• Kidney Research and Clinical Practice
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• 제35권2호
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• pp.69-77
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• 2016

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and its pathogenesis is complex and has not yet been fully elucidated. Abnormal glucose and lipid metabolism is key to understanding the pathogenesis of DN, which can develop in both type 1 and type 2 diabetes. A hallmark of this disease is the accumulation of glucose and lipids in renal cells, resulting in oxidative and endoplasmic reticulum stress, intracellular hypoxia, and inflammation, eventually leading to glomerulosclerosis and interstitial fibrosis. There is a growing body of evidence demonstrating that dysregulation of 50 adenosine monophosphate-activated protein kinase (AMPK), an enzyme that plays a principal role in cell growth and cellular energy homeostasis, in relevant tissues is a key component of the development of metabolic syndrome and type 2 diabetes mellitus; thus, targeting this enzyme may ameliorate some pathologic features of this disease. AMPK regulates the coordination of anabolic processes, with its activation proven to improve glucose and lipid homeostasis in insulin-resistant animal models, as well as demonstrating mitochondrial biogenesis and antitumor activity. In this review, we discuss new findings regarding the role of AMPK in the pathogenesis of DN and offer suggestions for feasible clinical use and future studies of the role of AMPK activators in this disorder.

• 한국한의학연구원논문집
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• 제7권1호
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• pp.135-144
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• 2001

Objectives : This study was carried out to research the protective effects of Sagunja-Tang(SA) through in vivo experiments, and tried to investigate the relation between oxidation of renal tissues and deficiency of Qi. Methods : Acute renal injury which initiated from free radical induced by $HgCl_2$, were applied to mice and metabolic data were obtained. In order to measure the degree of renal injury, serum level of creatinine, blood urea nitrogen(BUN), total protein(TP) and glucose were measured. Besides, serum level of alanine aminotransferase(AST), aspartate aminotransferase(ALT) were measure too. Lipid peroxidation of renal cortex was examined by measuring malondialdehyde(MDA), a product of lipid peroxidation. Results : SA had protective effects on acute renal injury caused by decrease of glomerular filtration which was initiated by subcutaneous injection of $HgCl_2$. SA protected acute liver injury too. Conclusions : Through this study, we found that SA have healing effects on renal injury of $HgCl_2$ induced oxidative stress that is similar to deficiency of Qi. And further studies have to be followed to certify the mechanisms.

• 동의생리병리학회지
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• 제30권4호
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• pp.250-256
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• 2016

The prevalence of renal disease is increased with the overweight and obesity. High fat diet-associated oxidative stress increases production of reactive oxygen species (ROS) and induces apoptosis. There are two types of antioxidant defense mechanisms for oxidative stress. One is the enzyme defense mechanism by antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT). The other is non-enzyme defense mechanism by signaling molecules such as nuclear factor-like 2 (Nrf-2), HO-1. In this study, we induced obesity in mice with high fat diet for six weeks and thereafter administered orally Viola mandshurica for 4 weeks. V. mandshurica is known to clear heat, detoxify and cool blood, and subside a swelling effect. In the V. mandshurica administered group, the immunoreactive signal of the Tunel staining was weaker than that of obesity group. Proapoptotic Bax, caspase 3 immunoreactives of the V. mandshurica administered group was lower than those of obesity group, whereas anti-apoptotic Bcl-2 immunoreactity was higher in the V. mandshurica administered group. Antioxidant enzyme mechanism such as superoxide dismutase 2 (SOD2), catalase (CAT) immunoreactives of the V. mandshurica administered group and Antioxidant non-enzyme mechanism such as Nuclear factor-like 2 (Nrf2), Heme Oxygenase 1 (HO-1) immunoreactives of the V. mandshurica administered group was higher than those of obesity group. These results demonstrate that V. mandshurica had the antioxidant and anti-apoptosis effects on obese mice.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.229-236
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• 2016

Resveratrol (RSV) may provide numerous protective effects against chronic inflammatory diseases. Due to local hypoxia and hypertonicity, the renal medulla is subject to extreme oxidative stress, and aldehyde products formed during lipid peroxidation, such as 4-hydroxy-2-hexenal (HHE), might be responsible for tubular injury. This study aimed at investigating the effects of RSV on renal and its signaling mechanisms. While HHE treatment resulted in decreased expression of Sirt1, AQP2, and nuclear factor erythroid 2-related factor 2 (Nrf2), mouse cortical collecting duct cells (M1) cells treated with HHE exhibited increased activation of p38 MAPK, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and increased expression of NOX4, $p47^{phox}$, Kelch ECH associating protein 1 (Keap1) and COX2. HHE treatment also induced $NF-{\kappa}B$ activation by promoting $I{\kappa}B-{\alpha}$ degradation. Meanwhile, the observed increases in nuclear $NF-{\kappa}B$, NOX4, $p47^{phox}$, and COX2 expression were attenuated by treatment with Bay 117082, N-acetyl-l-cysteine (NAC), or RSV. Our findings indicate that RSV inhibits the expression of inflammatory proteins and the production of reactive oxygen species in M1 cells by inhibiting $NF-{\kappa}B$ activation.

