Chan-Sik Kim

Korea Institute of Oriental Medicine, Bucheon, Gyeonggi Province, South Korea

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Publications (47)111.13 Total impact

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    ABSTRACT: Abstract Many dietary supplements have been sold through advertising their large number of beneficial effects. The aim of this study was to determine whether bilberries (Vaccinium myrtillus) help to prevent diabetes-induced retinal vascular dysfunction in vivo. V. myrtillus extract (VME; 100 mg/kg) was orally administered to streptozotocin-induced diabetic rats for 6 weeks. All diabetic rats exhibited hyperglycemia, and VME did not affect the blood glucose levels and body weight during the experiments. In the fluorescein-dextran angiography, the fluorescein leakage was significantly reduced in diabetic rats treated with VME. VME treatment also decreased markers of diabetic retinopathy, such as retinal vascular endothelial growth factor (VEGF) expression and degradation of zonula occludens-1, occludin and claudin-5 in diabetic rats. In conclusion, VME may prevent or delay the onset of early diabetic retinopathy. These findings have important implications for prevention of diabetic retinopathy using a dietary bilberry supplement.
    International Journal of Food Sciences and Nutrition 01/2015; · 1.20 Impact Factor
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    ABSTRACT: The accumulation of advanced glycation end products (AGEs) is associated with many of the complications of diabetes mellitus, including diabetic retinopathy. AGE-breakers, such as N-phenacylthiazolium and alagebrium, have been proposed as therapeutic agents for reversing the increase in protein crosslinking in diabetes. (-)-Epicatechin is a major dietary flavonoid with a wide range of health-promoting biological activities. The aim of this study was to determine the potential effect of (-)-epicatechin in reducing the burden of AGEs in vitro and in vivo and to evaluate whether the reduced AGE burden could translate into improvement in retinal vascular function in exogenously AGE-injected rats. Glycated human serum albumin was purified from patients with diabetes. The breakdown of the already formed AGEs was studied by treating glycated human serum albumin with (-)-epicatechin. To study the effect of (-)-epicatechin on retinal vascular function, exogenously AGE-injected rats were treated with (-)-epicatechin (50 and 100mg/kg i.p.) for two weeks. Apoptosis of retinal vascular cells was quantified using TUNEL staining. The AGE load in the retinas was determined via immunohistochemical staining and western blot analysis. (-)-Epicatechin was able to break preformed glycated human serum albumin in vitro as well as reduce AGE accumulation in retinas in vivo in a dose dependent manner. In exogenously AGE-injected rats, treatment with (-)-epicatechin was evidenced by an improved retinal vascular apoptosis. AGE burden in retinas was also reduced upon treatment. This study suggests that (-)-epicatechin could represent a valuable drug for the treatment of diabetic retinopathy by reducing the AGE burden. Copyright © 2014. Published by Elsevier B.V.
    European Journal of Pharmacology 12/2014; · 2.68 Impact Factor
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    ABSTRACT: Platelet-derived growth factor-BB (PDGF-BB) is highly expressed in the renal tissues of patients with diabetic nephropathy, and it plays an important role in the initiation and progression of diabetic nephropathy. The aim of this study was to evaluate the protective effects of root of Polygonum cuspidatum extract (PCE) on early renal glomerular proliferation in streptozotocin (STZ)-induced diabetic rats. PCE (100, 350 mg/kg/day) was administered to diabetic rats for 16 weeks. Blood glucose and albuminuria were measured. Renal histology, alpha-smooth muscle actin (alpha-SMA), and proliferating cell nuclear antigen (PCNA) expression levels were also examined. After 16 weeks of treatment with PCE, severe hyperglycemia and albuminuria were observed in the diabetic rats. The expressions levels of alpha-SMA and PCNA proteins were significantly increased in the glomeruli of the diabetic rats. The expression levels of PDGF-BB and its receptor expressions were greatly increased in the glomeruli of the diabetic rats. However, PCE markedly reduced albuminuria in the diabetic rats. PCE inhibited alpha-SMA and PCNA up-regulation and ameliorated PDGF-BB and PEGFR-Ss protein expression in the diabetic rats. In addition, the binding of PDGF-BB/PDGFR-Ss was inhibited by PCE as shown by an in vitro assay. These results suggest that PCE has an inhibitory effect on mesangial proliferation in diabetic renal tissues via the inhibition of the interaction of PDGF-BB with its receptor. PCE may have beneficial effects in preventing the progression of diabetic nephropathy.
