• 대한본초학회지
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• 제33권4호
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• pp.1-7
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• 2018

Objectives : Diabetic nephropathy is one of the most significant chronic complications of diabetes. Advanced glycation end products (AGEs) have been implicated in the development of diabetic nephropathy. GS-E3D is an enzymatic modified red ginseng extract by pectin lyase and has an increased concentration of the ginsenoside Rd compared to an unmodified red ginseng extract. In this study, we evaluated the preventive effects of GS-E3D on renal dysfunction in the type 2 diabetic db/db mice. Methods : GS-E3D (100 or 250 mg/kg body weight per day) was given to db/db mice through oral gavage for 6 weeks. Body weight and blood glucose levels were examined. At the end of the experiment, albuminuria was measured. The renal tissues were collected for histological examination, and immunohistochemical staining was used to detect renal accumulation of AGEs and podocyte loss Results : In the db/db mice, severe hyperglycemia developed, and albuminuria was significantly increased. Diabetes induced markedly morphological alterations to the renal glomerular cells. AGE accumulations and podocyte loss were detected in renal glomeruli. No difference in blood glucose levels was noted between GS-E3D-treated and vehicletreated diabetic db/db mice. However, GS-E3D treatment significantly reduced albuminuria and AGE accumulations in diabetic mice. Moreover, the loss of podocytes was restored by GS-E3D treatment. Conclusions : GS-E3D might be beneficial for the treatment of diabetic nephropathy. The ability of GS-E3D on to attenuate albuminuria and podocyte dysfunction in the db/db mice may be mediated by the inhibition of AGE accumulation.

• Korea-Australia Rheology Journal
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• 제17권3호
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• pp.117-123
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• 2005

Background: Reduced deformability of red blood cells (RBCs) may play an important role on the pathogenesis of chronic vascular complications of diabetes mellitus. However, available techniques for measuring RBC deformability often require washing process after each measurement, which is not optimal for day­to-day clinical use at point of care. The objectives of the present study are to develop a device and to delineate the correlation of impaired RBC deformability with diabetic nephropathy. Methods: We developed a disposable ektacytometry to measure RBC deformability, which adopted a laser diffraction technique and slit rheometry. The essential features of this design are its simplicity (ease of operation and no moving parts) and a disposable element which is in contact with the blood sample. We studied adult diabetic patients divided into three groups according to diabetic complications. Group I comprised 57 diabetic patients with normal renal function. Group II comprised 26 diabetic patients with chronic renal failure (CRF). Group III consisted of 30 diabetic subjects with end-stage renal disease (ESRD) on hemo-dialysis. According to the renal function for the diabetic groups, matched non-diabetic groups were served as control. Results: We found substantially impaired red blood cell deformability in those with normal renal function (group I) compared to non-diabetic control (P = 0.0005). As renal function decreases, an increased impairment in RBC deformability was found. Diabetic patients with chronic renal failure (group II) when compared to non-diabetic controls (CRF) had an apparently greater impairment in RBC deformability (P = 0.07). The non-diabetic cohort (CRF), on the other hand, manifested significant impairment in red blood cell deformability compared to healthy: control (P = 0.0001). Conclusions: The newly developed slit ektacytometer can measure the RBC deformability with ease and accuracy. In addition, progressive impairment in cell deformability is associated with renal function loss in all patients regardless of the presence or absence of diabetes. In diabetic patients, early impairment in RBC deformability appears in patients with normal renal function.

• Biomolecules & Therapeutics
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• 제29권4호
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• pp.365-372
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• 2021

Type 2 diabetes mellitus (T2DM) leads to many health problems like diabetic nephropathy (DN). One of the key factors for chronic kidney disease and end-stage renal disease (ESRD) is T2DM. Extensive work is being done to delineate the pathogenesis of DN and to extend possible remedies. This review is intended to understand the nature of DN risk factors, progression, effects of glycemic levels, and stages of DN. We also explored the novel diagnostic and therapeutic approaches for DN such as gene therapy and stem cell treatments.

