RT Journal Article
T1 Untargeted metabolomics analysis of serum and urine unveils the protective effect of cilastatin on altered metabolic pathways during cisplatin-induced acute kidney injury
A1 Moreno Gordaliza, María Estefanía
A1 González Nicolás González, María Ángeles
A1 Lázaro Fernández, Alberto
A1 Barbas, C.
A1 Gómez Gómez, María Milagros
A1 López-Gonzálvez, A.
AB Acute kidney injury (AKI) is one of the most serious complications of cisplatin anticancer therapies. Cilastatin is a highly promising nephroprotective agent to eventually enter clinical use, but its biochemical mechanism is still not fully understood. We have employed an untargeted metabolomics approach based on capillary electrophoresis mass spectrometry (CE-MS) analysis of serum and urine from an in vivo rat model, to explore the metabolic pathways involved in cisplatin-induced AKI and cilastatin nephroprotection. A total of 155 and 76 identified metabolites were found to be significantly altered during cisplatin treatment in urine and serum, respectively. Most of these altered metabolites were either partially or totally recovered by cilastatin and cisplatin cotreatment. The main metabolic pathways disturbed by cisplatin during AKI involved diverse amino acids metabolism and biosynthesis, tricarboxylic acids (TCA) cycle, nicotinate and nicotinamide metabolism, among others. Cilastatin was proved to protect diverse cisplatin-altered pathways involving metabolites related to immunomodulation, inflammation, oxidative stress and amino acid metabolism in proximal tubules. However, cisplatin-altered mitochondrial metabolism (especially, the energy-producing TCA cycle) remained largely unprotected by cilastatin, suggesting an unresolved mitochondrial direct damage. Multivariate analysis allowed effective discrimination of cisplatin-induced AKI and cilastatin renoprotection based on metabolic features. A number of potential serum and urine biomarkers could also be foreseen for cisplatin-induced AKI detection and cilastatin nephroprotection.
PB Elsevier
YR 2024
FD 2024-07-15
LK https://hdl.handle.net/20.500.14352/107086
UL https://hdl.handle.net/20.500.14352/107086
LA eng
NO Estefanía Moreno-Gordaliza, M. Ángeles González-Nicolás, Alberto Lázaro, Coral Barbas, M. Milagros Gómez-Gómez, Ángeles López-Gonzálvez, Untargeted metabolomics analysis of serum and urine unveils the protective effect of cilastatin on altered metabolic pathways during cisplatin-induced acute kidney injury, Biochemical Pharmacology, Volume 227, 2024, 116435, ISSN 0006-2952, https://doi.org/10.1016/j.bcp.2024.116435. (https://www.sciencedirect.com/science/article/pii/S0006295224004180)
DS Docta Complutense
RD 8 abr 2025