    BMC Complementary and Alternative Medicine 12/2014; 14(1):477. · 1.88 Impact Factor
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    ABSTRACT: HL-217 is a new synthetic angiogenesis inhibitor. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. In this study, we examined the mechanism of action and efficacy of topical application of HL-217 on subretinal neovascularization in very low-density lipoprotein receptor knockout (Vldlr−/−) mice. In three-week-old male Vldlr−/− mice, HL-217 (1.5 or 3 mg/ml) was administered twice per day for 4 weeks by topical eye drop instillation. Neovascular areas were then measured. We used a protein array to evaluate the expression levels of angiogenic factors. The inhibitory effect of HL-217 on the PDGF-BB/PDGFRβ interaction was evaluated in vitro. The neovascular area in the Vldlr−/− mice was significantly reduced by HL-217. Additionally, HL-217 decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, HL-217 dose-dependently inhibited the PDGF-BB/PDGFRβ interaction (IC50 = 38.9 ± 0.7 μM). These results suggest that HL-217 is a potent inhibitor of PDGF-BB. HL-217, when applied topically, is an effective inhibitor of subretinal neovascularization due to its ability to inhibit the pro-angiogenic effects of PDGF-BB.
    Biochemical and Biophysical Research Communications 11/2014; · 2.28 Impact Factor
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    ABSTRACT: Advanced glycation end products (AGE) have been implicated in the development of diabetic retinopathy. Characterization of the early stages of diabetic retinopathy is retinal pericytes loss, which is the result of pericytes migration. In this study, we investigated the pathological mechanisms of AGE on the migration of retinal pericytes and confirmed the inhibitory effect of myricetin on migration in vitro and in vivo. Migration assays of bovine retinal pericytes (BRP) were induced using AGE-BSA and phosphorylation of Src, ERK1/2, focal adhesion kinase (FAK-1) and paxillin were determined using immunoblot analysis. Sprague-Dawley rats (6 weeks old) were injected intravitreally with AGE-BSA and morphological and immunohistochemical analysis of p-FAK-1 and p-paxillin were performed in the rat retina. Immunoblot analysis and siRNA transfection were used to study the molecular mechanism of myricetin on BRP migration. AGE-BSA increased BRP migration in a dose-dependent manner via receptor for AGEs (RAGE)-dependent activation of the Src kinase-ERK1/2 pathway. AGE-BSA-induced migration was inhibited by an ERK1/2 specific inhibitor (PD98059), but not by p38 and Jun N-terminal kinase inhibitors. AGE-BSA increased FAK-1 and paxillin phosphorylation in a dose- and time-dependent manner. These increases were attenuated by PD98059 and ERK1/2 siRNA. Phosphorylation of FAK-1 and paxillin were increased in response to AGE-BSA-induced migration of rat retinal pericytes. Myricetin strongly inhibited ERK1/2 phosphorylation and significantly suppressed pericytes migration in AGE-BSA-injected rats. Our results demonstrate that AGE-BSA participated in the pathophysiology of retinal pericytes migration likely through the RAGE-Src-ERK1/2-FAK-1-paxillin signaling pathway. Furthermore, myricetin suppressed phosphorylation of ERK 1/2-FAK-1-paxillin and inhibited pericytes migration.
    Biochemical Pharmacology 10/2014; · 4.65 Impact Factor
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    ABSTRACT: Retinal neovascularization is a common pathology in age-related macular degeneration, retinopathy of prematurity and proliferative diabetic retinopathy. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. Oxygen-induced retinopathy in the mouse is the standard experimental model of proliferative retinopathies. Sipjeondaebo-tang (SDT) is the most widely used traditional herbal formula in East Asia, also known as Shi-Quan-Da-Bu-Tang in Chinese and Juzen-taiho-to in Japanese. SDT has been known to exert anti-angiogenic activities in several tumor models, but the role of SDT in proliferative retinopathies remains unclear. Thus, the object of the present study is to examine the mechanism of action and efficacy of SDT on retinal neovascularization in oxygen-induced ischemic retinopathy (OIR) mice. Neonatal mice at postnatal day 7 (P7) were exposed to 75% concentration of oxygen for 5 days (P7-P12), and then returned to room air from P12 to P17 to induce retinal neovascularization. SDT were administered once per day for 5 consecutive days (P12-P16) by intraperitoneal injection. Retinal neovascularization was measured at P17. We used a protein array to evaluate the expression levels of angiogenic factors. Inhibitory activity of SDT on PDGF-BB/PDGFRβ interaction was evaluated in vitro. Retinal neovascularization in the OIR mice was significantly decreased by SDT. SDT decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, SDT dose-dependently inhibited PDGF-BB/PDGFRβ interaction (IC50 = 388.82 ± 7.31 µg/ml). In conclusion, SDT is a potent inhibitor of retinal neovascularization through inhibiting the pro-angiogenic effect of PDGF-BB.
