Aliskiren reduces the peritoneal fibrosis <i>in vivo</i> after chronic peritoneal dialysis.

<p>The groups of animals were the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036268#pone-0036268-g003" target="_blank">Fig. 3</a>. At the end of the 4 week-dialysis period, peritoneal mesothelial cells (PMCs) were isolated and the fibronectin (a) and collagen III (b) mRNA levels were determined in PMCs and normalized to the β-actin mRNA levels. The dialysis fluid used and the treatment for each group is indicated in the graph. Each histogram represents mean ± s.e.m. of 6 animals. *p<0.05 as compared to the vehicle group. ^#p<0.05 for the aliskiren-treated groups as compared to the same PDF in absence of aliskiren. ^$p<0.05 as compared to 10 mg/L aliskiren groups. c) Masson's trichrome staining of parietal peritoneum. <u>Top panel</u>. Histological sections from the vehicle, 1.5$$</sup>p<0.01 as compared to 10 mg/L aliskiren groups.</p

Aliskiren decreases fibrosis markers and inhibits changes in apoptosis markers induced by peritoneal dialysis fluids (PDFs) in rat peritoneal mesothelial cells (PMCs).

<p>Cells were treated for 24 h with a 1.5%-glucose PDF diluted 1∶1 in culture medium in the absence (V) or the presence of aliskiren, and the levels of mRNA for p53 (a), Bax (b), Bcl-2 (c), collagen III (d) and fibronectin (e) were determined by real-time RT-PCR. Data represent mean ± s.e.m. of 4 experiments. *p<0.05 as compared to untreated control cells (C). ^#p<0.01 as compared to cells treated with vehicle and PDF (V).</p

<i>In vivo</i> effect of aliskiren on p53, Bax and Bcl-2 mRNA levels in the peritoneum after daily peritoneal dialysis for 4 weeks.

<p>Twelve groups of 6 rats each one were dialyzed daily as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036268#s4" target="_blank">Methods</a> for 4 weeks in the absence (black histograms) and in the presence of aliskiren (10 and 100 mg/L). At the end of this period, peritoneal mesothelial cells (PMCs) were isolated and the mRNA levels for p53 (a), Bax (b), and Bcl-2 (c) quantified and normalized to the the β-actin mRNA levels. The dialysis fluid and the treatment for each group is indicated in the graph. Each histogram represents mean ± s.e.m. of 6 animals. *p<0.05 as compared to the vehicle group. ^#p<0.05 for the aliskiren-treated groups as compared to the same PDF in absence of aliskiren. ^$p<0.05 as compared to 10 mg/L aliskiren groups.</p

Aliskiren decreases toxicity induced by peritoneal dialysis fluids (PDFs) in rat peritoneal mesothelial cells (PMCs).

<p>a) Effect of aliskiren on PDF-mediated reactive oxygen species (ROS) production in PMCs. Cells were treated for 8 h with a 1.5%-glucose PDF diluted 1∶1 in culture medium in the absence (V) or the presence of aliskiren. ROS production was measured using dichlorodihydrofluorescein (DCF) as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036268#s4" target="_blank">Methods</a>. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036268#s2" target="_blank">Results</a> represent mean ± s.e.m. of 4 experiments. *p<0.05 as compared to untreated control cells (C). ^#p<0.05 as compared to cells treated with vehicle and high-glucose PDF (V). b) Effect of aliskiren on phospho-p38 (p-p38) mitogen-activated protein kinase (MAPK)/p38 MAPK ratio in rat PMCs exposed to a high-glucose PDF for 24 h. PMCs were treated as above, in the absence (V) or presence of aliskiren and then both p-p38 MAPK and p38 MAPK protein levels were determined by western blot. The histograms represent a densitometric analysis of the p-p38 MAPK/p38 MAPK ratio. Data represent mean ± s.e.m. of 4 experiments.*p<0.05 as compared to C. #p<0.01 as compared to V. c) Effect of aliskiren on caspase-3 activity in rat PMCs exposed to a high-glucose PDF for 18 h. PMCs were treated as above, in the absence (V) or presence of aliskiren and then caspase-3 activity was determined (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036268#s4" target="_blank">Methods</a>). Data represent mean ± s.e.m. of 4 experiments. *p<0.05 as compared to C. ^#p<0.05 as compared to V.</p

Aliskiren decreases the levels of inflammatory markers <i>in vivo</i> in both serum and dialysate after chronic peritoneal dialysis.

<p>The groups of animals were the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036268#pone-0036268-g003" target="_blank">Fig. 3</a>. A Peritoneal Equilibration Test (PET) was performed for 2 h at the end of the 4 weeks of dialysis. The levels of amyloid-P protein (a, b) and C-reactive protein (c, d) were determined in both serum (a, c) and dialysate (b, d) collected after 2 h dwell time. The dialysis fluid used and the treatment for each group is indicated in the graph. Each histogram represents mean ± s.e.m. of 6 animals. *p<0.05 as compared to the vehicle group. **p<0.01 as compared to the vehicle group. ^#p<0.05 for the aliskiren-treated groups as compared to the same PDF in absence of aliskiren. ^$p<0.05 as compared to 10 mg/L aliskiren groups.</p