title: Nec-1 protects against nonapoptotic cell death in cisplatin-induced kidney injury.
abstract: OBJECTIVE
  Necrostatin-1 (Nec-1) inhibits necroptosis, a nonapoptotic cell death pathway. Acute kidney injury (AKI) is a clinical problem of high incidence and mortality. It involves several mechanisms of cell death. We aim to evaluate the effect of Nec-1 in the toxic kidney injury model by cisplatin.
  
  
  METHODS
  We analyzed the effect of Nec-1 in AKI by cisplatin in human proximal tubule cells by flow cytometry.
  
  
  RESULTS
  Our results show that Nec-1 has no effect on apoptosis in renal tubular epithelial cells (Nec-1 + Cis group 13.4 ± 1.7% vs. Cis group 14.6 ± 1.4%) (p > 0.05). But, in conditions in which apoptosis was blocked by benzyloxy-carbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-fmk) the use of Nec-1 completely reversed cell viability (Nec-1 + Cis + z-VAD group 72.9 ± 6.3% vs. Cis group 35.5 ± 2.2%) (p < 0.05) suggesting that Nec-1 has effect on nonapoptotic cell death (necroptosis).
  
  
  CONCLUSIONS
  Our findings suggest that the combined use of apoptosis and necroptosis inhibitors can provide additional cytoprotection in AKI. Furthermore, this is the first study to demonstrate that Nec-1 inhibits tubular kidney cell death and restores cell viability via a nonapoptotic mechanism.
authors.affiliation: Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Vivian Regina
authors.initials: VR
authors.lastname: Tristão
authors.forename: Paula Fernanda
authors.initials: PF
authors.lastname: Gonçalves
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Dalboni
authors.forename: Marcelo Costa
authors.initials: MC
authors.lastname: Batista
authors.forename: Marcelino de Souza
authors.initials: Mde S
authors.lastname: Durão
authors.forename: Júlio Cesar Martins
authors.initials: JC
authors.lastname: Monte
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control; D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008856:Microscopy, Fluorescence
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007211:Indoles; C507699:necrostatin-1; D002945:Cisplatin