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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...

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Autores principales: Su, Zhonghao, Ye, Jin, Qin, Zhenxia, Ding, Xianting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
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.
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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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