    The Tohoku Journal of Experimental Medicine 01/2014; 234(3):229-36. · 1.37 Impact Factor
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    ABSTRACT: Declining renal function is commonly observed with age. Obesity induced by a high-fat diet (HFD) may reduce renal function. Korean red ginseng (KRG) has been reported to ameliorate oxidative tissue injury and have an anti-aging effect. This study was designed to investigate whether HFD would accelerate the D-galactose-induced aging process in the rat kidney and to examine the preventive effect of KRG on HFD and D-galactose-induced aging-related renal injury. When rats with D-galactose-induced aging were fed an HFD for 9 wk, enhanced oxidative DNA damage, renal cell apoptosis, protein glycation, and extracellular high mobility group box 1 protein (HMGB1), a signal of tissue damage, were observed in renal glomerular cells and tubular epithelial cells. However, treatment of rats with HFD- plus D-galactose-induced aging with KRG restored all of these renal changes. Our data suggested that a long-term HFD may enhance D-galactose-induced oxidative renal injury in rats and that this age-related renal injury could be suppressed by KRG through the repression of oxidative injury.
    Journal of Nutritional Science and Vitaminology 01/2014; 60(3):159-166. · 0.99 Impact Factor
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    ABSTRACT: Chronic hyperglycemia leads to the formation of advanced glycation end products (AGEs), which accelerates the development of diabetic complications. Previous studies have shown that extract of Cassiae semen (CS), the seed of Cassia tora, has inhibitory activity on AGEs formation in vitro and reduces transforming growth factor-beta1 (TGF-β1) and extracellular matrix protein expression via inhibition of AGEs-mediated signaling in glomerular mesangial cells. In this study, to examine the preventive effects of CS extract on the development of diabetic nephropathy in vivo, streptozotocin (STZ)-injected diabetic rats were orally administered CS extract (200mg/kg body weight/day) for 12 weeks. Serum glucose, triglycerides, and total cholesterol in diabetic rats were significantly higher compared to control rats. CS or aminoguanidine (AG) treatment significantly reduced these factors. Proteinuria and creatinine clearance were also significantly decreased in the CS-treated group compared with the untreated diabetic group. The CS-treated group had significantly inhibited COX-2 mRNA and protein, which mediates the symptoms of inflammation in the renal cortex of diabetic rats. Furthermore, histopathological studies of kidney tissue showed that in diabetic rats, AGEs, the receptor for AGEs, TGF-β1, and collagen IV were suppressed by CS treatment. Our data suggest that oral treatment of CS can inhibit the development of diabetic nephropathy via inhibition of AGEs accumulation in STZ-induced diabetic rats.
    Phytomedicine: international journal of phytotherapy and phytopharmacology 12/2013; · 2.97 Impact Factor
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    ABSTRACT: Loss of blood-retinal barrier (BRB) properties is an important feature in the pathology of diabetic retinopathy. Endothelium integrity is important for the normal vascular function. Litsea japonica (Thunb.) Jussieu is a Korean native plant that is consumed as a vegetable food. In this study, we evaluated the ability of an ethanol extract of L. japonica to prevent retinal vascular leakages in db/db mice, which is an animal model of type II diabetes. L. japonica extracts (LJE, 100 and 250 mg/kg) were administered once a day, orally, for 12 weeks. Vehicle-treated db/db mice exhibited hyperglycemia and retinal vascular leakage. LJE treatment blocked diabetes-induced BRB breakdown and decreased retinal VEGF expression in db/db mice. LJE also inhibited the degradation of occludin, which is an important tight junction protein. These findings support the potential therapeutic usefulness of L. japonica for retinal vascular permeability diseases.
