• Journal of Veterinary Clinics
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• v.36 no.3
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• pp.145-149
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• 2019

Previous report has suggested that the albumin levels were reduced in the peripheral blood mononuclear cells (PBMCs) and consequently oxidative stress was elevated in streptozotocin (STZ)-induced diabetic rats as albumin is the predominant antioxidant in plasma. In this study, we suggest that the levels of pro-inflammatory cytokine such as interleukin-6 (IL-6) and tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$) were increased by approximately 3.4- and 2.9-fold, respectively, in the serum of STZ-diabetic rats, compared to those of normal rat. In addition to the cytokines, the levels of C-reactive protein (CRP) were also about 3.6-fold higher, indicating that STZ induced a pro-inflammatory response in rat blood. However, when purified rat albumin was externally co-administrated with STZ through the tail vein, the serum levels of IL-6, $TNF-{\alpha}$, and CRP were markedly reduced, although the values were still higher than those of normal (non-diabetic) rats. Albumin administration also decreased STZ-induced oxidative stress in serum and PBMCs. Moreover, the decrease in cytokine and CRP levels was dependent on the dose of injected albumin. These results suggest that STZ-induced pro-inflammation and oxidative stress in rat blood might be attenuated by treatment with exogenous albumin.

• YAKHAK HOEJI
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• v.36 no.1
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• pp.80-86
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• 1992

Streptozotocin (STZ) is a naturally occurring nitrosoamide used extensively to produce diabetes in experimental animals. Our previous study has demonstrated that i.v. administraton of streptozotocin induces significant red blood cell hemolmysis in rats. Since it has been reported that the highest concentration of STZ is found in the liver, the effect of STZ in freshly isolated rat hepatocytes has been investigated. STZ treatment (10 mM) did not cause significant loss of viability throughout 4 hour incubation, while high dose of STZ (300 mM) to hepatocytes resulted in complete cell death within 3 hours. Addition of 40 mM glucose to incubation medium did not potentiate STZ-induced hepatotoxicity, suggesting that STZ-induced hyperglycemia in vivo did not affect its hepatotoxicity. To investigate the mechanixm of the toxicity, intracellular total glutathione level was determined. Tratment with 10 mM STZ which was not toxic to hepatocytes led to complete depletion of intracellular glutathione level within 1 hour incubation. These results suggest that STZ-induced hepatotoxicity may be independent on the intracellular glutathione depletion.

• The Journal of Korean Medicine
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• v.27 no.1 s.65
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• pp.47-56
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• 2006

The present study was carried out to investigate the preventive effect of Epimedii Herba combined Samgijiwhang-Tang(SJTE) on streptozotocin(STZ)-induced diabetic nephropathy. SJTE was given to rats with oral administration. The experimental animals were divided into normal group of rats, control group of STZ-induced diabetic rats, and sample group with SJTE administration. Experimental diabetic nephropathy was induced by the injection of STZ(60mg/kg) to the rat via the peritoneum. The effect of SJTE on STZ-induced diabetic nephropathy was observed by measuring the serum level of insulin, glucose, creatinine and BUN. Urine secretion of albumin for 24 hours and urine level of glucose measures too. Anti-oxidative stress of STZ administration in living body was estimated by measuring lipid peroxide in cortex of kidneys. STZ induced increase of serum glucose. creatinine, urine albumin secretion and renal cortical lipid peroxidation were lowered by SJTE administration. In conclusion, the SJTE treatment showed protective effect on rat diabolic nephropathy model, and action mechanism of the effect was thought to be concerned with internal glucose metabolism.

• The Korea Journal of Herbology
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• v.21 no.3
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• pp.75-81
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• 2006

Objectives : The present study was carried out to investigate the beneficial effect of Coicis Semen extract(CSe) on streptozotocin(STZ)-induced diabetic nephropathy rats. CSe was given to rats with oral administration. Methods : The experimental animals were divided into 3 groups : normal group of rats, control group of STZ-induced diabetic rats, sample group with CSe treatment. Experimental diabetes was induced by the injection of STZ(60 mg/kg) to the rat via the peritoneum. The effects of CSe on STZ-induced diabetic nephropathy were observed by measuring the serum level of creatinine, BUN and uric level of glucose. Kidney level of lipid peroxidation and the activities of reduced glutathione(GSH) were also examined Results : STZ-induced increase of serum creatinine was lowered by CSe treatment, but BUN and uric level of glucose did not show significant changes. CSe oral administration showed statistical decrease of lipid peroxidation in renal cortical tissues, but it has no effect on the activities of GSH. Conclusion : CSe treatment showed protective effect on rat diabetic nephropathy model, but action mechanism of the effect was still not dear. We thought to be concerned with anti-oxidative stress.

