- Effect of Advanced Glycation End Products on Rat Aortic Vascular Smooth Muscle Cells.
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Jin Young Song, Sung Hee Ihm, Ji Young Suh, Young Joong Cho, Hyung Joon Yoo, Sung Woo Park, Ja Hei Ihm
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Korean Diabetes J. 2002;26(2):91-99. Published online April 1, 2002
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 Abstract
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- BACKGROUND
Diabetes mellitus is an epidemiologically proven risk factor for atherosclerosis. Advanced glycation end products (AGE) have been implicated in the pathogenesis of many diabetic vascular complications. AGE not only change the physicochemical properties of proteins, but also induce a wide range of cell-mediated responses. However, biological effects of AGE on the vascular smooth muscle cells (VSMCs) have not been fully explained despite of presence of an AGE-receptor on the VSMCs. METHODS: In order to test whether AGE promotes atherosclerosis by stimulation of the growth promoting signal transduction pathways in the VSMCs, the proliferation of rat aortic VSMCs cultured in the presence of AGE-BSA with/without anti-AGE antibodies, the MAP kinase inhibitor and antioxidants was measured. The VSMCs (1 x 104 cells in 24-well plates) isolated from the aorta of Sprague-Dawley rats were incubated for 48 hours and the proliferation was assessed by a MTT assay. RESULTS: AGE-BSA increased the proliferation of rat aortic VSMCs by 1.5~1.6 fold at the g/mL level. The stimulatory effect of AGE-BSA (5 microgram/mL) was blocked by the anti-AGE antibodies (100 microgram/mL). PD98059 at 50 M inhibited the AGE - BSA - induced VSMC proliferation, suggesting that MAP kinase activation might be responsible for the proliferative response of the VSMCs to AGE. AGE - BSA - induced VSMC proliferation was also attenuated by N-acetylcysteine (1 micro M) and butylated hydroxyanisole (10 micro M), implying that increased intracellular oxidative stress might be also involved in the proliferative response to AGE. CONCLUSION: These results suggest AGE play a role in diabetic atherosclerosis by stimulating of the growth promoting signal transduction pathways in the VSMCs.
- Effect of Red Ginseng Extract on Lipid Peroxidation in Streptozotocin-induced Diabetic Rats.
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Hee Jong Jin, Sung Hee Ihm, Ja Hei Ihm
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Korean Diabetes J. 2001;25(5):374-383. Published online October 1, 2001
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Abstract
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- BACKGROUND
Diabetes mellitus is postulated to be associated with increased oxidative stress and lipid peroxidation which may contribute to vascular complications. Recently ginseng (Panax) has been shown to have an antioxidant effect by enhancing nitric oxide synthesis in endothelial cells and by directly scavenging hydroxyl radicals. It is unknown whether ginseng might act as an antioxidant against lipid peroxidation in diabetes. METHODS: We studied the in vitro effect of red ginseng extract on lipid peroxidation employing phospholipid liposome and low-density lipoprotein (LDL) as a model system. To investigate the in vivo effect on lipid peroxidation in diabetes, we administered red ginseng extract (1 g/L in drinking water) to streptozotocin (STZ)- induced diabetic rats for 12 weeks and measured lipid peroxidation products in plasma, liver, kidneys and heart. RESULTS: The Fe(3+)- or Cu(2+)- mediated lipid peroxidation in phospholipid liposome and LDL, measured by the concentration of TBARS, was inhibited in the presence of red ginseng extract. MDA level in plasma measured by HPLC was higher in STZ-induced diabetic rats than in control rats. Plasma MDA level was lower by 41% in red ginseng-treated diabetic rats than in untreated diabetic rats. Tissue MDA levels measured by TBA method in liver, kidneys and heart were higher in STZ-induced diabetic rats than in control rats. In red ginseng-treated diabetic rats tissue MDA levels were lower by 14~30% than in untreated diabetic rats. CONCLUSION: We observed that red ginseng extract has an effect in inhibiting lipid peroxidation both in vitro and in STZ-induced diabetic rats. These results suggest that red ginseng might have a beneficial effect in diabetes as an antioxidant against lipid peroxidation and diabetic vascular complications.
- Effect of Aminoguanidine on Lipid Peroxidation in Streptozotocin-induced Diabetic Rats.
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Kwon Yeop Lee, Sung Hee Ihm, Hyung Joon Yoo, Sung Woo Park, Ja Hei Ihm
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Korean Diabetes J. 1997;21(4):372-380. Published online January 1, 2001
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Abstract
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- BACKGROUND
Diabetes mellitus is postulated to be associated with increased lipid peroxidation which may contribute to vascular complications. One potential mechanism of the increased lipid peroxidation in diabetes is lipid-linked advanced glycosylation and oxidation. Aminoguanidine(AMGN), the prototype inhibitor of advanced glycosylation end-product formation, has been recently shown to prevent oxidative moditication of LDL in vitro at moderate concentration. It is unknown whether AMGN might act as an anti-oxidant against lipid peroxidation under hyperglycemia in vivo. METHODS: To investigate the in vivo effect of AMGN on lipid peroxidation in diabetes, we administered AMGN(1 g/L in drinking water) or vitamin E (400mg/day, 5 days/week) to streptozotocin(STZ)-induced diabetic rats for 9 weeks and measured plasma lipid hydroperoxides by ferrous oxidation with xylenol orange II method and RBC membrane malon-dialdehyde(MDA) by thiobarbituric acid method. RESULTS: Plasma lipid hydroperoxide level was higher in STZ-induced diabetic rats than in control rats(7.53+/-2.03 vs.5.62+/-0.44*pmol/L). RBC membrane MDA was also higher in STZ-induced diabetic rats than in control rats(2.67+/-0.46 vs. 1.81+/-0.19* nmol/mL). Plasma lipid hydroperoxide level was lower in AMGN-treated(6.23+/-0.59*umol/L) and vitamin E-treated(5.29+/-0.27*umol/L) diabetic rats than in untreated diabetic rats. RBC membrane MDA was also lower in AMGN-treated(1.93+/-0.12""'nmol/ mL) diabetic rats than in untreated diabetic rats. There was no significant difference in plasma glucose, triglyceride levels among diabetic groups(Mean +/-S.D; *, P<0.05 vs. untreated STZ-induced diabetic rats; n=8-14/group). CONCLUSION: Although the mechanisms of action of AMGN on lipid peroxidation in vivo should be studied further, these results suggest that AMGN might have an additional beneficial effect as an antioxidant against lipid peroxidation in prevention trial for diabetic vascular complications.
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