Abstract
Propofol is a widely used intravenous anesthetic agent with antioxidant/antiapoptotic properties. Aldose reductase (AR) has been implicated in oxidative stress and apoptosis in endothelial cells. AR inhibition may protect cells from cardiovascular injury. Although the cytoprotective effect of propofol against hydrogen peroxide (H2O2)-induced injury has been widely studied, there is no information about the effects of propofol on AR. We therefore investigated the effect of propofol on H2O2-mediated injury and on aldose reductase expression. We found that propofol protected HUVECs against H2O2-induced damage and apoptosis and ameliorated AR expression induced by H2O2. Propofol also inhibited H2O2-induced p38 MAPK, JNK and Akt phosphorylation. Epalrestat (an AR inhibitor) or ablation of AR siRNA had a similar effect to propofol. The results suggest that propofol may be a preemptive anesthetic in patients with cardiovascular disease and inhibition of AR might be a new cytoprotective pathway for propofol.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aldehyde Reductase / biosynthesis
-
Aldehyde Reductase / metabolism*
-
Anesthetics, Intravenous / pharmacology*
-
Apoptosis / drug effects
-
Free Radical Scavengers / pharmacology*
-
Human Umbilical Vein Endothelial Cells / drug effects*
-
Human Umbilical Vein Endothelial Cells / enzymology
-
Humans
-
Hydrogen Peroxide / antagonists & inhibitors*
-
Hydrogen Peroxide / toxicity*
-
MAP Kinase Kinase 4 / metabolism
-
Malondialdehyde / metabolism
-
Oncogene Protein v-akt / metabolism
-
Oxidants / toxicity*
-
Propofol / pharmacology*
-
RNA, Small Interfering / pharmacology
-
Rhodanine / analogs & derivatives
-
Rhodanine / pharmacology
-
Signal Transduction / drug effects
-
Thiazolidines / pharmacology
-
p38 Mitogen-Activated Protein Kinases / metabolism
Substances
-
Anesthetics, Intravenous
-
Free Radical Scavengers
-
Oxidants
-
RNA, Small Interfering
-
Thiazolidines
-
epalrestat
-
Malondialdehyde
-
Rhodanine
-
Hydrogen Peroxide
-
Aldehyde Reductase
-
Oncogene Protein v-akt
-
p38 Mitogen-Activated Protein Kinases
-
MAP Kinase Kinase 4
-
Propofol