• Korean Journal of Veterinary Research
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• v.40 no.3
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• pp.489-496
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• 2000

This study was conducted to investigate the effects of streptozotocin-induced (STZ) diabetes on insulin-like growth factor-I (IGF-I), insulin-like growth factor binding proteins (IGFBPs), and IGF-I carrier proteins in serum, liver, and kidney. The levels of total and free IGF-I were measured by radioimmunoassay (RIA). The patterns of IGFBPs were determined by western ligand blotting (WLB) analysis. The profiles of IGF-I carrier proteins in serum were determined by column chromatography. The levels of total and free IGF-I in serum were lower in STZ-induced diabetic rat than normal rat (p<0.01). Similarly, the levels of total IGF-I in liver was lowered in STZ-induced diabetic rats. On the other hand, the levels of total IGF-I in kidney were increased in STZ-induced diabetic rats compared with normal rats (p<0.01). In serum and liver from STZ-induced diabetic rats, the amount of IGFBP-3 was decreased and the amount of IGFBP-2 was increased compared with normal rats. There was a not difference in amount of IGFBP-4 in serum between STZ-induced diabetic rats and normal rats. The serums of normal rats have higher 150kDa carrier proteins than in STZ-induced diabetic rats, whereas, most of 50kDa carrier proteins were found in STZ-induced diabetic rats. These results demonstrate that in STZ-induced diabetic rats, IGF-I/IGFBPs system that included functional bioactivity was changed in serum as well as tissues, and these changes may play an important role in pathogenesis of diabetes.

• The Journal of Korean Medicine
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• v.27 no.3 s.67
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• pp.77-87
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• 2006

Objectives: The present study was carried out to investigate the preventive effects of Samgijiwhang-Tang(SJT) on streptozotocin(STZ)-induced diabetic nephropathy. Methods: SIT was given to rats through oral administration. The experimental animals were divided into a normal group of rats, a control group of STZ-induced diabetic rats, and a sample group with SIT administration. Rehmanniae Radix Preparat is combined in the original prescription of SIT, but in this experiment, Rehmanniae Radix was combined instead of Rehmanniae Radix Preparat to compare the effects of anti-diabetic nephropathy. Experimental diabetic nephropathy was induced by the injection of STZ(60mg/kg) in the rat via the peritoneum. The effect of SIT on STZ-induced diabetic nephropathy was observed by measuring the serum level of creatinine and BUN, in addition to urine secretion of albumin for 24 hours and the level of glucose found in the urine. Anti-oxidative stress of SIT administration in a living body was estimated by measuring lipid peroxide and GSH content in the cortex of kidneys. Results: STZ induced an increase of serum creatinine, urine glucose and renal cortical lipid peroxidation was lowered by Rehmanniae Radix Preparat combined SIT administration. Conclusions: The SIT treatment showed a protective effect on the rat diabetic nephropathy model, and action mechanism of the effect was thought to be concerned with anti-oxidative stress.

• Advances in Traditional Medicine
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• v.8 no.2
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• pp.146-153
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• 2008

The present study is aimed at finding the influence of silymarin (a flavonoid) (25 mg/kg & 50 mg/kg) in streptozotocin (STZ)-induced diabetic rats. Type 2 diabetes was induced by single intraperitoneal injection of STZ (100 mg/kg) to 3 days old rat pups. Silymarin was administered for 15 days after the animals were confirmed diabetic (75 days after STZ injection). Blood glucose, glycosylated hemoglobin ($HbA_{1c}$), lipid peroxides (LPO) levels and reduced glutathione (GSH) contents in pancreas and liver were estimated following the established procedures. Biochemical observations were further substantiated with histological examination of pancreas. Blood glucose and $HbA_{1c}$ levels, which were elevated by STZ, were lowered to physiological levels by the administration of silymarin. The levels of LPO were significantly increased in STZ-induced diabetic rats. Silymarin reduced the LPO levels in both pancreas and liver. GSH contents which were reduced significantly in pancreas and liver of STZ-induced diabetic rats were brought back to near normal levels by silymarin treatment. Multifocal necrotic and degenerative changes of pancreas in STZ-diabetic rats were minimized to near normal morphology by administration of silymarin as evident by histopathological examination. Silymarin showed a dose dependent protective effect on STZ-induced $\beta$-cell damage. It could be attributed to the antioxidative and free radicals scavenging properties of the flavonoid. Thus, it may be considered as a natural antioxidant with potential therapeutic application in the treatment of type 2 diabetes.

