• Molecules and Cells
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• v.38 no.4
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• pp.285-296
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• 2015

Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, the complication of diabetes in the kidney. NADPH oxidases of the Nox family, and in particular the homologue Nox4, are a major source of reactive oxygen species in the diabetic kidney and are critical mediators of redox signaling in glomerular and tubulointerstitial cells exposed to the diabetic milieu. Here, we present an overview of the current knowledge related to the understanding of the role of Nox enzymes in the processes that control mesangial cell, podocyte and tubulointerstitial cell injury induced by hyperglycemia and other predominant factors enhanced in the diabetic milieu, including the renin-angiotensin system and transforming growth factor-${\beta}$. The nature of the upstream modulators of Nox enzymes as well as the downstream targets of the Nox NADPH oxidases implicated in the propagation of the redox processes that alter renal biology in diabetes will be highlighted.

• Journal of Nutrition and Health
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• v.34 no.7
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• pp.734-740
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• 2001

The purpose of this study was to investigate the effect of green tea catechins on the antioxidative defense enzyme activity of kidney in diabetic rats. Sprague-Dawley male rats weighting 100$\pm$10g were randomly assigned to one normal and three STZ-induced diabetic groups; catechin free diet(DM-0C group), 0.25% catechin diet(DM-0.25C group) and 0.5% catechin diet(DM-0.5C group). Diabetes was induced by intravenous of 55mg/Kg body weight of STZ in sodium citrate buffer(pH 4.3) after 4 weeks feeding of experimental diets. Rats were sacrified at the 6th day of diabetic states. Superoxide dismutase(SOD) activity in kidney was decreased by 25% and 20% in DM-0C and DM-0.25C groups compared with normal group, DM-0.5C group was not significantly different when compared with normal group. Glutathione peroxidase(GSHpx) activity in kidney was were no significant differences the diabetic groups compared to normal group. Xanthin oxidase(XOD) activity was increased by 110% and 63% in DM-0C and DM-0.25C groups compared with normal group, DM-0.5C group was not significantly different when compared with normal group. The contents of superoxide radical(O$_2$)in kindney were 116% and 33%, respectively, higher in DM-0C and DM-0.25C groups than normal group. DM-0.5C group and normal groups were similar levels in their superoxide radical contents of kidneys. Levels of TBARS(thiobarbituric acid reactive substance) in kidney were increased by 62% in DM-0C group, when compared with normal group, but those of DM-0.5C group were similar to that of normal groups. These results indicate that free radical generation system was weakened and free radical scavenger system was enhance in kidney of STZ-induced diabetics rats by dietary catechin. Thereby it may reduce renal disorders such as oxidative damage and aging of tissue.

• Journal of the Korean Society of Food Science and Nutrition
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• v.28 no.3
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• pp.654-662
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• 1999

The purpose of this study was to investigate the effects of vitamin E on the antioxidative defense system of kidney in streptozotocin induced diabetic rats. Sprague Dawley male rats weighing 100$\pm$10g were randomly assigned to one normal and three STZ induced diabetic groups, which were subdivided into vitamin E free diet(DM 0E group), 40mg vitamin E per kg diet(DM 40E group) and 400mg vitamin E per kg diet(DM 400E group). Vitamin E level of normal group was 40 mg per kg diet. Diabetes was experimentally induced by intravenous injection of 55mg/kg of body weight of streptozotocin(STZ) in citrate buffer(pH 4.3) after 4 weeks feeding of experimental diets. Animals were sacrificed at the 6th day of diabetic states. There were no significant on body weights, food intakes, and food efficiency ratio before the diabetic occurrence. But after the injection of STZ, body weights and food efficiency ratios were significantly decreased and the food intakes was increased. Kidney weights were significantly increased in diabetic groups compared to normal group. However, there were no significant differences among the diabetic groups. Plasma insulin levels of diabetic groups were significantly decreased, whereas, blood sugar levels were increased compared to that of normal group. There were no significant differences among diabetic groups in plasma insulin and glucose levels. Activities of superoxide dismutase(SOD) in DM 0E and DM 40E groups were signi ficantly decreased by 33% and 27%, respectively, compared to normal group. But that of DM 400E group was increased by 35% compared to DM 0E group. Activity of glutathione peroxidase(GSHpx) in DM 0E group was decreased by 20% compared with normal group. GSHpx activity in DM 400E group was increased by 29% compared to normal group. The contents of vitamin E in kidney were 58% and 49% lower in DM 0E and DM 40E group, respectively, than normal group. There was no significant difference in renal vitamin E contents between DM-400E group and normal group. The contents of superoxide radical(O2 ) in kidney were 150% and 98%, respectively, higher in DM 0E and DM 40E groups than normalgroup. DM 400E and normal groups were similar levels in their superoxide radical contents of kidneys. These results indicate that vitamin E functioned as chain breaking antioxidant in kidney such as in other tissues.

