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Bismuth Porphyrin Antagonizes Cisplatin-Induced Nephrotoxicity via Unexpected Metallothionein-Independent Mechanisms
Cisplatin (CDDP) has been a highly successful anticancer drug in cancer therapy; however, its further application suffers severe nephrotoxicity. Herein, we identify bismuth tetraphenylporphyrinate [Bi(TPP)] as a potent protective agent against CDDP-induced nephrotoxicity. Bi(TPP) attenuates CDDP-ind...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191608/ https://www.ncbi.nlm.nih.gov/pubmed/32353763 http://dx.doi.org/10.1016/j.isci.2020.101054 |
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author | Wang, Runming Wang, Suyu Chan, Shing Wang, Yuchuan Zhang, Yufeng Zuo, Zhong Chi-Fung Chan, Godfrey Li, Hongyan Sun, Hongzhe |
author_facet | Wang, Runming Wang, Suyu Chan, Shing Wang, Yuchuan Zhang, Yufeng Zuo, Zhong Chi-Fung Chan, Godfrey Li, Hongyan Sun, Hongzhe |
author_sort | Wang, Runming |
collection | PubMed |
description | Cisplatin (CDDP) has been a highly successful anticancer drug in cancer therapy; however, its further application suffers severe nephrotoxicity. Herein, we identify bismuth tetraphenylporphyrinate [Bi(TPP)] as a potent protective agent against CDDP-induced nephrotoxicity. Bi(TPP) attenuates CDDP-induced acute kidney injury and prevents the death of mice exposed to a lethal dose of CDDP. The protective potency of bismuth porphyrin complexes could be optimized by varying lipophilic TPP ligands with ideal ClogP values of 8–14. Unexpectedly, Bi(TPP) exhibited a protective role via metallothionein-independent pathways, i.e., maintenance of redox homeostasis and energy supplement, elimination of accumulated platinum in the kidney, and inactivation of caspases cascade in apoptotic pathway. Significantly, Bi(TPP) does not compromise the antitumor activity of CDDP in the orthotopic tumor xenograft mouse model. These findings suggest that Bi(TPP) could be incorporated into current CDDP-based cancer therapy as a nephroprotective agent. |
format | Online Article Text |
id | pubmed-7191608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-71916082020-05-05 Bismuth Porphyrin Antagonizes Cisplatin-Induced Nephrotoxicity via Unexpected Metallothionein-Independent Mechanisms Wang, Runming Wang, Suyu Chan, Shing Wang, Yuchuan Zhang, Yufeng Zuo, Zhong Chi-Fung Chan, Godfrey Li, Hongyan Sun, Hongzhe iScience Article Cisplatin (CDDP) has been a highly successful anticancer drug in cancer therapy; however, its further application suffers severe nephrotoxicity. Herein, we identify bismuth tetraphenylporphyrinate [Bi(TPP)] as a potent protective agent against CDDP-induced nephrotoxicity. Bi(TPP) attenuates CDDP-induced acute kidney injury and prevents the death of mice exposed to a lethal dose of CDDP. The protective potency of bismuth porphyrin complexes could be optimized by varying lipophilic TPP ligands with ideal ClogP values of 8–14. Unexpectedly, Bi(TPP) exhibited a protective role via metallothionein-independent pathways, i.e., maintenance of redox homeostasis and energy supplement, elimination of accumulated platinum in the kidney, and inactivation of caspases cascade in apoptotic pathway. Significantly, Bi(TPP) does not compromise the antitumor activity of CDDP in the orthotopic tumor xenograft mouse model. These findings suggest that Bi(TPP) could be incorporated into current CDDP-based cancer therapy as a nephroprotective agent. Elsevier 2020-04-12 /pmc/articles/PMC7191608/ /pubmed/32353763 http://dx.doi.org/10.1016/j.isci.2020.101054 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Wang, Runming Wang, Suyu Chan, Shing Wang, Yuchuan Zhang, Yufeng Zuo, Zhong Chi-Fung Chan, Godfrey Li, Hongyan Sun, Hongzhe Bismuth Porphyrin Antagonizes Cisplatin-Induced Nephrotoxicity via Unexpected Metallothionein-Independent Mechanisms |
title | Bismuth Porphyrin Antagonizes Cisplatin-Induced Nephrotoxicity via Unexpected Metallothionein-Independent Mechanisms |
title_full | Bismuth Porphyrin Antagonizes Cisplatin-Induced Nephrotoxicity via Unexpected Metallothionein-Independent Mechanisms |
title_fullStr | Bismuth Porphyrin Antagonizes Cisplatin-Induced Nephrotoxicity via Unexpected Metallothionein-Independent Mechanisms |
title_full_unstemmed | Bismuth Porphyrin Antagonizes Cisplatin-Induced Nephrotoxicity via Unexpected Metallothionein-Independent Mechanisms |
title_short | Bismuth Porphyrin Antagonizes Cisplatin-Induced Nephrotoxicity via Unexpected Metallothionein-Independent Mechanisms |
title_sort | bismuth porphyrin antagonizes cisplatin-induced nephrotoxicity via unexpected metallothionein-independent mechanisms |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191608/ https://www.ncbi.nlm.nih.gov/pubmed/32353763 http://dx.doi.org/10.1016/j.isci.2020.101054 |
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