Publication:
Cilastatin protects against cisplatin-induced nephrotoxicity without compromising its anticancer efficiency in rats

dc.contributor.authorHumanes, Blanca
dc.contributor.authorLázaro, Alberto
dc.contributor.authorCamano, Sonia
dc.contributor.authorMoreno Gordaliza, Estefanía
dc.contributor.authorLázaro, José A.
dc.contributor.authorBlanco Codesido, Montserrat
dc.contributor.authorLara, José M.
dc.contributor.authorOrtiz, Alberto
dc.contributor.authorGómez Gómez, M.Milagros
dc.contributor.authorMartín Vasallo, Pablo
dc.contributor.authorTejedor, Alberto
dc.date.accessioned2023-06-20T00:33:59Z
dc.date.available2023-06-20T00:33:59Z
dc.date.issued2012
dc.description.abstractCisplatin 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.
dc.description.departmentDepto. de Química Analítica
dc.description.facultyFac. de Ciencias Químicas
dc.description.refereedTRUE
dc.description.sponsorshipInstituto Nacional de Salud Carlos III
dc.description.sponsorshipCICYT
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/44669
dc.identifier.doi10.1038/ki.2012.199
dc.identifier.issn1523-1755 (On line), 0085-2538 (Print)
dc.identifier.officialurlhttp://www.kidney-international.org/article/S0085-2538(15)55616-0/fulltext
dc.identifier.urihttps://hdl.handle.net/20.500.14352/42741
dc.issue.number6
dc.journal.titleKidney International
dc.language.isoeng
dc.page.final663
dc.page.initial652
dc.publisherInternational Society of Nephrology
dc.relation.projectID(FIS-PI08/1481)
dc.relation.projectIDCTQ2008-04873
dc.rights.accessRightsrestricted access
dc.subject.cdu543
dc.subject.keywordapoptosis
dc.subject.keywordcilastatin
dc.subject.keywordcisplatin
dc.subject.keywordnephroprotection
dc.subject.keywordnephrotoxicity
dc.subject.ucmQuímica analítica (Química)
dc.subject.unesco2301 Química Analítica
dc.titleCilastatin protects against cisplatin-induced nephrotoxicity without compromising its anticancer efficiency in rats
dc.typejournal article
dc.volume.number82
dspace.entity.typePublication
Files
Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
PDF-definitivo-6-2012.pdf
Size:
790.74 KB
Format:
Adobe Portable Document Format
Collections