    Endocrine 11/2013; · 3.53 Impact Factor
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    ABSTRACT: Renal lipid accumulation exhibits slowly developing chronic kidney disease and is associated with increased oxidative stress. The impact of exercise on the obese- and oxidative stress-related renal disease is not well understood. The purpose of this study was to investigate whether a high-fat diet (HFD) would accelerate d-galactose-induced aging process in rat kidney and to examine the preventive effect of regular exercise on the obese- and oxidative stress-related renal disease. Oxidative stress was induced by an administration of d-galactose (100 mg/kg intraperitoneally injected) for 9 weeks, and d-galactose-treated rats were also fed with a high-fat diet (60% kcal as fat) for 9 weeks to induce obesity. We investigated the efficacy of regular exercise in reducing renal injury by analyzing Nε-carboxymethyllysine (CML), 8-hydroxygluanine (8-OHdG) and apoptosis. When rats were fed with a HFD for 9 weeks in d-galactose-treated rats, an increased CML accumulation, oxidative DNA damage and renal podocyte loss were observed in renal glomerular cells and tubular epithelial cells. However, the regular exercise restored all these renal changes in HFD plus d-galactose-treated rats. Our data suggested that long-term HFD may accelerate the deposition of lipoxidation adducts and oxidative renal injury in d-galactose-treated rats. The regular exercise protects against obese- and oxidative stress-related renal injury by inhibiting this lipoxidation burden.
    Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry 08/2013; 46(4):111-9. · 1.22 Impact Factor
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    ABSTRACT: Retinal pathogenic angiogenesis in the eyes is a causative factor in retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. This study was designed to examine the pathogenic role of the high-mobility group box-1 (HMGB1) protein and the inhibitory effect of ethyl pyruvate (EP), a well-known antioxidant substance, in retinal pathogenic angiogenesis in mice with oxygen-induced retinopathy (OIR), one of the animal models of proliferative ischemic retinopathy. The OIR mouse model was used for our in vivo studies. The mice were exposed to 75% oxygen from postnatal day 7 (P7) to P11, after which the mice were brought to room air and intraperitoneally injected with EP (50 mg/kg, or 100 mg/kg) for five days. At P17, the mice were perfused with fluorescein isothiocyanate-dextran, and flat-mounted retinas were used to measure nonperfused and neovascular tufts. In OIR mice, an intraperitoneal injection of EP reduced the nonperfused retinal area in the treatment group and significantly reduced the retinal neovascular tufts. In addition, EP inhibited the overexpression of HMGB1 in the retinas of OIR mice. These data suggest that EP could serve as an innovative pharmaceutical agent to prevent retinal neovascularization through inhibiting HMGB1 expression.
    Journal of Diabetes Research 01/2013; 2013:245271. · 3.54 Impact Factor
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    ABSTRACT: Increasing evidence indicates that advanced glycation end products (AGEs) contribute to the pathogenesis of diabetic nephropathy. The aim of this study was to investigate the protective effect of L. japonica extract (LJE) against renal damage in the db/db mouse. LJE (100 or 250 mg/kg per day) was given to diabetic mice for 12 weeks. Body weight, blood glucose levels, glycated hemoglobin (HbA1c) levels, and proteinuria were examined. In in vitro assay of the inhibition of AGE formation, immunohistochemical analysis of podocyte loss and AGE accumulations were performed. In 20-week-old db/db mice, severe hyperglycemia developed, and proteinuria was significantly increased. Diabetes induced markedly morphological alterations to the renal glomerular cells. AGE accumulations and podocyte loss were detected in renal glomeruli. LJE treatment significantly reduced proteinuria and AGE accumulations in diabetic mice. Moreover, the loss of nephrin, an important slit diaphragm component in the kidneys, was restored by LJE treatment. Our studies suggest that LJE might be beneficial for the treatment of diabetic nephropathy. The ability of LJE to attenuate proteinuria and podocyte dysfunction may be mediated by the inhibition of AGE accumulation in the context of diabetic nephropathy in db/db mice.
