Isorhamnetin alleviates cisplatin-induced acute kidney injury via enhancing fatty acid oxidation
Cisplatin is an effective chemotherapy drug widely used in the treatment of various solid tumors. However, the clinical usage of cisplatin is limited by its nephrotoxicity. Isorhamnetin, a natural flavanol compound, displays remarkable pharmacological effects, including anti-inflammatory and anti-ox...
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description | Cisplatin is an effective chemotherapy drug widely used in the treatment of various solid tumors. However, the clinical usage of cisplatin is limited by its nephrotoxicity. Isorhamnetin, a natural flavanol compound, displays remarkable pharmacological effects, including anti-inflammatory and anti-oxidation. In this study, we aimed to investigate the potential of isorhamnetin in alleviating acute kidney injury induced by cisplatin. In vitro study showed that isorhamnetin significantly suppressed the cytotoxic effects of cisplatin on human tubular epithelial cells. Furthermore, isorhamnetin exerted significantly inhibitory effects on cisplatin-induced apoptosis and inflammatory response. In acute kidney injury mice induced by a single intraperitoneal injection with 20 mg/kg cisplatin, oral administration of isorhamnetin two days before or 2 h after cisplatin injection effectively ameliorated renal function and renal tubule injury. Transcriptomics RNA-seq analysis of the mice kidney tissues suggested that isorhamnetin treatment may protect against cisplatin-induced nephrotoxicity via PGC-1α mediated fatty acid oxidation. Isorhamnetin achieved significant enhancements in the lipid clearance, ATP level, as well as the expression of PGC-1α and its downstream target genes PPARα and CPT1A, which were otherwise impaired by cisplatin. In addition, the protection effects of isorhamnetin against cisplatin-induced nephrotoxicity were abolished by a PGC-1α inhibitor, SR-18292. In conclusion, our findings indicate that isorhamnetin could protect against cisplatin-induced acute kidney injury by inducing PGC-1α-dependent reprogramming of fatty acid oxidation, which highlights the clinical potential of isorhamnetin as a therapeutic approach for the management of cisplatin-induced nephrotoxicity.
[Display omitted]
•Isorhamnetin ameliorated cisplatin-induced acute kidney injury.•Isorhamnetin attenuated cisplatin-induced fatty acid oxidation dysregulation.•PGC-1α-dependent fatty acid oxidation played an essential role in the protection effect of isorhamnetin on AKI. |
doi_str_mv | 10.1016/j.freeradbiomed.2023.12.010 |
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[Display omitted]
•Isorhamnetin ameliorated cisplatin-induced acute kidney injury.•Isorhamnetin attenuated cisplatin-induced fatty acid oxidation dysregulation.•PGC-1α-dependent fatty acid oxidation played an essential role in the protection effect of isorhamnetin on AKI.</description><identifier>ISSN: 0891-5849</identifier><identifier>EISSN: 1873-4596</identifier><identifier>DOI: 10.1016/j.freeradbiomed.2023.12.010</identifier><identifier>PMID: 38101584</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acute kidney injury ; Acute Kidney Injury - chemically induced ; Acute Kidney Injury - drug therapy ; Acute Kidney Injury - metabolism ; Animals ; Antineoplastic Agents - metabolism ; Antineoplastic Agents - toxicity ; Apoptosis ; Cisplatin ; Cisplatin - toxicity ; Fatty acid oxidation ; Fatty Acids - metabolism ; Humans ; Isorhamnetin ; Kidney - metabolism ; Mice ; PGC-1α ; Quercetin - analogs & derivatives</subject><ispartof>Free radical biology & medicine, 2024-02, Vol.212, p.22-33</ispartof><rights>2023 Elsevier Inc.</rights><rights>Copyright © 2023 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c383t-3a73b38f485b477b4b16f7bac136a27f0eaf7731ad1491738dfcc47bf90f402b3</citedby><cites>FETCH-LOGICAL-c383t-3a73b38f485b477b4b16f7bac136a27f0eaf7731ad1491738dfcc47bf90f402b3</cites><orcidid>0000-0002-3676-0779</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.freeradbiomed.2023.12.010$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38101584$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Lingkun</creatorcontrib><creatorcontrib>Xie, Yaochen</creatorcontrib><creatorcontrib>Xiao, Boneng</creatorcontrib><creatorcontrib>He, Xuelin</creatorcontrib><creatorcontrib>Ying, Guanghui</creatorcontrib><creatorcontrib>Zha, Huiyan</creatorcontrib><creatorcontrib>Yang, Chen</creatorcontrib><creatorcontrib>Jin, Xuejin</creatorcontrib><creatorcontrib>Li, Guilin</creatorcontrib><creatorcontrib>Ping, Li</creatorcontrib><creatorcontrib>Wang, Jincheng</creatorcontrib><creatorcontrib>Weng, Qinjie</creatorcontrib><title>Isorhamnetin