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J.Health Sci., 54(4), 441-449, 2008

Effect of Extract of Pomegranate (Punica granatum L.) on Glycated Protein-iron Chelate-induced Toxicity: An In Vitro Study on Human Umbilical-vein Endothelial Cells

Ikuo Nishigaki,*, a Peramaiyan Rajendran,a Ramachandran Venugopal,a Ganapathy Ekambaram,a Dhanapal Sakthisekaran,band Yutaka Nishigakic

aNPO International Laboratory of Biochemistry, 1-166 Uchide, Nakagawa-ku, Nagoya 454-0926, Japan, bDepartment of Medical Biochemistry, University of Madras, Taramani Campus, Chennai TamilNadu, 600 113, India, and cTokyo Metropolitan Institute of Gerontology, 3-2 Sakaemachi, Itabashi-ku, Tokyo 179-0015, Japan

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.