title: Kinin B1 receptor deficiency attenuates cisplatin-induced acute kidney injury by modulating immune cell migration.
abstract: Cisplatin is a chemotherapeutic agent that causes severe renal dysfunction. The kinin B1 receptor has been associated with the migration of immune cells to injured tissue as well as with renal inflammation. To examine the role of the kinin B1 receptor in cisplatin-induced acute kidney injury, we used kinin B1 receptor knockout mice and treatment with a receptor antagonist before and after cisplatin administration. Cisplatin injection caused exacerbation of renal macrophage and neutrophil migration, higher levels of serum creatinine and blood urea, upregulation of B1 receptor mRNA and an increase in pro-inflammatory cytokines expression. B1 receptor knockout mice exhibited a reduction in serum creatinine and blood urea levels, diminished apoptosis, and decreased cisplatin-induced upregulation of inflammatory components. Moreover, treatment with the B1 receptor antagonist prior to cisplatin administration normalized serum creatinine, blood urea levels, protected from acute tubular necrosis, apoptosis-related genes, and prevented upregulation of pro-inflammatory cytokines. Thus, we propose that kinins have an important role in cisplatin-induced acute kidney injury by impairing immune cells migration to renal tissue during cisplatin nephrotoxicity.
  
  
  CONCLUSIONS
  Kinin B1 receptor is upregulated after cisplatin exposure. Kinin B1 receptor deficiency diminishes the nephrotoxicity caused by cisplatin. Kinin B1 receptor deficiency ameliorates the inflammatory response. Kinin B1 receptor deficiency diminishes apoptosis caused by cisplatin. Kinin B1 receptor antagonism ameliorates renal function after cisplatin injection.
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Gabriel R
authors.initials: GR
authors.lastname: Estrela
authors.forename: Frederick
authors.initials: F
authors.lastname: Wasinski
authors.forename: Danilo C
authors.initials: DC
authors.lastname: Almeida
authors.forename: Mariane T
authors.initials: MT
authors.lastname: Amano
authors.forename: Angela
authors.initials: A
authors.lastname: Castoldi
authors.forename: Carolina C
authors.initials: CC
authors.lastname: Dias
authors.forename: Denise M A C
authors.initials: DM
authors.lastname: Malheiros
authors.forename: Sandro S
authors.initials: SS
authors.lastname: Almeida
authors.forename: Edgar J
authors.initials: EJ
authors.lastname: Paredes-Gamero
authors.forename: João B
authors.initials: JB
authors.lastname: Pesquero
authors.forename: Carlos C
authors.initials: CC
authors.lastname: Barros
authors.forename: Niels O S
authors.initials: NO
authors.lastname: Câmara
authors.forename: Ronaldo C
authors.initials: RC
authors.lastname: Araújo
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D017209:Apoptosis; D001806:Blood Urea Nitrogen; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists / Q000494:pharmacology; D002465:Cell Movement; D049109:Cell Proliferation; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043783:Receptor, Bradykinin B1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D065169:Bradykinin B1 Receptor Antagonists; D016207:Cytokines; C120984:R 715; D043783:Receptor, Bradykinin B1; D003404:Creatinine; D002945:Cisplatin; D001920:Bradykinin