Fig. 3
From: Aldose reductase mediates endothelial cell dysfunction induced by high uric acid concentrations
The AR inhibitor alleviated oxidative stress and impaired HUVECs by inhibiting NADPH oxidase activity. a and b Nox4 production was up-regulated in endothelial cells cultured in the presence of 600 μM UA for 24 h (*P < 0.05 vs. control, n = 6), but down-regulated in Epalrestat + HUA cells pretreated with epalrestat (0.1 μM) for 30 min, followed by incubation with UA (600 μM) for 24 h (# P < 0.05 vs. HUA group, n = 6). c ROS production increased in endothelial cells incubated with UA (600 μM) for 24 h (*P < 0.05 vs. control, n = 6), was similar to that in cells treated with pyocyanin, decreased in endothelial cells when pretreated with apocynin/epalrestat (# P < 0.05 vs. HUA group, n = 6), and was reduced significantly in cells pretreated with the AR inhibitor epalrestat (†P < 0.05, Apocynin + HUA group vs. Epalrestat + HUA group, n = 6). d NO levels in supernatant in the Epalrestat + HUA group were enhanced compared to those in the high UA group after endothelial cells were pretreated with epalrestat for 30 min followed by UA (600 μM) for 24 h (*P < 0.05 vs. HUA group, n = 6). e–g Cells were transfected with siRNA or pcDNA3-NOX4, and treated with high uric acid for 24 h. AR siRNA knocked-down AR protein expression and downregulated NOX4 expression (*P < 0.05 vs. siCon group, n = 6). ROS production decreased and NO production increased (*P < 0.05 vs. siCon group, n = 6). However, overexpression of NOX4 did not affect AR. If cells were treated with AR RNAi and overexpressed NOX4, ROS production and NO concentration significantly decreased and increased, respectively, compared to the NOX4 overexpression group (▲P < 0.05, n = 6)