Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats
AbstractObjective This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats.Methods CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model...
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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.2024.2337287 |
| _version_ | 1797203450067419136 |
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| author | Zeng-lu Zheng Jun-wei Ma Yi Luo Gui-jin Liang Shi-jie Lei Ke-jin Yan Hai-bing Meng Xiu-juan Liu |
| author_facet | Zeng-lu Zheng Jun-wei Ma Yi Luo Gui-jin Liang Shi-jie Lei Ke-jin Yan Hai-bing Meng Xiu-juan Liu |
| author_sort | Zeng-lu Zheng |
| collection | DOAJ |
| description | AbstractObjective This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats.Methods CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 μg/kg, and CP + Dex 25 μg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting.Results Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1.Conclusion Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis. |
| first_indexed | 2024-04-24T08:19:31Z |
| format | Article |
| id | doaj.art-a87771378e8c446f930c022149e98a72 |
| institution | Directory Open Access Journal |
| issn | 0886-022X 1525-6049 |
| language | English |
| last_indexed | 2024-04-24T08:19:31Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj.art-a87771378e8c446f930c022149e98a722024-04-17T02:17:54ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2024.2337287Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in ratsZeng-lu Zheng0Jun-wei Ma1Yi Luo2Gui-jin Liang3Shi-jie Lei4Ke-jin Yan5Hai-bing Meng6Xiu-juan Liu7Department of Anesthesiology, The 908th Hospital of Chinese People’s Liberation Army Joint Logistic Support Force, Nanchang, ChinaDepartment of Nephrology, The 908th Hospital of Chinese People’s Liberation Army Joint Logistic Support Force, Nanchang, ChinaDepartment of Respiratory, The 908th Hospital of Chinese People’s Liberation Army Joint Logistic Support Force, Nanchang, ChinaDepartment of Anesthesiology, The 908th Hospital of Chinese People’s Liberation Army Joint Logistic Support Force, Nanchang, ChinaDepartment of Proctology, The 908th Hospital of Chinese People’s Liberation Army Joint Logistic Support Force, Nanchang, ChinaDepartment of Proctology, The 908th Hospital of Chinese People’s Liberation Army Joint Logistic Support Force, Nanchang, ChinaDepartment of Anesthesiology, The 908th Hospital of Chinese People’s Liberation Army Joint Logistic Support Force, Nanchang, ChinaDepartment of Nephrology, The 908th Hospital of Chinese People’s Liberation Army Joint Logistic Support Force, Nanchang, ChinaAbstractObjective This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats.Methods CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 μg/kg, and CP + Dex 25 μg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting.Results Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1.Conclusion Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2337287Dexmedetomidineacute kidney injurycisplatinNLRP-3/caspase-1 signaling pathwaypyroptosis |
| spellingShingle | Zeng-lu Zheng Jun-wei Ma Yi Luo Gui-jin Liang Shi-jie Lei Ke-jin Yan Hai-bing Meng Xiu-juan Liu Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats Renal Failure Dexmedetomidine acute kidney injury cisplatin NLRP-3/caspase-1 signaling pathway pyroptosis |
| title | Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats |
| title_full | Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats |
| title_fullStr | Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats |
| title_full_unstemmed | Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats |
| title_short | Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats |
| title_sort | mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats |
| topic | Dexmedetomidine acute kidney injury cisplatin NLRP-3/caspase-1 signaling pathway pyroptosis |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2337287 |
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