• Journal of Ginseng Research
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• v.37 no.2
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• pp.187-193
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• 2013

The effect of Korean red ginseng (KRG) on diabetic renal damage was investigated using streptozotocin (STZ)-induced diabetic rats. The diabetic rats showed loss of body weight gain, and increases in kidney weight and urine volume, whereas the oral administration of KRG at a dose of 100 or 250 mg/kg of body weight per day for 28 d prevented these diabetes-induced physiological abnormalities. Among the kidney function parameters, elevated plasma levels of urea nitrogen and creatinine in diabetic control rats tended to be lowered in KRG-treated rats. In addition, administration of KRG at a dose of 100 mg/kg body weight in the diabetic rats showed significant decreases in serum glucose and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), implying that KRG might prevent the pathogenesis of diabetic complications caused by impaired glucose metabolism and oxidative stress. KRG also significantly reduced advanced glycation end product (AGE) formation and secretion from kidney of diabetic rats. Furthermore, KRG decreased the levels of N-(carboxymethyl) lysine and expression of AGE receptor. KRG also reduced the overexpression of cyclooxygenase-2 and inducible nitric oxide synthase in the kidney via deactivation of nuclear factor-kappa B. We also found that KRG prevented STZ-induced destruction of glomerular structure and significantly suppressed high glucose-induced fibronectin production. Taken together, KRG ameliorates abnormalities associated with diabetic nephropathy through suppression of inflammatory pathways activated by TNF-${\alpha}$ and AGEs. These findings indicate that KRG has a beneficial effect on pathological conditions associated with diabetic nephropathy.

• The Journal of Korean Medicine
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• v.37 no.2
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• pp.62-75
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• 2016

Objectives: This study examined whether Lycii Radicis Cortex has an inhibitory effect on inflammatory response through an oxidative stress and advanced glycation endproducts (AGEs)-mediated pathway in streptozotocin (STZ)-induced type 1 diabetic rats. Methods: Lycii Radicis Cortex was orally administered to STZ-induced diabetic rats in doses of 80 or 160 mg/kg body weight/day for 2 weeks, and its effects were compared with those of diabetic control and normal rats. Results: The administration of Lycii Radicis Cortex decreased the elevated serum urea nitrogen and renal reactive oxygen species (ROS), and reduced the increased AGEs in the serum and kidney. The elevated protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits in the kidney of diabetic control rats were significantly decreased after Lycii Radicis Cortex treatments. Moreover, the kidney of diabetic rats exhibited the up-regulation of receptor for AGEs (RAGE) and AGEs-related proteins; however, Lycii Radicis Cortex treatment also significantly reduced those expressions (excepted RAGE). In addition, the diabetic rats exhibited an up-regulation of the expression of proteins related to inflammation in the kidney, but Lycii Radicis Cortex administration reduced significantly the expression of the inflammatory proteins through the nuclear factor-kappa B (NF-${\kappa}B$) and activator protein-1 (AP-1) pathways. Conclusions: This study provides scientific evidence that Lycii Radicis Cortex exerts the antidiabetic effect by inhibiting the expressions of AGEs and NF-${\kappa}B$ in the STZ-induced diabetic rats.

• Biomedical Science Letters
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• v.14 no.4
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• pp.211-218
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• 2008

The purpose of this study was to investigate the effects of dietary Chungkookjang (Korean fermented soybean) powder on blood glucose level, lipid profiles, antioxidant enzymes activities and histological changes in kidney of streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats of three groups including nondiabetic group fed normal diet (NC), diabetic group fed normal diet (DC) and diabetic group fed Chungkookjang diet (DCH; 100 g/kg diet) were reared for 8 weeks. The serum glucose, triglycelide and total lipid levels in the DCH group were significantly lower (P<0.05) than the DC group. The renal xanthine oxidase, catalase and glutathione S-transferase activities in the DC group were significantly higher than the NC group. The xanthine oxidase, superoxide dismutase and glutathione S-transferase activities in the DCH group were significantly lower than the DC group (P<0.05). Tubular epithelial change, such as Armanni-Ebstein cells, was significantly reduced in the DCH group compared to the DC group. In conclusion, these results indicated that Chungkookjang supplement seems to be beneficial to correct the hyperglycemia and hyperlipidemia as well as to protect kidney against diabetic changes.

