Toxicodynamic Evaluation of a Cisplatin-Chondroitin Sulfate Complex Using a Perfused Kidney and Human Proximal Tubular Cells
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...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
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Informa Healthcare
2011
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| Online Access: | http://hdl.handle.net/20.500.11937/44056 |
| _version_ | 1848756888513019904 |
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| author | Zhang, J. Kadowaki, D. Nonoguchi, H. Hirata, S. Seo, H. Imai, T. Suenaga, A. Chuang, Victor Otagiri, M. |
| author_facet | Zhang, J. Kadowaki, D. Nonoguchi, H. Hirata, S. Seo, H. Imai, T. Suenaga, A. Chuang, Victor Otagiri, M. |
| author_sort | Zhang, J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T09:19:21Z |
| format | Journal Article |
| id | curtin-20.500.11937-44056 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:19:21Z |
| publishDate | 2011 |
| publisher | Informa Healthcare |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-440562017-09-13T16:05:30Z Toxicodynamic Evaluation of a Cisplatin-Chondroitin Sulfate Complex Using a Perfused Kidney and Human Proximal Tubular Cells Zhang, J. Kadowaki, D. Nonoguchi, H. Hirata, S. Seo, H. Imai, T. Suenaga, A. Chuang, Victor Otagiri, M. nephrotoxicity human proximal tubular cells complexation Chondroitin sulfate cytotoxicity cisplatin perfused kidney 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. 2011 Journal Article http://hdl.handle.net/20.500.11937/44056 10.3109/0886022X.2011.585266 Informa Healthcare unknown |
| spellingShingle | nephrotoxicity human proximal tubular cells complexation Chondroitin sulfate cytotoxicity cisplatin perfused kidney Zhang, J. Kadowaki, D. Nonoguchi, H. Hirata, S. Seo, H. Imai, T. Suenaga, A. Chuang, Victor Otagiri, M. Toxicodynamic Evaluation of a Cisplatin-Chondroitin Sulfate Complex Using a Perfused Kidney and Human Proximal Tubular Cells |
| title | Toxicodynamic Evaluation of a Cisplatin-Chondroitin Sulfate Complex Using a Perfused Kidney and Human Proximal Tubular Cells |
| title_full | Toxicodynamic Evaluation of a Cisplatin-Chondroitin Sulfate Complex Using a Perfused Kidney and Human Proximal Tubular Cells |
| title_fullStr | Toxicodynamic Evaluation of a Cisplatin-Chondroitin Sulfate Complex Using a Perfused Kidney and Human Proximal Tubular Cells |
| title_full_unstemmed | Toxicodynamic Evaluation of a Cisplatin-Chondroitin Sulfate Complex Using a Perfused Kidney and Human Proximal Tubular Cells |
| title_short | Toxicodynamic Evaluation of a Cisplatin-Chondroitin Sulfate Complex Using a Perfused Kidney and Human Proximal Tubular Cells |
| title_sort | toxicodynamic evaluation of a cisplatin-chondroitin sulfate complex using a perfused kidney and human proximal tubular cells |
| topic | nephrotoxicity human proximal tubular cells complexation Chondroitin sulfate cytotoxicity cisplatin perfused kidney |
| url | http://hdl.handle.net/20.500.11937/44056 |