via publisher
    Authors
    Zhang, J.
    Kadowaki, D.
    Nonoguchi, H.
    Hirata, S.
    Seo, H.
    Imai, T.
    Suenaga, A.
    Chuang, Victor
    Otagiri, M.
    Date
    2011
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Zhang, Jing-Shi and Kadowaki, Daisuke and Nonoguchi, Hiroshi and Hirata, Sumio and Seo, Hakaru and Imai, Teruko and Suenaga, Ayaka and Chuang, Victor Tuan Giam and Otagiri, Masaki. 2011. Toxicodynamic Evaluation of a Cisplatin-Chondroitin Sulfate Complex Using a Perfused Kidney and Human Proximal Tubular Cells. Renal Failure. 33 (6): pp. 609-614.
    Source Title
    Renal Failure
    DOI
    10.3109/0886022X.2011.585266
    ISSN
    1525-6049
    School
    School of Pharmacy
    URI
    http://hdl.handle.net/20.500.11937/44056
    Collection
    • Curtin Research Publications
    Abstract

    Cisplatin (CDDP) is an anticancer drug. The clinical limitations associated with CDDP have stimulated the development of macromolecular drug-carrier systems, in attempts to decrease its toxicity. A complex (CDDP-CSA-23) between CDDP and chondroitin sulfate (CSA), a natural polysaccharide with a mean molecular weight of 23 kDa, proved to have the same anticancer activity as CDDP. A toxicodynamic study was performed on perfused kidneys to determine the effect of CDDP-CSA-23 on renal functions and the extent of platinum accumulation. The results showed that CDDP-CSA-23 attenuates the reduction in urine flow and creatinine clearance induced by CDDP. Moreover, significantly lower amounts of platinum were excreted into the urine in the case of CDDP-CSA-23, compared with CDDP alone. Meanwhile, CDDP-CSA-23 effectively retarded the rapid perfusion of platinum into kidney tissues, as occurs when CDDP is being perfused alone.The cytoprotective effects of CDDP-CSA on human proximal tubular (HK-2) cells were examined by measuring the growth of HK-2 cells in the presence of CDDP or CDDP-CSA-23. Interestingly, CDDP-CSA-23 was found to have a significantly reduced cytotoxicity, compared to CDDP. These results suggest that CDDP-CSA-23 greatly decreased the negative effects of CDDP on glomerular filtration and tubular transport in kidneys at early stages of its administration.

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