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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...

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Autores principales: Wang, Runming, Wang, Suyu, Chan, Shing, Wang, Yuchuan, Zhang, Yufeng, Zuo, Zhong, Chi-Fung Chan, Godfrey, Li, Hongyan, Sun, Hongzhe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
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.
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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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