• The Korean Journal of Physiology and Pharmacology
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• v.12 no.4
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• pp.165-170
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• 2008

In the present study, we aimed to identify the synergistic effects of concurrent treatment of low concentrations of cilostazol and probucol to inhibit the oxidative stress with suppression of inflammatory markers in the cultured human coronary artery endothelial cells (HCAECs). Combination of cilostazol (0.3${\sim}3{\mu}$M) with probucol (0.03${\sim}0.3{\mu}$M) significantly suppressed TNF-${\alpha}$-stimulated NAD(P)H-dependent superoxide, lipopolysaccharide (LPS)-induced intracellular reactive oxygen species (ROS) production and TNF-${\alpha}$ release in comparison with probucol or cilostazol alone. The combination of cilostazol (0.3${\sim}3{\mu}$M) with probucol (0.1${\sim}0.3{\mu}$M) inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) more significantly than did the monotherapy with either probucol or cilostazol. In line with these results, combination therapy significantly suppressed monocyte adhesion to endothelial cells. Taken together, it is suggested that the synergistic effectiveness of the combination therapy with cilostazol and probucol may provide a beneficial therapeutic window in preventing atherosclerosis and protecting from cerebral ischemic injury.

• Nutritional Sciences
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• v.6 no.2
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• pp.94-99
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• 2003

The purpose of this study was to investigate in vivo lipid peroxidation in rats under conditions of streptozotocin-induced oxidative stress and the antioxidant effects of probucol. In vivo lipid peroxidation was observed by measuring low molecular weight aldehydes and related carbonyl compounds in rat urine. Three groups of male Wistar rats weighing 165-190 g were used: normal (N), streptozotocin-induced oxidative stress (OS) and oxidative stress plus probucol treatment (P). following streptozotocin treatment of the rats, a variety of secondary lipid peroxidation products were increased. The levels of butanal, hexanal, hex-2-enal, kept-2-enal, octanal, non-2-enal, deca-2,4-dienal, 4-hydroxyhex-2-enal, 4-hydroxyno n-2-enal, malondi aldehyde(MDA), and unknown carbonyl compounds were significantly increased in the oxidative stress group compared to the control group. Treatment with probucol resulted in significant decreases in buoal, hexanal, hex-2-enal, octanal, deca-2,4-dienal, 4-hydroxyhex-2-enal, MDA and unknown carbonyl compounds. Hept-2-enal, hepta-2,4-dienal and non-2-enal appeared to have a tendency to decrease due to pobucol treatment.

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.277.2-277.2
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• 2000

• Biotechnology and Bioprocess Engineering:BBE
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• v.5 no.5
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• pp.366-371
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• 2000

The aim of this study was to investigate the efficiency of the pentagalloic acid compound in inhibiting the metal ions and cell lines that mediate in low density lipoprotein (LDL) oxidation. Pentagalloic acid prolonged the lag time preceeding the onset of conjugated diene formation. In chemically induced LDL oxidation by Cu$^2$(sup)+ plus hydrogen peroxide or peroxyl radical generated by 2, 2-azo-vis (2-amidino propane) hydrochloride (AAPH), pentagalloic acid inhibited LDL oxidation as monitored by measuring the thiobarbituric acid reactive substances(TBARS), malondialdehyde(MDA), and gel electrophoretic mobility. The physiological relevance of the antioxidative activity was validated at the cellular level where pentagalloic acid inhibited mouse macrophage J774 and endothelial cell-mediated LDL oxidation. When compared with several other antioxidants, pentagalloic acid showed a much higher ability than naturally occuring antioxidants, ${\alpha}$-tocopherol and ascorbic acid, and the synthetic antioxidant, probucol.

• Clinical and Experimental Pediatrics
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• v.55 no.10
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• pp.371-376
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• 2012

Purpose: Puromycin aminonucleoside (PAN) specifically injures podocytes, leading to foot process effacement, actin cytoskeleton disorganization, and abnormal distribution of slit diaphragm proteins. p130Cas is a docking protein connecting F-actin fibers to the glomerular basement membrane (GBM) and adapter proteins in glomerular epithelial cells (GEpCs; podocytes). We investigated the changes in the p130Cas expression level in the PAN-induced pathological changes of podocytes in vitro. Methods: We observed changes in the p130Cas expression in cultured rat GEpCs and mouse podocytes treated with various concentrations of PAN and antioxidants, including probucol, epigallocatechin gallate (EGCG), and vitamin C. The changes in the p130Cas expression level were analyzed using confocal immunofluorescence imaging, Western blotting, and polymerase chain reaction. Results: In the immunofluorescence study, p130Cas showed a diffuse cytoplasmic distribution with accumulation at distinct sites visible as short stripes and colocalized with P-cadherin. The fluorescences of the p130Cas protein were internalized and became granular by PAN administration in a dose-dependent manner, which had been restored by antioxidants, EGCG and vitamin C. PAN also decreased the protein and mRNA expression levels of p130Cas at high doses and in a longer exposed duration, which had been also reversed by antioxidants. Conclusion: These findings suggest that PAN modulates the quantitative and distributional changes of podocyte p130Cas through oxidative stress resulting in podocyte dysfunction.

