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Protective effects of madecassoside against Doxorubicin induced nephrotoxicity in vivo and in vitro
Madecassoside (MA), a triterpenoid saponin isolated from C. asitica, exerts various pharmacological activity including antioxidative and antinflammatory. Doxorubicin (DOX), a common chemotherapeutic drug, has been reported to induce numerous toxic side effects including renal-toxicity. We hypothesiz...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677317/ https://www.ncbi.nlm.nih.gov/pubmed/26658818 http://dx.doi.org/10.1038/srep18314 |
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author | Su, Zhonghao Ye, Jin Qin, Zhenxia Ding, Xianting |
author_facet | Su, Zhonghao Ye, Jin Qin, Zhenxia Ding, Xianting |
author_sort | Su, Zhonghao |
collection | PubMed |
description | Madecassoside (MA), a triterpenoid saponin isolated from C. asitica, exerts various pharmacological activity including antioxidative and antinflammatory. Doxorubicin (DOX), a common chemotherapeutic drug, has been reported to induce numerous toxic side effects including renal-toxicity. We hypothesized that MA administration may decrease renal-toxicity caused by DOX. In this study, we investigated this hypothesis by introducing MA and DOX into the culture of Human Proximal Tubule Cells HK-2 and mice model. Our in vivo study demonstrated that MA (12 mg/kg), treatment for two weeks attenuated DOX-induced renal injury via protecting renal function, recovering antioxidant enzyme activity, inhibiting Bax, p-ERK1/2, NF-κB p65, iNOS expression and increasing Bcl-2 expression. Similar findings were obtained in our in vitro studies with treatment of DOX and/or MA. Further studies with application of iNOS inhibitor and ERK1/2 kinase inhibitor indicated that the inhibitory effects of MA on DOX-induced apoptosis and inflammation might be mediated by the suppression of the activation of cleaved caspase-3, ERK1/2 pathways, NF-κB p65 and NO production. These results suggest that MA is a promising protective agent for DOX-induced renal toxicity and can be a potential candidate to protect against renal toxicity in DOX-treated cancer patients. |
format | Online Article Text |
id | pubmed-4677317 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46773172015-12-17 Protective effects of madecassoside against Doxorubicin induced nephrotoxicity in vivo and in vitro Su, Zhonghao Ye, Jin Qin, Zhenxia Ding, Xianting Sci Rep Article Madecassoside (MA), a triterpenoid saponin isolated from C. asitica, exerts various pharmacological activity including antioxidative and antinflammatory. Doxorubicin (DOX), a common chemotherapeutic drug, has been reported to induce numerous toxic side effects including renal-toxicity. We hypothesized that MA administration may decrease renal-toxicity caused by DOX. In this study, we investigated this hypothesis by introducing MA and DOX into the culture of Human Proximal Tubule Cells HK-2 and mice model. Our in vivo study demonstrated that MA (12 mg/kg), treatment for two weeks attenuated DOX-induced renal injury via protecting renal function, recovering antioxidant enzyme activity, inhibiting Bax, p-ERK1/2, NF-κB p65, iNOS expression and increasing Bcl-2 expression. Similar findings were obtained in our in vitro studies with treatment of DOX and/or MA. Further studies with application of iNOS inhibitor and ERK1/2 kinase inhibitor indicated that the inhibitory effects of MA on DOX-induced apoptosis and inflammation might be mediated by the suppression of the activation of cleaved caspase-3, ERK1/2 pathways, NF-κB p65 and NO production. These results suggest that MA is a promising protective agent for DOX-induced renal toxicity and can be a potential candidate to protect against renal toxicity in DOX-treated cancer patients. Nature Publishing Group 2015-12-14 /pmc/articles/PMC4677317/ /pubmed/26658818 http://dx.doi.org/10.1038/srep18314 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Su, Zhonghao Ye, Jin Qin, Zhenxia Ding, Xianting Protective effects of madecassoside against Doxorubicin induced nephrotoxicity in vivo and in vitro |
title | Protective effects of madecassoside against Doxorubicin induced nephrotoxicity in vivo and in vitro |
title_full | Protective effects of madecassoside against Doxorubicin induced nephrotoxicity in vivo and in vitro |
title_fullStr | Protective effects of madecassoside against Doxorubicin induced nephrotoxicity in vivo and in vitro |
title_full_unstemmed | Protective effects of madecassoside against Doxorubicin induced nephrotoxicity in vivo and in vitro |
title_short | Protective effects of madecassoside against Doxorubicin induced nephrotoxicity in vivo and in vitro |
title_sort | protective effects of madecassoside against doxorubicin induced nephrotoxicity in vivo and in vitro |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677317/ https://www.ncbi.nlm.nih.gov/pubmed/26658818 http://dx.doi.org/10.1038/srep18314 |
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