Tetrahydrocurcumin protects against sepsis-induced acute kidney injury via the SIRT1 pathway
Sepsis-induced acute kidney injury (AKI) continues to be associated with poor outcomes in critical care patients. Previous research has revealed that tetrahydrocurcumin (THC) exerts renoprotective effects in multiple nephritic disorders by modulating inflammation and oxidative stress. However, the e...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Renal Failure |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/0886022X.2021.1942915 |
| _version_ | 1798031725875429376 |
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| author | Lu Li Xiaoxi Liu Shasha Li Qingyan Wang Hongru Wang Menglu Xu Yanxin An |
| author_facet | Lu Li Xiaoxi Liu Shasha Li Qingyan Wang Hongru Wang Menglu Xu Yanxin An |
| author_sort | Lu Li |
| collection | DOAJ |
| description | Sepsis-induced acute kidney injury (AKI) continues to be associated with poor outcomes in critical care patients. Previous research has revealed that tetrahydrocurcumin (THC) exerts renoprotective effects in multiple nephritic disorders by modulating inflammation and oxidative stress. However, the effects of THC on sepsis-induced AKI and the underlying mechanisms remain unclear. In this study, a mouse model of sepsis-induced AKI, generated by cecal ligation and puncture operation, was used to investigate the protective effects of THC and the role of SIRT1. Histological manifestation and TUNEL analysis were observed to determine the severity of kidney damage. Levels of BUN, SCr, KIM-1, and UAlb/Cr were calculated to assess the renal function. Expressions of IL-1β, IL-6, and TNF-α were measured to evaluate the inflammatory response. MDA content, SOD, GSH, CAT, and GPx activities and DHE staining were analyzed to estimate the degree of oxidative stress. Protein expressions of SIRT1, Ac-p65, and Ac-foxo1 were detected to explore the underlying mechanisms. We observed that THC not only increased the survival rate, improved the kidney function and ameliorated the renal histological damage of septic mice, but also inhibited inflammatory response, prohibited oxidative stress, and prevented cell apoptosis in renal tissues in septic mice. Mechanistically, THC remarkably increased the expression of SIRT1, accompanied by decreased expressions of downstream molecules Ac-p65 and Ac-foxo1. Meanwhile, the beneficial effects of THC were clearly abolished by the SIRT1-specific inhibitor EX527. These results delineate that THC prevents sepsis-induced AKI by suppressing inflammation and oxidative stress through activating the SIRT1 signaling. Abbreviation: Ac-p65: acetylated p65; Ac-foxo 1: acetylated forkhead box O1; AKI: acute kidney injury; BUN: blood urea nitrogen; CAT: catalase; DHE: dihydroethidium; GPx: glutathione peroxidase; GSH: reduced glutathione; IL-1β: Interleukin-1 beta; IL-6: Interleukin-6; KIM-1: kidney injury molecule 1; MDA: malondialdehyde; SCr: serum creatinine; SIRT1: silent information regulator 1; SOD: superoxide dismutase; THC: tetrahydrocurcumin; TNF-α: tumor necrosis factor-alpha; TUNEL: TdT-mediated dUTP Nick-End Labeling; UAlb/Cr: urine micro albumin/creatinine. |
| first_indexed | 2024-04-11T20:02:12Z |
| format | Article |
| id | doaj.art-2d0185cbe76a4eff84fe2569a173d87f |
| institution | Directory Open Access Journal |
| issn | 0886-022X 1525-6049 |
| language | English |
