2008 Volume 54 Issue 4 Pages 441-449
The binding of advanced glycation endproducts (AGEs) to a cell-surface receptor for AGEs (RAGE) induces the formation of reactive oxygen species (ROS), which have been causally implicated in the pathogenesis of diabetic vascular complications. Pomegranate fruit extract (PFE) contains, a naturally occurring polyphenolic compound reported to possess potent radical-scavenging and antioxidant properties and to display significant cardiovascular protective action. In this study, we investigated whether PFE could inhibit glycated protein-iron chelate-induced toxicity by interfering with ROS generation in human umbilical-vein endothelial cells (HUVEC). Glycated fetal bovine serum (GFBS) was prepared by incubating fetal bovine serum (FBS) with high-concentration glucose. Stimulation of cultured HUVECs with 50 mM 1 ml of GFBS significantly enhanced lipid peroxidation and decreased antioxidant enzyme activities and levels of phase II enzymes. However, preincubation of the cultures with PFE resulted in a marked decrease in the level of lipid peroxide (LPO) and increase in the levels of antioxidant enzymes in a PFE concentration-dependent manner. These results demonstrate that PFE could inhibit LPO and enhance the antioxidant enzyme status in GFBS-iron chelate exposed endothelial cells by suppressing ROS generation, thereby limiting the effects of the AGE-RAGE interaction. Hence, PFE may have therapeutic potential in the prevention and treatment of vascular complications in diabetic patients.