The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury.
Malaria-induced acute kidney injury (MAKI) is a life-threatening complication of severe malaria. Here, we investigated the potential role of the angiotensin II (Ang II)/AT1 receptor pathway in the development of MAKI. We used C57BL/6 mice infected by Plasmodium berghei ANKA (PbA-infected mice), a we...
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doaj-8d08d9414cf74d0a90931aa9917b1b642020-11-25T01:58:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01139e020383610.1371/journal.pone.0203836The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury.Leandro S SilvaDiogo B PeruchettiRodrigo P Silva-AguiarThiago P AbreuBeatriz K A Dal-CheriChristina M TakiyaMariana C SouzaMaria G HenriquesAna Acacia S PinheiroCelso Caruso-NevesMalaria-induced acute kidney injury (MAKI) is a life-threatening complication of severe malaria. Here, we investigated the potential role of the angiotensin II (Ang II)/AT1 receptor pathway in the development of MAKI. We used C57BL/6 mice infected by Plasmodium berghei ANKA (PbA-infected mice), a well-known murine model of severe malaria. The animals were treated with 20 mg/kg/day losartan, an antagonist of AT1 receptor, or captopril, an angiotensin-converting enzyme inhibitor. We observed an increase in the levels of plasma creatinine and blood urea nitrogen associated with a significant decrease in creatinine clearance, a marker of glomerular flow rate, and glomerular hypercellularity, indicating glomerular injury. PbA-infected mice also presented proteinuria and a high level of urinary γ-glutamyltransferase activity associated with an increase in collagen deposition and interstitial space, showing tubule-interstitial injury. PbA-infected mice were also found to have increased fractional excretion of sodium (FENa+) coupled with decreased cortical (Na++K+)ATPase activity. These injuries were associated with an increase in pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6, interleukin-17, and interferon gamma, in the renal cortex of PbA-infected mice. All modifications of these structural, biochemical, and functional parameters observed in PbA-infected mice were avoided with simultaneous treatment with losartan or captopril. Our data allow us to postulate that the Ang II/AT1 receptor pathway mediates an increase in renal pro-inflammatory cytokines, which in turn leads to the glomerular and tubular injuries observed in MAKI.http://europepmc.org/articles/PMC6133374?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Leandro S Silva Diogo B Peruchetti Rodrigo P Silva-Aguiar Thiago P Abreu Beatriz K A Dal-Cheri Christina M Takiya Mariana C Souza Maria G Henriques Ana Acacia S Pinheiro Celso Caruso-Neves |
spellingShingle |
Leandro S Silva Diogo B Peruchetti Rodrigo P Silva-Aguiar Thiago P Abreu Beatriz K A Dal-Cheri Christina M Takiya Mariana C Souza Maria G Henriques Ana Acacia S Pinheiro Celso Caruso-Neves The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury. PLoS ONE |
author_facet |
Leandro S Silva Diogo B Peruchetti Rodrigo P Silva-Aguiar Thiago P Abreu Beatriz K A Dal-Cheri Christina M Takiya Mariana C Souza Maria G Henriques Ana Acacia S Pinheiro Celso Caruso-Neves |
author_sort |
Leandro S Silva |
title |
The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury. |
title_short |
The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury. |
title_full |
The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury. |
title_fullStr |
The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury. |
title_full_unstemmed |
The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury. |
title_sort |
angiotensin ii/at1 receptor pathway mediates malaria-induced acute kidney injury. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2018-01-01 |
description |
Malaria-induced acute kidney injury (MAKI) is a life-threatening complication of severe malaria. Here, we investigated the potential role of the angiotensin II (Ang II)/AT1 receptor pathway in the development of MAKI. We used C57BL/6 mice infected by Plasmodium berghei ANKA (PbA-infected mice), a well-known murine model of severe malaria. The animals were treated with 20 mg/kg/day losartan, an antagonist of AT1 receptor, or captopril, an angiotensin-converting enzyme inhibitor. We observed an increase in the levels of plasma creatinine and blood urea nitrogen associated with a significant decrease in creatinine clearance, a marker of glomerular flow rate, and glomerular hypercellularity, indicating glomerular injury. PbA-infected mice also presented proteinuria and a high level of urinary γ-glutamyltransferase activity associated with an increase in collagen deposition and interstitial space, showing tubule-interstitial injury. PbA-infected mice were also found to have increased fractional excretion of sodium (FENa+) coupled with decreased cortical (Na++K+)ATPase activity. These injuries were associated with an increase in pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6, interleukin-17, and interferon gamma, in the renal cortex of PbA-infected mice. All modifications of these structural, biochemical, and functional parameters observed in PbA-infected mice were avoided with simultaneous treatment with losartan or captopril. Our data allow us to postulate that the Ang II/AT1 receptor pathway mediates an increase in renal pro-inflammatory cytokines, which in turn leads to the glomerular and tubular injuries observed in MAKI. |
url |
http://europepmc.org/articles/PMC6133374?pdf=render |
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