| last_indexed | 2024-04-11T20:02:12Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj.art-2d0185cbe76a4eff84fe2569a173d87f2022-12-22T04:05:32ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492021-01-014311028104010.1080/0886022X.2021.19429151942915Tetrahydrocurcumin protects against sepsis-induced acute kidney injury via the SIRT1 pathwayLu Li0Xiaoxi Liu1Shasha Li2Qingyan Wang3Hongru Wang4Menglu Xu5Yanxin An6Department of Nephrology, The First Affiliated Hospital, Xi’an Medical UniversityDepartment of Nephrology, The First Affiliated Hospital, Xi’an Medical UniversityDepartment of Nephrology, The First Affiliated Hospital, Xi’an Medical UniversityDepartment of Nephrology, The First Affiliated Hospital, Xi’an Medical UniversityDepartment of Nephrology, The First Affiliated Hospital, Xi’an Medical UniversityDepartment of Nephrology, The First Affiliated Hospital, Xi’an Medical UniversityDepartment of General Surgery, The First Affiliated Hospital, Xi’an Medical UniversitySepsis-induced acute kidney injury (AKI) continues to be associated with poor outcomes in critical care patients. Previous research has revealed that tetrahydrocurcumin (THC) exerts renoprotective effects in multiple nephritic disorders by modulating inflammation and oxidative stress. However, the effects of THC on sepsis-induced AKI and the underlying mechanisms remain unclear. In this study, a mouse model of sepsis-induced AKI, generated by cecal ligation and puncture operation, was used to investigate the protective effects of THC and the role of SIRT1. Histological manifestation and TUNEL analysis were observed to determine the severity of kidney damage. Levels of BUN, SCr, KIM-1, and UAlb/Cr were calculated to assess the renal function. Expressions of IL-1β, IL-6, and TNF-α were measured to evaluate the inflammatory response. MDA content, SOD, GSH, CAT, and GPx activities and DHE staining were analyzed to estimate the degree of oxidative stress. Protein expressions of SIRT1, Ac-p65, and Ac-foxo1 were detected to explore the underlying mechanisms. We observed that THC not only increased the survival rate, improved the kidney function and ameliorated the renal histological damage of septic mice, but also inhibited inflammatory response, prohibited oxidative stress, and prevented cell apoptosis in renal tissues in septic mice. Mechanistically, THC remarkably increased the expression of SIRT1, accompanied by decreased expressions of downstream molecules Ac-p65 and Ac-foxo1. Meanwhile, the beneficial effects of THC were clearly abolished by the SIRT1-specific inhibitor EX527. These results delineate that THC prevents sepsis-induced AKI by suppressing inflammation and oxidative stress through activating the SIRT1 signaling. Abbreviation: Ac-p65: acetylated p65; Ac-foxo 1: acetylated forkhead box O1; AKI: acute kidney injury; BUN: blood urea nitrogen; CAT: catalase; DHE: dihydroethidium; GPx: glutathione peroxidase; GSH: reduced glutathione; IL-1β: Interleukin-1 beta; IL-6: Interleukin-6; KIM-1: kidney injury molecule 1; MDA: malondialdehyde; SCr: serum creatinine; SIRT1: silent information regulator 1; SOD: superoxide dismutase; THC: tetrahydrocurcumin; TNF-α: tumor necrosis factor-alpha; TUNEL: TdT-mediated dUTP Nick-End Labeling; UAlb/Cr: urine micro albumin/creatinine.http://dx.doi.org/10.1080/0886022X.2021.1942915sepsisacute kidney injurytetrahydrocurcuminsirt1inflammationoxidative stress |
| spellingShingle | Lu Li Xiaoxi Liu Shasha Li Qingyan Wang Hongru Wang Menglu Xu Yanxin An Tetrahydrocurcumin protects against sepsis-induced acute kidney injury via the SIRT1 pathway Renal Failure sepsis acute kidney injury tetrahydrocurcumin sirt1 inflammation oxidative stress |
| title | Tetrahydrocurcumin protects against sepsis-induced acute kidney injury via the SIRT1 pathway |
| title_full | Tetrahydrocurcumin protects against sepsis-induced acute kidney injury via the SIRT1 pathway |
| title_fullStr | Tetrahydrocurcumin protects against sepsis-induced acute kidney injury via the SIRT1 pathway |
| title_full_unstemmed | Tetrahydrocurcumin protects against sepsis-induced acute kidney injury via the SIRT1 pathway |
| title_short | Tetrahydrocurcumin protects against sepsis-induced acute kidney injury via the SIRT1 pathway |
| title_sort | tetrahydrocurcumin protects against sepsis induced acute kidney injury via the sirt1 pathway |
| topic | sepsis acute kidney injury tetrahydrocurcumin sirt1 inflammation oxidative stress |
| url | http://dx.doi.org/10.1080/0886022X.2021.1942915 |
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