• Biomolecules & Therapeutics
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• 제24권5호
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• pp.536-542
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• 2016

Shuangdan oral liquid (SDO) containing radix Salviae miltiorrhizae (Chinese name Danshen) and cortex moutan (Chinese name Mudanpi) is a traditional Chinese medicine using for treating vascular diseases. Danshensu (DSS) is a main effective monomer composition derived from radix Salviae miltiorrhizae and paeonol (Pae) from cortex moutan. Although the two herbs are widely used in traditional Chinese medicine, the pharmacological functions of their active compositions were not reported. Therefore, the research of DSS and Pae in mechanisms and pharmacodynamics interaction can provide scientific evidence to support clinical application. The diabetic nephropathy (DN) rats which were induced by streptozotocin (STZ) were treated with SDO, DSS, Pae, and DSS+Pae for eight weeks. The positive effects on DN animal models were investigated by detection of physiological and biochemical indexes and oxidative stress markers, within five treatments: SDO, DSS, Pae, DSS+Pae and insulin group. Compared with the model group, the DSS+Pae group improved the renal function, blood lipid metabolism and blood viscosity, increased the vitality of T-SOD or T-AOC and decreased the level of MDA or NO after the treatment. The study was successfully showed that the DSS+Pae group could delay the process of DN, especially in the renal injury part of histopathology changes. Our results suggest that the co-administration of DSS and Pae significantly may play a protective role in DN rats through decreasing the oxidative stress and improving the blood lipid metabolism mechanisms.

• Preventive Nutrition and Food Science
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• 제18권1호
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• pp.18-22
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• 2013

To investigate radical scavenging effects and protective activities of bitter melon (Momordica charantia) against oxidative stress, in vitro and a cellular system using LLC-$PK_1$ renal epithelial cells were used in this study. The butanol (BuOH) fraction of bitter melon scavenged 63.4% and 87.1% of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals at concentrations of 250 and $500{\mu}g/mL$, respectively. In addition, the BuOH fraction of bitter melon effectively scavenged hydroxyl radicals (${\cdot}OH$). At all concentrations tested, the scavenging activity of the BuOH fraction was more potent than that of the positive control, ascorbic acid. Furthermore, under the LLC-$PK_1$ cellular model, the cells showed a decline in viability and an increase in lipid peroxidation through oxidative stress induced by pyrogallol, a generator of superoxide anion ($O_2{^-}$). However, the BuOH fraction of bitter melon significantly and dose-dependently inhibited cytotoxicity. In addition, 3-morpholinosydnonimine (SIN-1), a generator of peroxynitrite ($ONOO^-$) formed by simultaneous releases of nitric oxide and $O_2{^-}$, caused cytotoxicity in the LLC-$PK_1$ cells while the BuOH fraction of bitter melon ameliorated oxidative damage induced by $ONOO^-$. These results indicate that BuOH fraction of bitter melon has protective activities against oxidative damage induced by free radicals.

• 대한한방내과학회지
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• 제32권2호
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• pp.278-287
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• 2011

Objectives : The object of this study was to observe the nephroprotective effects of Sojongchobisunki-tang (SCST), which has traditionally been used as Korean medicine for treating various renal diseases, on cisplatin-induced rat acute renal failure. Methods : Three different dosages of SCST were orally administered once a day for 23 days before cisplatin treatment (5 mg/kg, single intraperitoneally administered) and 5 days after cisplatin treatment (once a day for 28 days). 6 groups, of 8 rats per group were used in the present study after 7 days of acclimatization. Changes of the body weight, kidney weight, serum BUN and creatinine levels were observed, as well as changes of the kidney MDA and GSH contents. The results were compared with captopril 100 mg/kg of which the effects on cisplatin-induced acute renal failures are already confirmed. Results : Acute renal failure induced by cisplatin were induced by oxidative stress and related lipid peroxidation in the present study. However, these acute renal failures and inhibition of antioxidant effects induced by cisplatin were dose-dependently reduced by treatment at all three different dosages of SCST extracts. Conclusions : This study suggests that SCST extracts showed favorable effects on the cisplatin-induced rat ARF.

• 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.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.145.1-145.1
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• 2003

Oxidative stress has been implicated in a range of disease states, including end-stage renal failure treated with hemodialysis [Westhuyzen J. et al, 2003]. Free radicals react with biological molecules and destroy the structure of cells, which eventually causes free-radical induced disease such as cancer, renal failure, aging, etc. Exogenous or endogenously produced nitric oxide (NO) inhibits superoxide-stimulated urea permeability. In the inner medulla, superoxide generation by local oxidases may stimulate urea transport, and the role of endogenous No may be to dampen this effect by decreasing superoxide levels ［Zimpelmann J. et al, 2003 (Epub ahead of print)］. (omitted)

• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.135-143
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• 2018

Tumor necrosis $factor-{\alpha}$ ($TNF{\alpha}$) and the angiotensin system are involved in inflammatory diseases and may contribute to acute kidney injury. We investigated the mechanisms by which $TNF{\alpha}$-converting enzyme (TACE) contributes to lipopolysaccharide (LPS)-induced renal inflammation and the effect of TACE inhibitor treatment on LPS-induced cellular injury in human renal proximal tubule epithelial (HK-2) cells. Mice were treated with LPS (10 mg/kg, i.p.) and HK-2 cells were cultured with or without LPS ($10{\mu}g/ml$) in the presence or absence of a type 1 TACE inhibitor ($1{\mu}M$) or type 2 TACE inhibitor ($10{\mu}M$). LPS treatment induced increased serum creatinine, $TNF{\alpha}$, and urinary neutrophil gelatinase-associated lipocalin. Angiotensin II type 1 receptor, mitogen activated protein kinase (MAPK), and TACE increased, while angiotensin-converting enzyme-2 (ACE2) expression decreased in LPS-induced acute kidney injury and LPS-treated HK-2 cells. LPS induced reactive oxygen species and the down-regulation of ACE2, and these responses were prevented by TACE inhibitors in HK-2 cells. TACE inhibitors increased cell viability in LPS-treated HK-2 cells and attenuated oxidative stress and inflammatory cytokines. Our findings indicate that LPS activates renin angiotensin system components via the activation of TACE. Furthermore, inhibitors of TACE are potential therapeutic agents for kidney injury.