alleviates cisplatin-induced acute kidney injury via enhancing fatty acid oxidation</title><title>Free radical biology & medicine</title><addtitle>Free Radic Biol Med</addtitle><description>Cisplatin is an effective chemotherapy drug widely used in the treatment of various solid tumors. However, the clinical usage of cisplatin is limited by its nephrotoxicity. Isorhamnetin, a natural flavanol compound, displays remarkable pharmacological effects, including anti-inflammatory and anti-oxidation. In this study, we aimed to investigate the potential of isorhamnetin in alleviating acute kidney injury induced by cisplatin. In vitro study showed that isorhamnetin significantly suppressed the cytotoxic effects of cisplatin on human tubular epithelial cells. Furthermore, isorhamnetin exerted significantly inhibitory effects on cisplatin-induced apoptosis and inflammatory response. In acute kidney injury mice induced by a single intraperitoneal injection with 20 mg/kg cisplatin, oral administration of isorhamnetin two days before or 2 h after cisplatin injection effectively ameliorated renal function and renal tubule injury. Transcriptomics RNA-seq analysis of the mice kidney tissues suggested that isorhamnetin treatment may protect against cisplatin-induced nephrotoxicity via PGC-1α mediated fatty acid oxidation. Isorhamnetin achieved significant enhancements in the lipid clearance, ATP level, as well as the expression of PGC-1α and its downstream target genes PPARα and CPT1A, which were otherwise impaired by cisplatin. In addition, the protection effects of isorhamnetin against cisplatin-induced nephrotoxicity were abolished by a PGC-1α inhibitor, SR-18292. In conclusion, our findings indicate that isorhamnetin could protect against cisplatin-induced acute kidney injury by inducing PGC-1α-dependent reprogramming of fatty acid oxidation, which highlights the clinical potential of isorhamnetin as a therapeutic approach for the management of cisplatin-induced nephrotoxicity.
[Display omitted]
•Isorhamnetin ameliorated cisplatin-induced acute kidney injury.•Isorhamnetin attenuated cisplatin-induced fatty acid oxidation dysregulation.•PGC-1α-dependent fatty acid oxidation played an essential role in the protection effect of isorhamnetin on AKI.</description><subject>Acute kidney injury</subject><subject>Acute Kidney Injury - chemically induced</subject><subject>Acute Kidney Injury - drug therapy</subject><subject>Acute Kidney Injury - metabolism</subject><subject>Animals</subject><subject>Antineoplastic Agents - metabolism</subject><subject>Antineoplastic Agents - toxicity</subject><subject>Apoptosis</subject><subject>Cisplatin</subject><subject>Cisplatin - toxicity</subject><subject>Fatty acid oxidation</subject><subject>Fatty Acids - metabolism</subject><subject>Humans</subject><subject>Isorhamnetin</subject><subject>Kidney - metabolism</subject><subject>Mice</subject><subject>PGC-1α</subject><subject>Quercetin - analogs & derivatives</subject><issn>0891-5849</issn><issn>1873-4596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE1rGzEQhkVpaJykf6EIcullt_qypaWnENzEYOilOSv6GDVy11pX2jXxv6-MnUNuPQ3MPO8M8yB0S0lLCV1827QhA2TjbRy24FtGGG8pawklH9CMKskbMe8WH9GMqI42cyW6S3RVyoYQIuZcfUKXXNVNdTBDz6sy5BezTTDGhE3fwz6aEQp2sex6U5tNTH5y4LFx0wj4T_QJDjimzZQPuMIY0otJLqbfOJhxPFQuejy8Rl_TQ7pBF8H0BT6f6zV6-rH8df_YrH8-rO7v1o3jio8NN5JbroJQcyuktMLSRZDWOMoXhslAwAQpOTWeio5KrnxwTkgbOhIEYZZfo6-nvbs8_J2gjHobi4O-NwmGqWjWEdYJ1XFW0e8n1OWhlAxB73LcmnzQlOijYr3R7xTro2JNma6Ka_rL-dBkj7O37JvTCixPANR39xGyLi5CqgpjBjdqP8T_OvQPhOCWuw</recordid><startdate>20240220</startdate><enddate>20240220</enddate><creator>Wang, Lingkun</creator><creator>Xie, Yaochen</creator><creator>Xiao, Boneng</creator><creator>He, Xuelin</creator><creator>Ying, Guanghui</creator><creator>Zha, Huiyan</creator><creator>Yang, Chen</creator><creator>Jin, Xuejin</creator><creator>Li, Guilin</creator><creator>Ping, Li</creator><creator>Wang, Jincheng</creator><creator>Weng, Qinjie</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3676-0779</orcidid></search><sort><creationdate>20240220</creationdate><title>Isorhamnetin alleviates cisplatin-induced acute kidney injury via enhancing fatty acid oxidation</title><author>Wang, Lingkun ; Xie, Yaochen ; Xiao, Boneng ; He, Xuelin ; Ying, Guanghui ; Zha, Huiyan ; Yang, Chen ; Jin, Xuejin ; Li, Guilin ; Ping, Li ; Wang, Jincheng ; Weng, Qinjie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c383t-3a73b38f485b477b4b16f7bac136a27f0eaf7731ad1491738dfcc47bf90f402b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acute kidney injury</topic><topic>Acute Kidney Injury - chemically induced</topic><topic>Acute Kidney Injury - drug therapy</topic><topic>Acute