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Renal protective effect of polysulfide in cisplatin-induced nephrotoxicity
Cisplatin is a major chemotherapeutic drug for solid tumors whereas it may lead to severe nephrotoxicity. Despite decades of efforts, effective therapies remain largely lacking for this disease. In the current research, we investigated the therapeutic effect of hydrogen polysulfide, a novel hydrogen...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881418/ https://www.ncbi.nlm.nih.gov/pubmed/29413963 http://dx.doi.org/10.1016/j.redox.2018.01.012 |
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author | Cao, Xu Nie, Xiaowei Xiong, Siping Cao, Lei Wu, Zhiyuan Moore, Philip K. Bian, Jin-Song |
author_facet | Cao, Xu Nie, Xiaowei Xiong, Siping Cao, Lei Wu, Zhiyuan Moore, Philip K. Bian, Jin-Song |
author_sort | Cao, Xu |
collection | PubMed |
description | Cisplatin is a major chemotherapeutic drug for solid tumors whereas it may lead to severe nephrotoxicity. Despite decades of efforts, effective therapies remain largely lacking for this disease. In the current research, we investigated the therapeutic effect of hydrogen polysulfide, a novel hydrogen sulfide (H(2)S) derived signaling molecule, in cisplatin nephrotoxicity and the mechanisms involved. Our results showed that polysulfide donor Na(2)S(4) ameliorated cisplatin-caused renal toxicity in vitro and in vivo through suppressing intracellular reactive oxygen species (ROS) generation and downstream mitogen-activated protein kinases (MAPKs) activation. Additionally, polysulfide may inhibit ROS production by simultaneously lessening the activation of NADPH oxidase and inducing nucleus translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in RPT cells. Interestingly, polysulfide possesses anti-cancer activity and is able to add on more anti-cancer effect to cisplatin in non-small cell lung cancer (NSCLC) cell lines. Moreover, we observed that the number of sulfur atoms in polysulfide well reflected the efficacy of these molecules not only in cell protection but also cancer inhibition which may serve as a guide for further development of polysulfide donors for pharmaceutical usage. Taken together, our study suggests that polysulfide may be a novel and promising therapeutic agent to prevent cisplatin-induced nephrotoxicity. |
format | Online Article Text |
id | pubmed-5881418 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-58814182018-04-04 Renal protective effect of polysulfide in cisplatin-induced nephrotoxicity Cao, Xu Nie, Xiaowei Xiong, Siping Cao, Lei Wu, Zhiyuan Moore, Philip K. Bian, Jin-Song Redox Biol Research Paper Cisplatin is a major chemotherapeutic drug for solid tumors whereas it may lead to severe nephrotoxicity. Despite decades of efforts, effective therapies remain largely lacking for this disease. In the current research, we investigated the therapeutic effect of hydrogen polysulfide, a novel hydrogen sulfide (H(2)S) derived signaling molecule, in cisplatin nephrotoxicity and the mechanisms involved. Our results showed that polysulfide donor Na(2)S(4) ameliorated cisplatin-caused renal toxicity in vitro and in vivo through suppressing intracellular reactive oxygen species (ROS) generation and downstream mitogen-activated protein kinases (MAPKs) activation. Additionally, polysulfide may inhibit ROS production by simultaneously lessening the activation of NADPH oxidase and inducing nucleus translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in RPT cells. Interestingly, polysulfide possesses anti-cancer activity and is able to add on more anti-cancer effect to cisplatin in non-small cell lung cancer (NSCLC) cell lines. Moreover, we observed that the number of sulfur atoms in polysulfide well reflected the efficacy of these molecules not only in cell protection but also cancer inhibition which may serve as a guide for further development of polysulfide donors for pharmaceutical usage. Taken together, our study suggests that polysulfide may be a novel and promising therapeutic agent to prevent cisplatin-induced nephrotoxicity. Elsevier 2018-02-02 /pmc/articles/PMC5881418/ /pubmed/29413963 http://dx.doi.org/10.1016/j.redox.2018.01.012 Text en © 2018 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 | Research Paper Cao, Xu Nie, Xiaowei Xiong, Siping Cao, Lei Wu, Zhiyuan Moore, Philip K. Bian, Jin-Song Renal protective effect of polysulfide in cisplatin-induced nephrotoxicity |
title | Renal protective effect of polysulfide in cisplatin-induced nephrotoxicity |
title_full | Renal protective effect of polysulfide in cisplatin-induced nephrotoxicity |
title_fullStr | Renal protective effect of polysulfide in cisplatin-induced nephrotoxicity |
title_full_unstemmed | Renal protective effect of polysulfide in cisplatin-induced nephrotoxicity |
title_short | Renal protective effect of polysulfide in cisplatin-induced nephrotoxicity |
title_sort | renal protective effect of polysulfide in cisplatin-induced nephrotoxicity |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881418/ https://www.ncbi.nlm.nih.gov/pubmed/29413963 http://dx.doi.org/10.1016/j.redox.2018.01.012 |
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