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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Kinin B1 receptor deficiency attenuates cisplatin-induced acute kidney injury by modulating immune cell migration

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Autor(es):
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Estrela, Gabriel R. [1, 2] ; Wasinski, Frederick [1, 2] ; Almeida, Danilo C. [2] ; Amano, Mariane T. [3] ; Castoldi, Angela [3] ; Dias, Carolina C. [1] ; Malheiros, Denise M. A. C. [4] ; Almeida, Sandro S. [1] ; Paredes-Gamero, Edgar J. [1] ; Pesquero, Joao B. [1] ; Barros, Carlos C. [5] ; Camara, Niels O. S. [3] ; Araujo, Ronaldo C. [6, 1]
Número total de Autores: 13
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Dept Biofis, BR-04023062 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Disciplina Nefrol, Dept Med, BR-04023062 Sao Paulo - Brazil
[3] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo - Brazil
[4] Univ Sao Paulo, Dept Clin Med, Sao Paulo - Brazil
[5] Univ Fed Sao Paulo, Dept Nutr, Escola Nutr, BR-04023062 Sao Paulo - Brazil
[6] Univ Fed Sao Paulo, Dept Biophys, BR-04023062 Sao Paulo - Brazil
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF MOLECULAR MEDICINE-JMM; v. 92, n. 4, p. 399-409, APR 2014.
Citações Web of Science: 6
Resumo

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. <UnorderedList Mark={''}Bullet{''}> <ItemContent> <Para>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. (AU)

Processo FAPESP: 11/03528-0 - Papel do treinamento físico na modulação da inflamação do tecido adiposo de camundongos obesos
Beneficiário:Ronaldo de Carvalho Araújo
Linha de fomento: Auxílio à Pesquisa - Regular