• Journal of Acupuncture Research
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• v.26 no.6
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• pp.1-9
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• 2009

Objectives : For evaluation of preventive and anti-diabetic activities of Cinnamomi ramulus(CR) herbal acupuncture on pancreatic islet damage in streptozotocin(STZ)-induced diabetic rat. Methods : CR herbal acupuncture was performed at Bisu($BL_{20}$) for 3 weeks subcutaneously starting1 week before STZ i.p. injection. SD rats were divided into four groups(n=10 for each group); 1) NC group, non-treated normal control group, 2) STZ group, STZ administered control group, 3) CR125 group, CR(125mg/kg) + STZ administered group, and 4) CR250 group, CR(250mg/kg) + STZ administered group. Results : Both of CR250 and CR125 groups showed increase in insulin secretion and decrease in the level of serum triglyceride and non-esterified fatty acid in a dose-dependent manner compared to the STZ group. Only CR250 group showed decrease in the levels of glucose and total cholesterol compared to the STZ group. CR herbal acupuncture prevents $\beta$-cell damage of pancreatic islet, showing round figure on the sections of the pancreas. In the pancreatic cells, expressions of iNOS, JNK-2, P-JNK-1/2 and ERK-1/2 were decreased compared to the STZ group. CR herbal acupuncture solution did not show any cytotoxicity by MTS assay and inhibited expressions of iNOS and COX-2 in the STZ-induced diabetic rats. Conclusions : Therefore, we suggest that CR herbal acupuncture may act as a prophylactic as well as a therapeutic modality for diabetes mellitus.

• The Journal of Internal Korean Medicine
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• v.30 no.4
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• pp.858-879
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• 2009

Objectives : The object of this study was to investigate the effects of Daeboeum-hwan (DBEH) aqueous extracts on Streptozotocin (STZ)-induced rat diabetes and related complications. Methods : SD rats were divided into 6 groups (n =8) : 50 mM citrate buffer and vehicle (distilled water 5 ml/kg) administered group (Intact control), STZ treatment (60 mg/kg, single intraperitoneally administered) and vehicle administered group (STZ control), STZ treatment and silymarin 100 mg/kg administered group (Reference), and STZ treatment and DBEH extracts 50, 100 and 200 mg/kg administered groups. DBEH extracts were orally administered once a day for 28 days from 3 weeks after STZ treatment. The results were compared with silymarin 100 mg/kg. Results : Decreases in the body weights, increase of kidney and liver weights, blood glucose, BUN, creatinine, AST, ALT, LDL, triglyceride and total cholesterol levels with decreases of HD L levels, increases of pancreatic MDA contents and decreases of GSH contents were detected in STZ control as compared with intact control. These diabetes and related complications were inhibited by treatment with 100 and 200 mg/kg of DBEH extracts. Conclusion : DBEH extracts showed favorable effects on STZ-induced diabetes and related complications mediated by their antioxidant effects as similar to silymarin. Because the lowest dosage (50 mg/kg) of DBEH treated group did not show any favorable effects as compared with STZ control, the effective dosages of DBEH is considered as about 100 mg/kg, while DBEH extracts at 200 mg/kg showed similar effects as compared with 100 mg/kg of silymarin. It, therefore, is expected that DBEH will show favorable effects on diabetes and various diabetic complications.

• Journal of Acupuncture Research
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• v.22 no.5
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• pp.1-10
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• 2005

Objectives : The Present study was carried out to investigate the preventive effect of Anti-diabetic prescription 1(AD-1) on streptozotocin(STZ)-induced diabetic nephropathy. Methods : AD-1 consists of eleven herbs that have an effect on diabetes mellitus. AD-1 was given to rats with the combination of oral administration and herbal-acupuncture stimulation. The experimental animals were divided into 3 groups : normal group of rats, control group of STZ-induced diabetic rats, sample group with AD-1 treatment. Experimental diabetes was induced by the injection of STZ(60mg/kg) to e rat via the peritoneum. The effect of AD-1 on STZ-induced diabetic nephropathy was observed by measuring the serum level of creatinine and BUN. Urine secretion of albumin for 24 hours and urine level of glucose measures too. Anti-oxidative stress of AD-1 administration in living body was estimated by measuring lipid peroxide and GSH content in cortex of kidneys. Results : STZ induced increase of serum creatinine, BUN and albumin secretion were lowered by AD-1 treatment. Conclusion : The AD-1 treatment showed protective effect on rat diabetic nephropathy model, and action mechanism of the effect was thought to be concerned with anti-oxidative stress.