Kidney Injury - metabolism</topic><topic>Animals</topic><topic>Antineoplastic Agents - metabolism</topic><topic>Antineoplastic Agents - toxicity</topic><topic>Apoptosis</topic><topic>Cisplatin</topic><topic>Cisplatin - toxicity</topic><topic>Fatty acid oxidation</topic><topic>Fatty Acids - metabolism</topic><topic>Humans</topic><topic>Isorhamnetin</topic><topic>Kidney - metabolism</topic><topic>Mice</topic><topic>PGC-1α</topic><topic>Quercetin - analogs & derivatives</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Lingkun</creatorcontrib><creatorcontrib>Xie, Yaochen</creatorcontrib><creatorcontrib>Xiao, Boneng</creatorcontrib><creatorcontrib>He, Xuelin</creatorcontrib><creatorcontrib>Ying, Guanghui</creatorcontrib><creatorcontrib>Zha, Huiyan</creatorcontrib><creatorcontrib>Yang, Chen</creatorcontrib><creatorcontrib>Jin, Xuejin</creatorcontrib><creatorcontrib>Li, Guilin</creatorcontrib><creatorcontrib>Ping, Li</creatorcontrib><creatorcontrib>Wang, Jincheng</creatorcontrib><creatorcontrib>Weng, Qinjie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Free radical biology & medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Lingkun</au><au>Xie, Yaochen</au><au>Xiao, Boneng</au><au>He, Xuelin</au><au>Ying, Guanghui</au><au>Zha, Huiyan</au><au>Yang, Chen</au><au>Jin, Xuejin</au><au>Li, Guilin</au><au>Ping, Li</au><au>Wang, Jincheng</au><au>Weng, Qinjie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Isorhamnetin alleviates cisplatin-induced acute kidney injury via enhancing fatty acid oxidation</atitle><jtitle>Free radical biology & medicine</jtitle><addtitle>Free Radic Biol Med</addtitle><date>2024-02-20</date><risdate>2024</risdate><volume>212</volume><spage>22</spage><epage>33</epage><pages>22-33</pages><issn>0891-5849</issn><eissn>1873-4596</eissn><abstract>Cisplatin is an effective chemotherapy drug widely used in the treatment of various solid tumors. However, the clinical usage of cisplatin is limited by its nephrotoxicity. Isorhamnetin, a natural flavanol compound, displays remarkable pharmacological effects, including anti-inflammatory and anti-oxidation. In this study, we aimed to investigate the potential of isorhamnetin in alleviating acute kidney injury induced by cisplatin. In vitro study showed that isorhamnetin significantly suppressed the cytotoxic effects of cisplatin on human tubular epithelial cells. Furthermore, isorhamnetin exerted significantly inhibitory effects on cisplatin-induced apoptosis and inflammatory response. In acute kidney injury mice induced by a single intraperitoneal injection with 20 mg/kg cisplatin, oral administration of isorhamnetin two days before or 2 h after cisplatin injection effectively ameliorated renal function and renal tubule injury. Transcriptomics RNA-seq analysis of the mice kidney tissues suggested that isorhamnetin treatment may protect against cisplatin-induced nephrotoxicity via PGC-1α mediated fatty acid oxidation. Isorhamnetin achieved significant enhancements in the lipid clearance, ATP level, as well as the expression of PGC-1α and its downstream target genes PPARα and CPT1A, which were otherwise impaired by cisplatin. In addition, the protection effects of isorhamnetin against cisplatin-induced nephrotoxicity were abolished by a PGC-1α inhibitor, SR-18292. In conclusion, our findings indicate that isorhamnetin could protect against cisplatin-induced acute kidney injury by inducing PGC-1α-dependent reprogramming of fatty acid oxidation, which highlights the clinical potential of isorhamnetin as a therapeutic approach for the management of cisplatin-induced nephrotoxicity.
[Display omitted]
•Isorhamnetin ameliorated cisplatin-induced acute kidney injury.•Isorhamnetin attenuated cisplatin-induced fatty acid oxidation dysregulation.•PGC-1α-dependent fatty acid oxidation played an essential role in the protection effect of isorhamnetin on AKI.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>38101584</pmid><doi>10.1016/j.freeradbiomed.2023.12.010</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-3676-0779</orcidid></addata></record> |
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subjects | Acute kidney injury Acute Kidney Injury - chemically induced Acute Kidney Injury - drug therapy Acute Kidney Injury - metabolism Animals Antineoplastic Agents - metabolism Antineoplastic Agents - toxicity Apoptosis Cisplatin Cisplatin - toxicity Fatty acid oxidation Fatty Acids - metabolism Humans Isorhamnetin Kidney - metabolism Mice PGC-1α Quercetin - analogs & derivatives |
title | Isorhamnetin alleviates cisplatin-induced acute kidney injury via enhancing fatty acid oxidation |
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