{"title":"Screening for Early Biomarkers of Cisplatin-Induced Acute Kidney Injury in Rats Through Serum Metabolomics Technology.","authors":"Jinru Yang, Mingkang Zhang, Fenglin Ran, Xueyan Gou, Yanrong Ma, Xinan Wu","doi":"10.29271/jcpsp.2024.08.936","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To systematically identify early biomarkers of cisplatin-induced acute kidney injury (AKI) in rats.</p><p><strong>Study design: </strong>An experimental study. Place and Duration of the Study: Experimental Animal Laboratory of Lanzhou University, Gansu, China, and the Department of Pharmacy, The First Hospital of Lanzhou University, Gansu, China, from July 2022 to October 2023.</p><p><strong>Methodology: </strong>In this study, an AKI model was established by continuously injecting cisplatin into rats at a dose of 1 mg/kg once a day for control group and for 2, 3, 4, and 5 days to other four groups, respectively. Subsequently, rat plasma samples were collected for metabolomics analysis to identify early differentiated metabolites in the plasma prior to creatinine elevation. Furthermore, accurate HPLC-MS/MS methods were developed to validate the biomarker variation in other AKI models.</p><p><strong>Results: </strong>The occurrence of time-dependent renal cortical injury and significant alterations of creatinine (Cr) concentration were observed on day-4 and 5, which demonstrated successful model construction. Sixty-six compounds changed on Day-2 while 61 compounds changed on Day-3. Eleven compounds with variable importance in projection (VIP) >1.5 and false discover rate (FDR) <0.2 were selected and identified by HPLC-MS/MS. Among these, N-acetylglutamine and citramalic acid changed earlier than serum creatinine (sCr) in the AKI model.</p><p><strong>Conclusion: </strong>N-acetylglutamine and citramalic acid may serve as early biomarker of cisplatin-induced AKI.</p><p><strong>Key words: </strong>Acute kidney injury, Biomarker, Cisplatin, Metabolomics, LC-MS/MS, Rats.</p>","PeriodicalId":94116,"journal":{"name":"Journal of the College of Physicians and Surgeons--Pakistan : JCPSP","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the College of Physicians and Surgeons--Pakistan : JCPSP","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.29271/jcpsp.2024.08.936","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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Abstract
Objective: To systematically identify early biomarkers of cisplatin-induced acute kidney injury (AKI) in rats.
Study design: An experimental study. Place and Duration of the Study: Experimental Animal Laboratory of Lanzhou University, Gansu, China, and the Department of Pharmacy, The First Hospital of Lanzhou University, Gansu, China, from July 2022 to October 2023.
Methodology: In this study, an AKI model was established by continuously injecting cisplatin into rats at a dose of 1 mg/kg once a day for control group and for 2, 3, 4, and 5 days to other four groups, respectively. Subsequently, rat plasma samples were collected for metabolomics analysis to identify early differentiated metabolites in the plasma prior to creatinine elevation. Furthermore, accurate HPLC-MS/MS methods were developed to validate the biomarker variation in other AKI models.
Results: The occurrence of time-dependent renal cortical injury and significant alterations of creatinine (Cr) concentration were observed on day-4 and 5, which demonstrated successful model construction. Sixty-six compounds changed on Day-2 while 61 compounds changed on Day-3. Eleven compounds with variable importance in projection (VIP) >1.5 and false discover rate (FDR) <0.2 were selected and identified by HPLC-MS/MS. Among these, N-acetylglutamine and citramalic acid changed earlier than serum creatinine (sCr) in the AKI model.
Conclusion: N-acetylglutamine and citramalic acid may serve as early biomarker of cisplatin-induced AKI.
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