RT Journal Article
T1 Nephroprotective Effect of Cilastatin against Gentamicin-Induced Renal Injury In Vitro and In Vivo without Altering Its Bactericidal Efficiency
A1 Jado, Juan Carlos
A1 González Nicolás González, María Ángeles
A1 Humanes, Blanca
A1 Camaño, Sonia
A1 Lara, José Manuel
A1 López, Beatriz
A1 Cercenado Mansilla, Emilia
A1 García-Bordas, Julio
A1 Tejedor Jorge, Alberto
A1 Lázaro Fernández, Alberto
AB Gentamicin is a used antibiotic that causes nephrotoxicity in 10-20% of treatment periods, which limits its use considerably. Our results have shown that cilastatin may be a promising therapeutic alternative in toxin-induced acute kidney injury (AKI). Here, we investigated its potential use as a nephroprotector against gentamicin-induced AKI in vitro and in vivo. Porcine renal cells and rats were treated with gentamicin and/or cilastatin. In vivo nephrotoxicity was analyzed by measuring biochemical markers and renal morphology. Different apoptotic, oxidative and inflammatory parameters were studied at cellular and systemic levels. Megalin, mainly responsible for the entry of gentamicin into the cells, was also analyzed. Results show that cilastatin protects cells from gentamicin-induced AKI. Cilastatin decreased creatinine, BUN, kidney injury molecule-1 (KIM-1) and severe morphological changes previously increased by gentamicin in rats. The interference of cilastatin with lipid rafts cycling leads to decreased expression of megalin, and therefore gentamicin uptake and myeloid bodies, resulting in a decrease of apoptotic, oxidative and inflammatory events. Moreover, cilastatin did not prevent bacterial death by gentamicin. Cilastatin reduced gentamicin-induced AKI by preventing key steps in the amplification of the damage, which is associated to the disruption of megalin-gentamicin endocytosis. Therefore, cilastatin might represent a novel therapeutic tool in the prevention and treatment of gentamicin-induced AKI in the clinical setting.
PB MDPI
YR 2020
FD 2020-09-03
LK https://hdl.handle.net/20.500.14352/116054
UL https://hdl.handle.net/20.500.14352/116054
LA eng
NO Jado JC, Humanes B, González-Nicolás MA, Camaño S, Lara JM, Lopez B, Cercenado E, García-Bordas J, Tejedor A, Lazaro A. Nephroprotective Effect of Cilastatin against Gentamicin-Induced Renal Injury In Vitro and In Vivo without Altering Its Bactericidal Efficiency. Antioxidants (Basel). 2020 Sep 3;9(9):821.
DS Docta Complutense
RD 5 abr 2025