    Evidence-based Complementary and Alternative Medicine 01/2013; 2013:769416. · 2.18 Impact Factor
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    ABSTRACT: Pyruvate is an endogenous antioxidant substance. The aim of this study was to investigate the protective effects of ethyl pyruvate (EP) on retinal vascular injury in diabetic retinopathy. To investigate the protective effect of EP on vascular cell apoptosis and blood-retinal barrier (BRB) breakage, we have used intravitreally methylglyoxal-(MGO-) injected rat eyes. Apoptosis of the retinal vascular cell that was stimulated by the intravitreal injection of MGO was evidently attenuated by the EP treatment. EP exerts inhibitory effect on MGO-induced vascular cell apoptosis by blocking oxidative injury. In addition, EP treatment prevented MGO-induced BRB breakage and the degradation of occludin, an important tight junction protein. These observations suggest that EP acts through an antioxidant mechanism to protect against oxidative stress-induced apoptosis in retinal vessels.
    Journal of Diabetes Research 01/2013; 2013:460820. · 3.54 Impact Factor
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    ABSTRACT: Cataracts are a major cause of human blindness. Aldose reductase (AR) is an important rate-limiting enzyme that contributes to cataract induction in diabetic patients. Scopoletin is the main bioactive constituent of flower buds from Magnolia fargesii and is known to inhibit AR activity. To assess scopoletin's ability to mitigate sugar cataract formation in vivo, we studied its effects in a rat model of dietary galactose-induced sugar cataracts. Galactose-fed rats were orally dosed with scopoletin (10 or 50 mg/kg body weight) once a day for 2 weeks. Administering scopoletin delayed the progression of the cataracts that were induced by dietary galactose. Scopoletin also prevented galactose-induced changes in lens morphology, such as lens fiber swelling and membrane rupture. Scopoletin's protective effect against sugar cataracts was mediated by inhibiting both AR activity and oxidative stress. These results suggest that scopoletin is a useful treatment for sugar cataracts.
    Evidence-based Complementary and Alternative Medicine 01/2013; 2013:787138. · 2.18 Impact Factor
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    ABSTRACT: KIOM-79, a herbal mixture of parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix, and Euphorbiae radix, has a strong inhibitory effect on advanced glycation end products (AGEs) formation. We investigated the beneficial effects of KIOM-79 on cardiac fibrosis in Zucker diabetic fatty (ZDF) rats. KIOM-79 (50 or 500 mg/kg/day) was orally administered for 13 weeks. AGEs formation and collagen expression in the myocardium were assessed by immunohistochemistry. The expression levels of the receptor for AGEs (RAGE), transforming growth factor- β 1 (TGF- β 1), collagen IV, fibronectin, urotensin II, and urotensin II receptor were examined in the myocardial tissue of ZDF rats. KIOM-79 treatment at 500 mg/kg inhibited the accumulation of AGEs, reduced RAGE mRNA and protein expression, and reduced the upregulation of cardiac fibrogenic factors, such as fibronectin and collagen IV, in heart of ZDF rats. Additionally, KIOM-79 ameliorated urotensin II/receptor gene expression in the cardiac tissue of ZDF rats. Our findings indicate that KIOM-79 diminishes cardiac fibrosis in ZDF rats by preventing AGEs accumulation and RAGE overexpression and by modulating the cardiac urotensin II/receptor pathway, which decreases the amount of profibrotic factors, such as TGF- β 1, fibronectin, and collagen in cardiac tissue.
    Evidence-based Complementary and Alternative Medicine 01/2013; 2013:547653. · 2.18 Impact Factor
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    ABSTRACT: Six new cycloartane-type triterpenes (1-6), 24-methylenecycloartane-3β,6β,7β-triol (1), 24-methylenecycloartane-3β,6β,7β,16β-tetraol (2), 24-methylenecycloartane-3β,6β,16β-triol (3), 24-methylenecycloartane-3β,7β,16β-triol 3-O-β-d-xylopyranoside (4), 24-methylenecycloartane-3β,6β,16β-triol 3-O-β-d-xylopyranoside (5), and 24-methylenecycloartane-3β,6β,7β-triol 3-O-β-d-xylopyranoside (6), were isolated from the leaves of Homonoia riparia, together with one known compound, 24-methylenecycloartane-3β,6β,7β,16β-tetraol 3-O-β-d-xylopyranoside (7). The structures of the new triterpenes were established by spectroscopic studies and from chemical evidence, and the inhibitory effects of compounds 1 and 3-7 on VEGF-induced vascular permeability were examined in vivo in rats using the Miles assay. In addition, the inhibitory effect of 7 on VEGF-induced tube formation by HUVECs in vitro was investigated.
