RT Journal Article
T1 Cilastatin protects against cisplatin-induced nephrotoxicity without compromising its anticancer efficiency in rats
A1 Humanes, Blanca
A1 Lázaro Fernández, Alberto
A1 Camano, Sonia
A1 Moreno Gordaliza, María Estefanía
A1 Lázaro, José A.
A1 Blanco Codesido, Montserrat
A1 Lara, José M.
A1 Ortiz, Alberto
A1 Gómez Gómez, María Milagros
A1 Martín Vasallo, Pablo
A1 Tejedor, Alberto
AB Cisplatin is an anticancer agent marred by nephrotoxicity; however, limiting this adverse effect may allow the use of higher doses to improve its efficacy. Cilastatin, a small molecule inhibitor of renal dehydropeptidase I, prevents proximal tubular cells from undergoing cisplatin-induced apoptosis in vitro. Here, we explored the in vivo relevance of these findings and the specificity of protection for kidney cells in cisplatin-treated rats. Cisplatin increased serum blood urea nitrogen and creatinine levels, and the fractional excretion of sodium. Cisplatin decreased the glomerular filtration rate, promoted histological renal injury and the expression of many pro-apoptotic proteins in the renal cortex, increased the Bax/Bcl2 ratio, and oxidative stress in kidney tissue and urine. All these features were decreased by cilastatin, which preserved renal function but did not modify the pharmacokinetics of cisplatin area under the curve. The cisplatin-induced death of cervical, colon, breast, and bladder-derived cancer cell lines was not prevented by cilastatin. Thus, cilastatin has the potential to prevent cisplatin nephrotoxicity without compromising its anticancer efficacy.
PB International Society of Nephrology
SN 0085-2538
YR 2012
FD 2012
LK https://hdl.handle.net/20.500.14352/42741
UL https://hdl.handle.net/20.500.14352/42741
LA eng
NO Humanes, B., Lázaro Fernández, A., Camano, S. et al. «Cilastatin Protects against Cisplatin-Induced Nephrotoxicity without Compromising Its Anticancer Efficiency in Rats». Kidney International, vol. 82, n.o 6, septiembre de 2012, pp. 652-63. DOI.org (Crossref), https://doi.org/10.1038/ki.2012.199.
NO Instituto Nacional de Salud Carlos III
NO Comisión Interministerial de Ciencia y Tecnología (España)
DS Docta Complutense
RD 6 oct 2024