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

Autor: Zhang, Jing-Shi, Kadowaki, Daisuke, Nonoguchi, Hiroshi, Hirata, Sumio, Seo, Hakaru, Imai, Teruko, Suenaga, Ayaka, Giam Chuang, Victor Tuan, Otagiri, Masaki
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Zdroj: Renal Failure; 2011, Vol. 33 Issue 6, p609-614, 6p, 4 Graphs
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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