Synergistic effect of apoptosis and necroptosis inhibitors in cisplatin-induced nephrotoxicity

Show simple item record Tristao, Vivian Regina [UNIFESP] Pessoa, Edson A. [UNIFESP] Nakamichi, Renata [UNIFESP] Reis, Luciana A. [UNIFESP] Batista, Marcelo Costa [UNIFESP] Durao Junior, Marcelino de Souza [UNIFESP] Martins Monte, Julio Cesar [UNIFESP] 2019-01-21T10:30:16Z 2019-01-21T10:30:16Z 2016
dc.identifier.citation Apoptosis. Dordrecht, v. 21, n. 1, p. 51-59, 2016.
dc.identifier.issn 1360-8185
dc.description.abstract Necroptosis 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.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.format.extent 51-59
dc.language.iso eng
dc.publisher Springer
dc.relation.ispartof Apoptosis
dc.rights Acesso restrito
dc.subject Necroptosis en
dc.subject Necrostatin-1 en
dc.subject Cisplatin en
dc.subject Acute kidney injury en
dc.subject CytoprotectionAcute Kidney Injury en
dc.subject Gelatinase-Associated Lipocalin en
dc.subject Nonapoptotic Cell-Death en
dc.subject Ischemia/Reperfusion Injury en
dc.subject Caspase Activation en
dc.subject Urinary Biomarker en
dc.subject Renal Injury en
dc.subject Rats en
dc.subject Necrostatin-1 en
dc.subject Contributes en
dc.title Synergistic effect of apoptosis and necroptosis inhibitors in cisplatin-induced nephrotoxicity en
dc.type Artigo
dc.description.affiliation Univiversidade Federal de Sao Paulo, Sao Paulo, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Rua Pedro de Toledo,740,2 Andar, Sao Paulo, Brazil.
dc.description.sponsorshipID FAPESP: 08/09773-4
dc.description.sponsorshipID Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES).
dc.identifier.doi 10.1007/s10495-015-1190-5
dc.description.source Web of Science
dc.identifier.wos WOS:000367694200005


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