    Journal of Natural Products 06/2012; 75(7):1312-8. · 3.95 Impact Factor
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    ABSTRACT: Retinal pericyte loss is one of the histopathological hallmarks of early diabetic retinopathy. Puerarin (4'-7-dihydroxy-8-beta-d-glucosylisoflavone), which is an isoflavone-C-glucoside, causes various pharmacological effects that include antihyperglycemic and anti-inflammatory activities. In the present study, we determined the efficacy and possible mechanism of puerarin on the advanced glycation end product (AGE)-modified bovine serum albumin (BSA)-induced apoptosis of cultured bovine retinal pericytes and rat retinal pericytes in intravitreally AGE-modified rat serum albumin (RSA)-injected eyes. Puerarin significantly inhibited pericyte apoptosis, the generation of reactive oxygen species (ROS), and NADPH oxidase activity by inhibiting the phosphorylation of p47phox and Rac1 which were induced by the AGE-BSA treatment. The puerarin treatment markedly suppressed the activation of nuclear factor-kappaB (NF-κB). In addition, the in vivo apoptosis of the retinal pericyte of rats that was stimulated by the intravitreal injection of AGE-RSA was evidently attenuated by the puerarin treatment. These results demonstrate that puerarin may exert inhibitory effects on AGE-induced pericyte apoptosis by interfering with the NADPH oxidase-related ROS pathways and blocking NF-κB activation, thereby ameliorating retinal microvascular dysfunction.
    Free Radical Biology and Medicine 05/2012; 53(2):357-65. · 5.27 Impact Factor
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    ABSTRACT: One of the early signs of diabetic retinopathy is the alteration of the blood-retinal barrier (BRB), which may involve the breakdown of endothelial cell tight junctions. Methylglyoxal (MGO) is a cytotoxic metabolite that is produced from glycolysis in vivo. Elevated levels of MGO are observed in a number of pathological conditions, including neurodegenerative disorders and diabetic complications. Herein, we hypothesize that increased levels of MGO disrupt the tight junction protein known as occludin protein by matrix metalloproteinases (MMPs), leading to breakage of the BRB. MGO was intravitreally injected into eyes of rats. BRB leakage, MMPs activity, and occludin were investigated in intravitreally MGO-injected eyes. When normoglycemic rats were intravitreally injected with 400 μM MGO, there was widespread leakage of fluorescein isothiocyanate-bovine serum albumin (FITC-BSA) from the retinal vasculature when compared to control retinas. In addition, MGO-injected retinas demonstrated increases of both activity and expression of MMP-2 and MMP-9, and the degradation of occludin was found in the MGO-injected retinas. The results suggest that the activation of MMPs by elevated levels of MGO in the retina may facilitate an increase in vascular permeability by a mechanism involving proteolytic degradation of occludin. These findings may have implications for the role of MGO in the pathogenesis of diabetic retinopathy.
    Albrecht von Graæes Archiv für Ophthalmologie 01/2012; 250(5):691-7. · 1.93 Impact Factor
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    ABSTRACT: KIOM-79 is an herbal mixture of parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix. In the present study, we determined the efficacy and possible mechanism of KIOM-79 on the advanced glycation end product (AGE)-modified bovine serum albumin (BSA)-induced apoptosis of cultured bovine retinal pericytes and rat retinal pericytes in Zucker diabetic fatty (ZDF) rats. Seven-week-old male ZDF rats were treated with KIOM-79 (50 mg/kg body weight) once a day orally for 13 weeks. KIOM-79 significantly inhibited pericyte apoptosis which were induced by the AGE-BSA treatment. The KIOM-79 treatment markedly suppressed the activation of nuclear factor-kappaB (NF-κB) through the inhibition of inhibitory κB kinase complex. In addition, the oral administration of KIOM-79 inhibited the changes in retinal vasculature (vascular hyperpermeability, acellular capillary). KIOM-79 strongly inhibited pericyte apoptosis, NF-κB activation and the expression of pro-apoptotic Bax and tumor necrosis factor-α. Our results suggest that KIOM-79 may exert inhibitory effects on AGE-induced pericyte apoptosis by blocking NF-κB activation, thereby ameliorating retinal microvascular dysfunction.
    PLoS ONE 01/2012; 7(8):e43591. · 3.53 Impact Factor
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    ABSTRACT: Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT) rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day) was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c), and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG) levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.
    Experimental Diabetes Research 01/2012; 2012:210821. · 3.54 Impact Factor