Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin

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Moreno Gordaliza, Estefanía and Marazuela Lamata, María Dolores and Pastor, Óscar and Lázaro Fernández, Alberto and Gómez Gómez, María Milagros (2021) Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin. International Journal of Molecular Sciences, 22 (22). p. 12521. ISSN 1422-0067

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Official URL: https://doi.org/10.3390/ijms222212521




Abstract

Nephrotoxicity is a major complication of cisplatin-based chemotherapy, leading to acute kidney injury in ca. 30% of patients, with no preventive intervention or treatment available for clinical use. Cilastatin has proved to exert a nephroprotective effect for cisplatin therapies in in vitro and in vivo models, having recently entered clinical trials. A deeper understanding at the molecular level of cisplatin-induced renal damage and the effect of potential protective agents could be key to develop successful nephroprotective therapies and to establish new biomarkers of renal damage and nephroprotection. A targeted lipidomics approach, using LC-MS/MS, was employed for the quantification of 108 lipid species (comprising phospholipids, sphingolipids, and free and esterified cholesterol) in kidney cortex and medulla extracts from rats treated with cisplatin and/or cilastatin. Up to 56 and 63 lipid species were found to be altered in the cortex and medulla, respectively, after cisplatin treatment. Co-treatment with cilastatin attenuated many of these lipid changes, either totally or partially with respect to control levels. Multivariate analysis revealed that lipid species can be used to discriminate renal damage and nephroprotection, with cholesterol esters being the most discriminating species, along with sulfatides and phospholipids. Potential diagnostic biomarkers of cisplatin-induced renal damage and cilastatin nephroprotection were also found.


Item Type:Article
Uncontrolled Keywords:lipidomics; cisplatin; acute kidney injury; cilastatin; nephroprotection; biomarkers; cholesterol esters; sphingolipids; phospholipids; chemotherapy
Subjects:Medical sciences > Medicine > Nephrology and Urology
ID Code:71673
Deposited On:05 Apr 2022 15:16
Last Modified:06 Apr 2022 08:40

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