• 대한약리학회지
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• 제31권1호
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• pp.95-102
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• 1995

당뇨병성 신증은 만성 당뇨병에서 흔히 동반되는 심각한 합병증이나 그 발생기전은 확실히 밝혀져 있지 않다. 본 연구에서는 암, 노화, 염증등 여러 가지 질환의 발생에 관여한다고 알려진 산화성 스트레스의 증가가 당뇨병성 신증의 발생에 관여하는지를 알아 보았다. 쥐에서 신증의 유발을 용이하게 하기 위해 먼저 한쪽 신장을 적출한후 스트렙토조토신을 주사하여 당뇨병을 유발하였다(NEPH-STZ). 당뇨병 유발 8주후, NEPH-STZ쥐들은 심한 고혈당증, 단백뇨, 고혈압의 증상을 보였으며 신장조직은 보상성 비대와 함께 혈관간기질(mesangial matrix) 증대의 형태학적 변화를 보였다. 그러나 스트렙토조토신만을 주사한 쥐(STZ)에서는 단백뇨가 나타나지 않았고, 신장적출만을 한 쥐에서는(NEPH) 단백뇨의 증상은 나타났으나 신장조직의 형태학적 관찰에서 혈관간 기질의 증대는 보이지 않았다. 이화같이 그 증상이나 신장조직 병변의 정도는 모두 달랐음에도 불구하고, 신피질 조직 단백질의 산화는 NEPH, STZ, NEPH-STZ의 세 실험군 쥐에서 대조군(CONT)에 비해 유의하게 증가 되어 있었다. 이 실험결과는 세 실험군 모두에서 조직의 산화성 스트레스가 증가되어 있음을 나타내는 것으로, 산화성 스트레스의 증가가 당뇨병성 신증을 일으키는 유일한 발병기전은 아닐 가능성을 시사한다. 그러나 조직의 산화성 스트레스의 증가가 여러 질환에서 조직의 손상을 유발하는 공통된 최종 경로라는 것을 고려해 볼 때, 혈행학적(hemodynamic) 혹은 대사성 인자 등에 의해 증가된 산화성 스트레스가 당뇨병성 신증의 발생에 있어서도 기여할 가능성은 크다.id deptide의 양이 변해서가 아니라 다른 기전에 의하여 조절되어지고 있음을 시사한다.

• Molecules and Cells
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• 제38권4호
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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.

• 대한한의학방제학회지
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• 제21권1호
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• pp.154-160
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• 2013

Objectives : To investigate the therapeutic effect and underlying mechanisms of rhein on renal fibrosis in diabetic rats. Methods : Diabetic nephropathy (DN) was induced in adult Wistar rats via introperitoneal injection of streptozotocin (STZ) (20 mg/kg/d) for three consecutive days. Two days after the last dose of STZ, rhein was administered to the diabetic rats at a dose of 25 mg/kg or 50 mg/kg, twice a day by gavage, respectively. Following 28 days treatment with rhein, the plasma glucose and creatinine levels were measured, the renal levels of TGF-${\beta}1$ protein and mRNA were examined, and the fibronectin mRNA levels were also determined. Results : Rhein significantly inhibited the increased plasma glucose and creatinine levels of diabetic rats in a dose- and a time-dependent way. Immunohistochemical analysis showed both doses of rhein markedly attenuated elevated induction of renal TGF-${\beta}1$ protein expressions in diabetic rats. Additionally, the high dose of rhein improved both TGF-${\beta}1$ and fibronectin mRNA expressions, while the low dose of rhein only alleviated fibronectin mRNA expressions. Conclusions : Rhein can improve renal fibrosis in diabetic nephropathy rats, and which may be mediated through inhibition of the renal mRNA expressions of TGF-${\beta}1$ and fibronectin.

• 동의생리병리학회지
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• 제18권4호
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• pp.1207-1212
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• 2004

