{"title":"Tolvaptan Improves Contrast-Induced Acute Kidney Injury.","authors":"Chunyang Xu, Xu Huang, Gaoliang Yan, Dong Wang, Meijuan Hu, Chengchun Tang","doi":"10.1155/2022/7435292","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Contrast-induced acute kidney injury (CI-AKI) is a serious side effect of contrast media use. The purpose of this study was to investigate the role and mechanism of tolvaptan (TOL) in CI-AKI.</p><p><strong>Methods: </strong>24 Wistar male rats were randomly divided into 4 groups (<i>n</i> = 6). And a rat model of CI-AKI was established. Then, the blood and urine of rats in each group were collected to detect relevant parameters. HE staining was utilized for the observation of the pathological changes of rat kidney tissues, TUNEL assay for the detection of tubular cell apoptosis, biochemical detection for the confirmation of oxidative stress level in kidney tissues, and western blot for the test of the expression of apoptotic proteins and the Nrf2 signaling pathway-related proteins in kidney tissues.</p><p><strong>Results: </strong>TOL could significantly reduce the serum level of urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decrease serum Cys-C and urine KIM-1 in CI-AKI rats. The result above meant that TOL could improve kidney injury and reduce tubular cell apoptosis in CI-AKI rats. In addition, TOL contributed to a reduction of oxidative stress level by downregulating myeloperoxidase level and increasing the activities of superoxide dismutase and glutathione peroxidase in the kidney tissue of CI-AKI rats. After the pretreatment of TOL, the expression of proapoptotic proteins cleaved-caspase 3 and BAX, as well as mitochondrial fusion proteins DRP1 and MFN2 was downregulated, while the expression of Bcl-2 and PINK1 was upregulated in the kidney tissue of CI-AKI rats. Further, TOL could activate the Nrf2 signaling pathway, and the Nrf2 inhibitor ML385 reversed the effect of TOL on CI-AKI.</p><p><strong>Conclusion: </strong>TOL can improve CI-AKI by activating the Nrf2/HO-1 signaling pathway, inhibiting oxidative stress response, and reducing tubular cell apoptosis.</p>","PeriodicalId":17330,"journal":{"name":"Journal of the Renin-Angiotensin-Aldosterone System","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2022-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818441/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Renin-Angiotensin-Aldosterone System","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2022/7435292","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: Contrast-induced acute kidney injury (CI-AKI) is a serious side effect of contrast media use. The purpose of this study was to investigate the role and mechanism of tolvaptan (TOL) in CI-AKI.
Methods: 24 Wistar male rats were randomly divided into 4 groups (n = 6). And a rat model of CI-AKI was established. Then, the blood and urine of rats in each group were collected to detect relevant parameters. HE staining was utilized for the observation of the pathological changes of rat kidney tissues, TUNEL assay for the detection of tubular cell apoptosis, biochemical detection for the confirmation of oxidative stress level in kidney tissues, and western blot for the test of the expression of apoptotic proteins and the Nrf2 signaling pathway-related proteins in kidney tissues.
Results: TOL could significantly reduce the serum level of urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decrease serum Cys-C and urine KIM-1 in CI-AKI rats. The result above meant that TOL could improve kidney injury and reduce tubular cell apoptosis in CI-AKI rats. In addition, TOL contributed to a reduction of oxidative stress level by downregulating myeloperoxidase level and increasing the activities of superoxide dismutase and glutathione peroxidase in the kidney tissue of CI-AKI rats. After the pretreatment of TOL, the expression of proapoptotic proteins cleaved-caspase 3 and BAX, as well as mitochondrial fusion proteins DRP1 and MFN2 was downregulated, while the expression of Bcl-2 and PINK1 was upregulated in the kidney tissue of CI-AKI rats. Further, TOL could activate the Nrf2 signaling pathway, and the Nrf2 inhibitor ML385 reversed the effect of TOL on CI-AKI.
Conclusion: TOL can improve CI-AKI by activating the Nrf2/HO-1 signaling pathway, inhibiting oxidative stress response, and reducing tubular cell apoptosis.
期刊介绍：
JRAAS is a peer-reviewed, open access journal, serving as a resource for biomedical professionals, primarily with an active interest in the renin-angiotensin-aldosterone system in humans and other mammals. It publishes original research and reviews on the normal and abnormal function of this system and its pharmacology and therapeutics, mostly in a cardiovascular context but including research in all areas where this system is present, including the brain, lungs and gastro-intestinal tract.
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