Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating inflammation and SIRT6/TNF-α signaling
Despite cisplatin has been widely used in the treatment of various cancers, the noteworthy nephrotoxicity greatly constrained its clinical value. For this reason, finding novel targeted therapies to attenuate the nephrotoxicity of cisplatin should be pretty significant. Our previous study found that...
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Tsinghua University Press
2023-11-01
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| Series: | Food Science and Human Wellness |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213453023000952 |
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| author | Yuqi Gao Kezheng Peng Yida Wang Yannan Guo Chenye Zeng Rui Hua Qingfei Liu Xue Li Ying Qiu Zhao Wang |
| author_facet | Yuqi Gao Kezheng Peng Yida Wang Yannan Guo Chenye Zeng Rui Hua Qingfei Liu Xue Li Ying Qiu Zhao Wang |
| author_sort | Yuqi Gao |
| collection | DOAJ |
| description | Despite cisplatin has been widely used in the treatment of various cancers, the noteworthy nephrotoxicity greatly constrained its clinical value. For this reason, finding novel targeted therapies to attenuate the nephrotoxicity of cisplatin should be pretty significant. Our previous study found that histone deacetylase sirtuin 6 (SIRT6) could be an ideal target for the treatment of cisplatin-induced acute kidney injury. In this study, we explored the protective effects of ellagic acid, a natural polyphenol compound that activates SIRT6, on cisplatin-induced nephrotoxicity. Pre-treatment of ellagic acid attenuated cytotoxicity of cisplatin in primary renal cells and TCMK-1 cells. Moreover, ellagic acid ameliorated renal dysfunction, apoptosis and fibrosis induced by cisplatin in mice. Furthermore, ellagic acid reduced nephrotoxicity-associated inflammatory factor interleukin (IL)-1β and IL-6 expression both in vitro and in vivo. Mechanistically, ellagic acid reversed cisplatin-reduced SIRT6 expression and diminished cisplatin-induced tumor necrosis factor (TNF)-α expression. And SIRT6 knockdown abrogated the protective effects of ellagic acid on cisplatin-induced cell apoptosis, indicating the renal-protective effects of ellagic acid are mainly dependent on ellagic acid-mediated SIRT6 activation. Our results provide preclinical rationale for using ellagic acid as a feasible and promising agent to ameliorate cisplatin-induced acute kidney injury, and support ellagic acid as a potential adjunctive therapy for future cancer treatment. |
| format | Article |
| id | doaj-art-48ac0ae672da48009febd42d4c36ec1a |
| institution | Kabale University |
| issn | 2213-4530 |
| language | English |
| publishDate | 2023-11-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-48ac0ae672da48009febd42d4c36ec1a2025-02-03T05:55:57ZengTsinghua University PressFood Science and Human Wellness2213-45302023-11-0112622322241Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating inflammation and SIRT6/TNF-α signalingYuqi Gao0Kezheng Peng1Yida Wang2Yannan Guo3Chenye Zeng4Rui Hua5Qingfei Liu6Xue Li7Ying Qiu8Zhao Wang9The Ministry of Education Key Laboratory of Protein Science, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, ChinaThe Ministry of Education Key Laboratory of Protein Science, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, ChinaThe Ministry of Education Key Laboratory of Protein Science, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, ChinaThe Ministry of Education Key Laboratory of Protein Science, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, ChinaThe Ministry of Education Key Laboratory of Protein Science, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, ChinaThe Ministry of Education Key Laboratory of Protein Science, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, ChinaThe Ministry of Education Key Laboratory of Protein Science, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, ChinaSchool of Medicine, Tsinghua University, Beijing 100084, ChinaSchool of Medicine, Tsinghua University, Beijing 100084, ChinaThe Ministry of Education Key Laboratory of Protein Science, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China; Corresponding author at: School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.Despite cisplatin has been widely used in the treatment of various cancers, the noteworthy nephrotoxicity greatly constrained its clinical value. For this reason, finding novel targeted therapies to attenuate the nephrotoxicity of cisplatin should be pretty significant. Our previous study found that histone deacetylase sirtuin 6 (SIRT6) could be an ideal target for the treatment of cisplatin-induced acute kidney injury. In this study, we explored the protective effects of ellagic acid, a natural polyphenol compound that activates SIRT6, on cisplatin-induced nephrotoxicity. Pre-treatment of ellagic acid attenuated cytotoxicity of cisplatin in primary renal cells and TCMK-1 cells. Moreover, ellagic acid ameliorated renal dysfunction, apoptosis and fibrosis induced by cisplatin in mice. Furthermore, ellagic acid reduced nephrotoxicity-associated inflammatory factor interleukin (IL)-1β and IL-6 expression both in vitro and in vivo. Mechanistically, ellagic acid reversed cisplatin-reduced SIRT6 expression and diminished cisplatin-induced tumor necrosis factor (TNF)-α expression. And SIRT6 knockdown abrogated the protective effects of ellagic acid on cisplatin-induced cell apoptosis, indicating the renal-protective effects of ellagic acid are mainly dependent on ellagic acid-mediated SIRT6 activation. Our results provide preclinical rationale for using ellagic acid as a feasible and promising agent to ameliorate cisplatin-induced acute kidney injury, and support ellagic acid as a potential adjunctive therapy for future cancer treatment.http://www.sciencedirect.com/science/article/pii/S2213453023000952Ellagic acidNephrotoxicityCisplatinSIRT6TNF-α |
| spellingShingle | Yuqi Gao Kezheng Peng Yida Wang Yannan Guo Chenye Zeng Rui Hua Qingfei Liu Xue Li Ying Qiu Zhao Wang Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating inflammation and SIRT6/TNF-α signaling Food Science and Human Wellness Ellagic acid Nephrotoxicity Cisplatin SIRT6 TNF-α |
| title | Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating inflammation and SIRT6/TNF-α signaling |
| title_full | Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating inflammation and SIRT6/TNF-α signaling |
| title_fullStr | Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating inflammation and SIRT6/TNF-α signaling |
| title_full_unstemmed | Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating inflammation and SIRT6/TNF-α signaling |
| title_short | Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating inflammation and SIRT6/TNF-α signaling |
| title_sort | ellagic acid ameliorates cisplatin induced acute kidney injury by regulating inflammation and sirt6 tnf α signaling |
| topic | Ellagic acid Nephrotoxicity Cisplatin SIRT6 TNF-α |
| url | http://www.sciencedirect.com/science/article/pii/S2213453023000952 |
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