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dc.contributor.authorTristao, Vivian Regina [UNIFESP]
dc.contributor.authorPessoa, Edson A. [UNIFESP]
dc.contributor.authorNakamichi, Renata [UNIFESP]
dc.contributor.authorReis, Luciana A. [UNIFESP]
dc.contributor.authorBatista, Marcelo Costa [UNIFESP]
dc.contributor.authorDurao Junior, Marcelino de Souza [UNIFESP]
dc.contributor.authorMartins Monte, Julio Cesar [UNIFESP]
dc.identifier.citationApoptosis. Dordrecht, v. 21, n. 1, p. 51-59, 2016.
dc.description.abstractNecroptosis is a nonapoptotic cell death pathway. We aim to study the effect of necrostatin-1 (a specific necroptosis inhibitor) in cisplatin-induced injury. We analyzed the effect of the combined use of inhibitors of apoptosis (z-vad) and necroptosis (necrostatin-1) in acute kidney injury by cisplatin in human proximal tubule cells. Our results showed moderate effectiveness in cytoprotection after treatment with z-vad. But the concomitant use of inhibitors (z-vad and necrostatin-1) presented synergistic and additive protection. The present study analyzed the caspase-3 activity and we observed a significant decrease in the group treated with z-vad and cisplatin. However we did not observe changes in the group treated with both inhibitors (z-vad and necrostatin-1) and cisplatin. Thus, demonstrating that necroptosis is a caspase-independent mechanism. We also analyzed the effect of necrostatin-1 in vivo model. C57BL/6 mice were treated with cisplatin and/or inhibitors. The concomitant use of inhibitors (z-vad and necrostatin-1) recovered renal function and decreased levels of urinary Ngal. Additionally, we analyzed the expression of RIP-1, a specific marker for necroptosis. In animals treated with cisplatin and z-VAD levels of RIP-1 were higher. This result reinforces that necroptosis occurs only in conditions where apoptosis was blocked. However, the use of both inhibitors (z-vad and necrostatin-1) provided additional protection. In conclusion, our study has a significant potential to show in vitro and in vivo protection obtained by necrostatin-1. Therefore, our results suggest that necroptosis may be an important mechanism of cell death after kidney injury.en
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.rightsAcesso restrito
dc.subjectAcute kidney injuryen
dc.subjectCytoprotectionAcute Kidney Injuryen
dc.subjectGelatinase-Associated Lipocalinen
dc.subjectNonapoptotic Cell-Deathen
dc.subjectIschemia/Reperfusion Injuryen
dc.subjectCaspase Activationen
dc.subjectUrinary Biomarkeren
dc.subjectRenal Injuryen
dc.titleSynergistic effect of apoptosis and necroptosis inhibitors in cisplatin-induced nephrotoxicityen
dc.description.affiliationUniviversidade Federal de Sao Paulo, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Rua Pedro de Toledo,740,2 Andar, Sao Paulo, Brazil.
dc.description.sponsorshipIDFAPESP: 08/09773-4
dc.description.sponsorshipIDCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES).
dc.description.sourceWeb of Science

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