Twenty-one diabetic nephropathy patients with normal serum BUN(Blood Urea Nitrogen), creatinine levels and ten chronic renal failure patients with abnormal high BUN, creatinine levels were investigated to evaluate the renal function change after long term herb medicine administration. The hospitalized patients were administrated three times a day with herb medicine, which were prescribe frequently in practical oriental medicine such as many hospital and local clinics. Blood Urea Nitrogen, creatinine and glomerular filtration rate (GFR) were measured immediately after 7days medication. Serum BUN, creatinine levels in diabetic nephropathy patients changed from 17.63±4.38㎎/㎗, 1.09±0.26㎎/㎗(mean±SD) of pre-medication levels to 14.13±3.24 1,20±0.37, 14.75±2.21 1.23±0.55, 12.34±2.89 1.18±0.42 at 7th, 14th, 21th days after herb medicine administration respectively. Also 24hr urine total protein changed from 632.25±254.43㎎/㎗ of pre-medication levels to 623.18±231.56㎎/㎗ after herb medicine administration(P>0.05). Serum BUN, creatinine levels and GFR in chronic renal failure patients changed from 67.45±13.86㎎/㎗, 6.74±2.91㎎/㎗, 13.73±4.21㎖/min pre-medication levels to 61.23±17.75 6.43±2.29 15.49±3.56, 58.84±19.36 5.83±2.51 16.38±2.85, 56.39±20.33 5.64±2.52 16.73±3.40 at 7th, 14th, 21th days after herb medicine administration respectively. Therefore, there was not clinically remarkable difference in the serum BUN, creatinine, GFR levels between pre-medication and post-medication in both Group.

• BMB Reports
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• 제38권5호
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• pp.539-544
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• 2005

We have studied the effects of red wine on brain oxidative stress and nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Wistar rats with a single intraperitonally injection of STZ (50 mg/kg). Two weeks before and four weeks after injection, red wine was given orally in both normal and diabetic rats. Blood samples were taken from the neck vascular trunk in order to determine the glucose, triglycerides, total cholesterol, HDL-cholesterol (HDL-c), atherogenic index (AI), total protein, blood urea nitrogen (BUN), creatinine, insulin, lipid peroxidation products, reduced glutathione (GSH) and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. As well, we estimated the lipid peroxidtion, GSH and SOD, GSH-Px and catalase activities in brain and renal homogenates, and the excretion of albumin, proteins and glucose in urine over 24 h period. The administration of STZ caused significant increases in levels of glycosuria, proteinuria, albuminuria, glycemia, total cholesterol and AI, as well as in lipid peroxidation products in the brain, plasma and kidney, whereas it decreased the GSH content and SOD, GSH-Px and catalase activities. Treatment with red wine significantly prevented the changes induced by STZ. These data suggested that red wine has a protective effect against brain oxidative stress, diabetic nephropathy and diabetes induced by STZ, as well as it protects against hypercholesterolemia and atherogenic risk.

• The Korean Journal of Physiology and Pharmacology
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• 제24권5호
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• pp.403-412
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• 2020

Diabetic nephropathy (DN) is a hyperglycemia-induced progressive development of renal insufficiency. Excessive glucose can increase mitochondrial reactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction. Our previous study indicated that cilostazol (CTZ) can reduce ROS levels and decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes. This study investigated the potential mechanisms of CTZ in rats with DN and in high glucose-treated mesangial cells. Male Sprague-Dawley rats were fed 5 mg/kg/day of CTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealed that CTZ reduced the thickness of the glomerular basement membrane and improved mitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatment reduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemia and interacted with the intrinsic pathway for regulating cell apoptosis as an antiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROS production, altered the apoptotic status, and down-regulated transforming growth factor beta (TGF-β) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). Base on the results of our previous and current studies, CTZ deceleration of hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenance of the mitochondrial function and reduction in TGF-β and NF-κB levels.

• 대한중풍순환신경학회지
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• 제18권1호
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• pp.13-22
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• 2017

■ Objectives This case is to report the effect of Oryeong-san and acupuncture therapy on serum creatinine level of a cerebral infarction patient with diabetic nephropathy. ■ Methods A female Korean patient was treated with Oryeong-san, acupuncture for total 32 days. We observed renal function test, input/output balance, body weight, hand and foot circumferences, and other symptoms like edema, urination, and any adverse event. ■ Results After treatment, serum creatinine level was improved to 2.48mg/dL from 3.45mg/dL at admission, and foot circumference was decreased to 18.5~18.9cm from 22.0~22.5cm without any adverse event. However, we couldn't find any significant differences on input/output balance, body weight, or symptoms of urination. ■ Conclusion This case suggests that Oryeong-san and acupuncture therapy could be effective in improving serum creatinine clearance of cerebral infarction patient with diabetic nephropathy.