• Preventive Nutrition and Food Science
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• v.16 no.3
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• pp.272-277
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• 2011

The hypoglycemic effects of germinated rough rice extract in streptozotocin (STZ)-induced diabetic rats were investigated. Weight gain was significantly lower in the diabetic groups than in the normal control (NC); however, they were higher in the 1% and 3% diabetic groups given germinated Goami2 rough rice extract (DM-3%GGRRE) than in the diabetic control (DC). While food intake in all diabetic groups was significantly higher than that of the NC, there was no significant difference among all diabetic groups. The weight percentages of liver and kidney in all diabetic groups were significantly higher than that of the NC. In terms of blood glucose, the diabetic group showed about a three times larger value than the normal group. Moreover, in the 3% germinated rough rice extract group, the blood glucose level became lowered. The levels of alanine transaminase, aspartate transaminase, blood urea nitrogen, creatinine phosphokinsae, and creatinine increased in general with the induction of diabetes using STZ; however, the 3% GGRRE-treated group displayed a significant decrease in these levels compared to the diabetic group. The results show that the 3% GGRRE, rather than the 1% GGRRE, was considerably more effective at reducing blood glucose and improving impaired glucose tolerance, suggesting the germinated rice extracts may play a role in preventing liver and kidney damage.

• Journal of the Korean Society of Food Culture
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• v.22 no.1
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• pp.140-148
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• 2007

Diabetic nephropathy has been increasing, although blood glucose and blood pressure can be controlled by angiotensin converting enzyme(ACE) or advanced glycosylation end products(AGE) inhibitors in the diabetic patients. We investigated the effect of dietary supplementation of sea tangle on the blood glucose, and pathological scoring of diabetic kidneys in the streptozotocin(STZ) induced diabetic rats. Male Sprague-Dawley rats were divided into normal rats fed control diet and diabetic rats fed control diet or control diet supplemented with powder or oater extract of sea tangle. Diabetes was induced by a single injection of STZ(60mg/kg, ip) in citrate buffer. The animals were fed the experimental diet and water for 13 weeks. Dietary supplementation of sea tangle decreased blood glucose in the diabetic rats. However, dietary supplementation of sea tangle did not affect the antioxidant enzyme activities, MDA content and pathology of diabetic kidneys. These results indicate that decreased blood glucose by sea tangle could not delay the progression of diabetic kidney disease.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.917-922
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• 2002

We investigated the long term effects of Sopungsungi-won (SP), a Korean traditional formula used for senile constipation and diabetes mellitus, on the development of diabetic nephropathy (DN) in Zucker diabetic fatty (ZDF) rats. ZDF rats were fed regular laboratory chow mixed with SP or rosiglitazone (RSG) for an 8-week period. Kidney hypertrophy was developed with increasing plasma glucose level, and glomerular hypertrophy was improved by 22% and 45% in SP- and RSG-treated rats, respectively. Urinary glucose and albumin excretions were also significantly lower in SP-treated rats than in ZDF control rats. Activation of the mitogen-activated protein kinase (MAPK)-transforming growth factor ${\beta}1$ (TGF ${\beta}1$)-fibronectin pathway in kidney, responsible for glomerular dysfunction, was markedly blunted by SP treatment in a dose dependent manner. Our findings, for the first time, provide strong evidence that long-term administration of SP formula prevents the development and progression of DN in ZDF rats. Human trials are needed to confirm these experimental results.

• Korean Journal of Pharmacognosy
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• v.22 no.4
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• pp.225-232
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• 1991

The hypoglycemic and metabolic effects of Commelina communis L. extract were investigated in alloxan-diabetic rats. The increased blood glucose level in the diabetic rats was significantly lowered and the loss of body weight in the diabetic rats was recovered with the treatments of the crude extract. Administration of the extract elicited the significant increase of glucose-6-phosphate dehydrogenase activity and liver weight which were decreased in the alloxan-treated rat serum and liver. On the other hand, the kidney weight and glucose-6-phosphate dehydrogenase activity were increased in the alloxan treated rat kidney and were potentiated by the treatment of the extract. In both liver and kidney, together with serum, alkaline phosphatase and ATPase activities were increased in the alloxan diabetic rats and were not recovered, rather potentiated by the administration of the extract.