β-Hydroxybutyrate Protects Against Cisplatin-Induced Renal Damage via Regulating Ferroptosis
Cisplatin is a particularly potent antineoplastic drug. However, its usefulness is restricted due to the induction of nephrotoxicity. More recent research has indicated that β-hydroxybutyrate (β-HB) protects against acute or chronic organ damage as an efficient healing agent. Nonetheless, the therap...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2354918 |
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| author | Ruixue Tian Shuqin Tang Jingyu Zhao Yajie Hao Limei Zhao Xiutao Han Xingru Wang Lijun Zhang Rongshan Li Xiaoshuang Zhou |
| author_facet | Ruixue Tian Shuqin Tang Jingyu Zhao Yajie Hao Limei Zhao Xiutao Han Xingru Wang Lijun Zhang Rongshan Li Xiaoshuang Zhou |
| author_sort | Ruixue Tian |
| collection | DOAJ |
| description | Cisplatin is a particularly potent antineoplastic drug. However, its usefulness is restricted due to the induction of nephrotoxicity. More recent research has indicated that β-hydroxybutyrate (β-HB) protects against acute or chronic organ damage as an efficient healing agent. Nonetheless, the therapeutic mechanisms of β-HB in acute kidney damage caused by chemotherapeutic drugs remain unclear. Our study developed a model of cisplatin-induced acute kidney injury (AKI), which involved the administration of a ketogenic diet or β-HB. We analyzed blood urea nitrogen (BUN) and creatinine (Cr) levels in serum, and used western blotting and immunohistochemical staining to assess ferroptosis and the calcium/calmodulin-dependent kinase kinase 2 (Camkk2)/AMPK pathway. The mitochondrial morphology and function were examined. Additionally, we conducted in vivo and in vitro experiments using selective Camkk2 inhibitor or activator to investigate the protective mechanism of β-HB on cisplatin-induced AKI. Exogenous or endogenous β-HB effectively alleviated cisplatin-induced abnormally elevated levels of BUN and Cr and renal tubular necrosis in vivo. Additionally, β-HB reduced ferroptosis biomarkers and increased the levels of anti-ferroptosis biomarkers in the kidney. β-HB also improved mitochondrial morphology and function. Moreover, β-HB significantly attenuated cisplatin-induced cell ferroptosis and damage in vitro. Furthermore, western blotting and immunohistochemical staining indicated that β-HB may prevent kidney injury by regulating the Camkk2-AMPK pathway. The use of the Camkk2 inhibitor or activator verified the involvement of Camkk2 in the renal protection by β-HB. This study provided evidence of the protective effects of β-HB against cisplatin-induced nephrotoxicity and identified inhibited ferroptosis and Camkk2 as potential molecular mechanisms. |
| format | Article |
| id | doaj-art-43438698fc474643a9cbe4e9d4b17d7a |
| institution | Kabale University |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-43438698fc474643a9cbe4e9d4b17d7a2025-01-23T04:17:48ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2024.2354918β-Hydroxybutyrate Protects Against Cisplatin-Induced Renal Damage via Regulating FerroptosisRuixue Tian0Shuqin Tang1Jingyu Zhao2Yajie Hao3Limei Zhao4Xiutao Han5Xingru Wang6Lijun Zhang7Rongshan Li8Xiaoshuang Zhou9Department of Nephrology, Shanxi Provincial People’s Hospital; The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, ChinaDepartment of Nephrology, Shanxi Provincial People’s Hospital; The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, ChinaThe Third Clinical Medical College, Shanxi University of Chinese Medicine, Jinzhong, ChinaDepartment of Nephrology, Shanxi Provincial People’s Hospital; The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, ChinaDepartment of Nephrology, Shanxi Provincial People’s Hospital; The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, ChinaThe Third Clinical Medical College, Shanxi University of Chinese Medicine, Jinzhong, ChinaDepartment of Nephrology, Shanxi Provincial People’s Hospital; The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, ChinaDepartment of Nephrology, Shanxi Provincial People’s Hospital; The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, ChinaDepartment of Nephrology, Shanxi Provincial People’s Hospital; The Fifth Clinical Medical College of Shanxi Medical University; Shanxi Kidney Disease Institute, Taiyuan, ChinaDepartment of Nephrology, Shanxi Provincial People’s Hospital; The Fifth Clinical Medical College of Shanxi Medical University; Shanxi Kidney Disease Institute, Taiyuan, ChinaCisplatin is a particularly potent antineoplastic drug. However, its usefulness is restricted due to the induction of nephrotoxicity. More recent research has indicated that β-hydroxybutyrate (β-HB) protects against acute or chronic organ damage as an efficient healing agent. Nonetheless, the therapeutic mechanisms of β-HB in acute kidney damage caused by chemotherapeutic drugs remain unclear. Our study developed a model of cisplatin-induced acute kidney injury (AKI), which involved the administration of a ketogenic diet or β-HB. We analyzed blood urea nitrogen (BUN) and creatinine (Cr) levels in serum, and used western blotting and immunohistochemical staining to assess ferroptosis and the calcium/calmodulin-dependent kinase kinase 2 (Camkk2)/AMPK pathway. The mitochondrial morphology and function were examined. Additionally, we conducted in vivo and in vitro experiments using selective Camkk2 inhibitor or activator to investigate the protective mechanism of β-HB on cisplatin-induced AKI. Exogenous or endogenous β-HB effectively alleviated cisplatin-induced abnormally elevated levels of BUN and Cr and renal tubular necrosis in vivo. Additionally, β-HB reduced ferroptosis biomarkers and increased the levels of anti-ferroptosis biomarkers in the kidney. β-HB also improved mitochondrial morphology and function. Moreover, β-HB significantly attenuated cisplatin-induced cell ferroptosis and damage in vitro. Furthermore, western blotting and immunohistochemical staining indicated that β-HB may prevent kidney injury by regulating the Camkk2-AMPK pathway. The use of the Camkk2 inhibitor or activator verified the involvement of Camkk2 in the renal protection by β-HB. This study provided evidence of the protective effects of β-HB against cisplatin-induced nephrotoxicity and identified inhibited ferroptosis and Camkk2 as potential molecular mechanisms.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2354918β-hydroxybutyratecisplatinnephrotoxicityferroptosisCamkk2AMPK |
| spellingShingle | Ruixue Tian Shuqin Tang Jingyu Zhao Yajie Hao Limei Zhao Xiutao Han Xingru Wang Lijun Zhang Rongshan Li Xiaoshuang Zhou β-Hydroxybutyrate Protects Against Cisplatin-Induced Renal Damage via Regulating Ferroptosis Renal Failure β-hydroxybutyrate cisplatin nephrotoxicity ferroptosis Camkk2 AMPK |
| title | β-Hydroxybutyrate Protects Against Cisplatin-Induced Renal Damage via Regulating Ferroptosis |
| title_full | β-Hydroxybutyrate Protects Against Cisplatin-Induced Renal Damage via Regulating Ferroptosis |
| title_fullStr | β-Hydroxybutyrate Protects Against Cisplatin-Induced Renal Damage via Regulating Ferroptosis |
| title_full_unstemmed | β-Hydroxybutyrate Protects Against Cisplatin-Induced Renal Damage via Regulating Ferroptosis |
| title_short | β-Hydroxybutyrate Protects Against Cisplatin-Induced Renal Damage via Regulating Ferroptosis |
| title_sort | β hydroxybutyrate protects against cisplatin induced renal damage via regulating ferroptosis |
| topic | β-hydroxybutyrate cisplatin nephrotoxicity ferroptosis Camkk2 AMPK |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2354918 |
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