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Title: Kinin B1 receptor deficiency attenuates cisplatin-induced acute kidney injury by modulating immune cell migration
Authors: Estrela, Gabriel R. [UNIFESP]
Wasinski, Frederick [UNIFESP]
Almeida, Danilo C. [UNIFESP]
Amano, Mariane T.
Castoldi, Angela
Dias, Carolina C. [UNIFESP]
Malheiros, Denise M. A. C.
Almeida, Sandro S. [UNIFESP]
Paredes-Gamero, Edgar J. [UNIFESP]
Pesquero, Joao B. [UNIFESP]
Barros, Carlos C. [UNIFESP]
Camara, Niels O. S.
Araujo, Ronaldo C. [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Keywords: Kinins
Acute kidney
Issue Date: 1-Apr-2014
Publisher: Springer
Citation: Journal of Molecular Medicine-jmm. New York: Springer, v. 92, n. 4, p. 399-409, 2014.
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.<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.
ISSN: 0946-2716
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