• Journal of Food Hygiene and Safety
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• v.26 no.3
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• pp.254-259
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• 2011

Growing evidence indicates that oxidized low density lipoprotein (LDL) may promote atherogenesis. Therefore, inhibition of LDL oxidation may impede this process. The inhibitory effected on the susceptibility of human LDL to $Cu^{2+}$ or macrophages induced oxidation was investigated by monitoring thiobarbituric acid reactive substances(TBARS). Organosulfur compounds of garlic oil contains diallyldisulfide, diallyltrisulfide, diallyltetrasulfide, and diallyl pentasulfide in order. Garlic oil inhibited LDL oxidation by $Cu^{2+}$, or macrophages in a dose dependently, with a 20~60 ${\mu}g$, as increased TBARS assay. Garlic oil, at 60 ${\mu}M$, almost completely inhibited macrophages induced increase in electrophoretic mobility of LDL. When compared with several other antioxidants, probucol showed highest ability, and then garlic oil showed a much higher ability than natural occurring antioxidants, ${\alpha}$-tocopherol and ascorbic acid. The results suggested that garlic oil might play the inhibitory effects in the process of LDL oxidation.

• Clinical and Experimental Pediatrics
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• v.51 no.1
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• pp.54-61
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• 2008

Purpose : This study was designed to clarify the mechanism of proteinuria in nephrotic syndrome patients by using puromycin aminonucleoside (PAN) nephrosis model. Methods : Following administration of various concentrations of PAN and antioxidants we observed the changes of podocyte cytoskeletons in cultured rat glomerular epithelial cells (GEpC) by method of scanning electron microscope, reactive oxyten species (ROS) analysis, permeability assay, confocal microscope, and Western blot assay. Results : PAN not only induced the ultrastructural changes of GEpC, such as shortening and fusion of microvilli, but also separated the intercellular gaps and linear ZO-1. PAN induced oxidative stresses in time and dose dependent manners and increases of intercellular permeability in anti-oxidants inhibitable manners. High concentration of PAN induced not only actin polymerization and disorganization, but also the conglomerulation and internal dislocation of ${\alpha}-actinin$ protein. The intensities of fluorescences of ZO-1 protein were diminished and internalized by PAN in a dose-dependent manner, which were inhibited by anti anti-oxidants. Conclusion : PAN induced the changes of podocytes cytoskeleton and junctional barriers by way of increasing ROS in GEpC that resulted in increasing their permeability in a antioxidatn-inhibitable manner. Glomerular hyperpermeability induced by PAN mediateing through oxidative stresses is thought to take part in the mechanism of proteinuria in nephrotic syndrome.

• Journal of Life Science
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• v.14 no.1
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• pp.180-187
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• 2004

Crowing evidence indicates that oxidized low density lipoprotein (LDL) nay promote atherogenesis. Therefore, inhibition of LDL oxidation may impede this process. The effect of geraniin on the susceptibility of human low density lipoprotein (LDL) to macrophages-induced oxidation was investigated by monitoring a thiobarbiruric acid reactive substrance (TBARS). The antioxidative activity of geraniin was higher than that of $\alpha$-tocopherol on low density lipoprotein (LDL) oxidation by thiobarbituric acid reactive substance (TBARS). Geraniin inhibited the C $u^{2+}$ mediated oxidation of human LDL in a dose dependent manner at concentration of 50 and 100 $\mu\textrm{g}$/mL. Geraniin, almost completely inhibited the macrophages mediated LDL oxidation in electrophoretic mobility and conjugate diene of LDL oxidation. Also, geraniin almost completely inhibited 0$_2$$^{[-10]}$ at concentration of 100 $\mu\textrm{g}$/mL. The physiological relevance of the antioxidative activity was validated at the cellular level where geraniin inhibited endothelial cell mediated LDL oxidation, When compound with several other antioxidants geraniin showed a high activity equal to natural antioxidants, $\alpha$-tocopherol and ascorbic acid, and the synthetic antioxidant, protocol. These results indicate that geraniin might play a protective antioxidant effects on LDL, probably affecting both the structural properties of macrophage and endothelial cell for the LDL oxidation..