• Journal of Environmental Health Sciences
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• v.19 no.2
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• pp.78-87
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• 1993

The accumulations of mercury, lactate dehydrogenase and antioxidant enzymes activities of which are glutathione peroxidase, catalase and superoxide dismutase, and pathological changes were investigated in liver and kidney of mice which were fed the water supplemented with two levels (0.5 mM and 1.0 mM) of mercury chloride (HgCl$_2$). During the mercury feeding, the weight gain of mice in experimental groups was less than that of control group mice, while no overt signs related to mercury toxicity were noted in any experimental groups. Mercury concentrations in liver and kidney increased significantly in the early period (1~2 weeks) after mercury administration, which were measured as high as 100 times in liver and kidney in comparison to those of the control groups, but there were relatively stable for the levels of accumulation in following periods. The lactate dehydrogenase activities in liver and kidney were relatively increased in the period of 2~3 weeks of mercury administration in the experimental groups, there were normal levels in other periods of administration without the dose-dependencies. The glutathione peroxidase activities were not affected by the dosages of mercury chloride and the duration of ingestion. But the catalase activities significantly increased in 2~3 weeks after ingestion, and the superoxide dismutase activities of kidney also showed a peak in 3 weeks of ingestion while this peak was not found in the results measured in liver tissues.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.3
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• pp.221-230
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• 2023

Diabetic kidney disease is one of the most serious complications of diabetes. Although diabetic kidney disease can be effectively controlled through strict blood glucose management and corresponding symptomatic treatment, these therapies cannot reduce its incidence in diabetic patients. The sodium-glucose cotransporter 2 (SGLT2) inhibitors and the traditional Chinese herb "Gegen" have been widely used in diabetes-related therapy. However, it remains unclear whether the combined use of these two kinds of medicines contributes to an increased curative effect on diabetic kidney disease. In this study, we examined this issue by evaluating the efficacy of the combination of puerarin, an active ingredient of Gegen, and canagliflozin, an SGLT2 inhibitor for a 12-week intervention using a mouse model of diabetes. The results indicated that the combination of puerarin and canagliflozin was superior to canagliflozin alone in improving the metabolic and renal function parameters of diabetic mice. Our findings suggested that the renoprotective effect of combined puerarin and canagliflozin in diabetic mice was achieved by reducing renal lipid accumulation. This study provides a new strategy for the clinical prevention and treatment of diabetic kidney disease. The puerarin and SGLT2 inhibitor combination therapy at the initial stage of diabetes may effectively delay the occurrence of diabetic kidney injury, and significantly alleviate the burden of renal lipotoxicity.

• Molecular & Cellular Toxicology
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• v.3 no.2
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• pp.113-118
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• 2007

Chlorobenzenes due to their acute toxicity and the capability of bioaccumulating are of great health and environmental concern. Especially, 1, 2-dichlorobenzene (CAS No. 95-50-1) is used for organic synthesis, dye manufacture, as a solvent and for other applications in chemical industry. Adverse effects of 1, 2-dichlorobenzene includes increases in liver and kidney weights and hepatotoxicity. In this study, we evaluated the genetic toxicity of 1, 2-dichlorobenzene with more advanced methods, in vitro mouse lymphoma assay $tk^{+/-}$ gene assay (MLA) and in vitro mouse supravital micronucleus (MN) assay. 1, 2-Dichlorobenzene appeared the significantly positive results and the induction of large mutant colonies only in the presence of metabolic activation system with MLA. But in vitro testing of 1, 2-dichlorobenzene yielded negative results with supravital MN assay. These results suggest that 1, 2-dichlorobenzene may play a mutagen rather than clastogen in vitro mammalian system.

• Applied Microscopy
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• v.30 no.4
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• pp.389-401
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• 2000

The mouse for identifying the histological changes of kidney were also divided into the two groups; treated with only $HgCl_2$ (4 mg/kg), the group treated with $HgCl_2$ and squalene (200 mg/kg). The $HgCl_2$ treated only one time at first day. The squalene treated two times a day (12 hours interval) for every day. Each groups were divided into the five groups; 6, 12, 24, 48 and 72 hours after treated $HgCl_2$ and squalene. Historical changes of the kidneys were investigated by electron microscope. The group with only $HgCl_2$ showed that the nuclear membrane was shrinked, the inner membrane (cristae) of the mitochondria were destructed, and ribosomes on the rough endoplasmic reticulum were lost. The group treated with $HgCl_2$ and Squalene showed that the nuclear membrane was more rounded, the cristae of the mitochondria were almost normal shape, and more ribosomes on the rough endoplasmic reticulum were attached. Therefore , we concluded that squalene has significantly protective effects in kidney to harmful $HgCl_2$.

• Applied Microscopy
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• v.36 no.2
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• pp.57-72
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• 2006

A protective effect of activated charcoal against the acute lead poisoning of kidney was studied in mice. Mice approximately 30 gm in weight were grouped into the control, lead acetate-treated. and the activated charcoal-treated after lead acetate groups. Lead acetate (60mg/kg) and activated charcoal (40mg/kg) were delivered orally. Serum BUN and creatine were measured and ultrastructural alteration of renal tissues were examined by electron microscopy. Activated charcoal were decreased the increase of serum BUN and Creatinine level induced by lead. Lead acetate-treated renal tissues were characterized by the loss of microvilli in the renal tubule tells, irregular nucleus, enlarged and reduced number of mitochodria, enlarged rough endoplasmic reticulum, loss of ribosomes. Cells treated with activated charcoal were similar to those of the control group. In conclusion, activated charcoal may protect the lead-induced toxicity on kidney.

• BMB Reports
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• v.52 no.9
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• pp.554-559
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• 2019

Despite reports suggesting that tissue-resident natural killer (trNK) cells cause ischemic kidney injury, their contribution to the development of tubulointerstitial fibrosis has not been determined. This study hypothesized that the depletion of trNK cells may ameliorate renal fibrosis by affecting transglutaminase 2/syndecan-4 interactions. Aristolochic acid nephropathy (AAN) was induced in C57BL/6 mice as an experimental model of kidney fibrosis. The mice were treated with anti-asialo GM1 (ASGM1) or anti-NK1.1 antibodies to deplete NK cells. Although both ASGM1 and NK1.1 antibodies suppressed renal $NKp46^+DX5^+$ NK cells, renal $NKp46^+DX5^-$ cells were resistant to suppression by ASGM1 or NK1.1 antibodies during the development of tubulointerstitial fibrosis in the AAN-induced mouse model. Western blot analysis showed that both antibodies increased the expression of fibronectin, transglutaminase 2, and syndecan-4. These findings indicate that trNK cells played an exacerbating role in tubulointerstitial fibrosis by activating transglutaminase 2 and syndecan-4 in the AAN-induced mouse model.

• The Journal of Korean Medicine
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• v.28 no.3 s.71
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• pp.57-69
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• 2007

Objectives : Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications have shown that oxidative stress might play a major role. Therefore, many methods have been tried to regulate free oxygen radicals for treating diabetes and its complications. Ojung-hwan, composed of five crude herbs, has been considered effective for treating symptoms of aging. In male ob/ob mouse of severe obesity, hyperinsulinemia and hyperlipidemia, which are features of NIDDM, the hyperglycemic activities and mechanisms of Ojung-hwan were examined. Methods : Mice were grouped and treated for 5 weeks as follows. Both the lean (C57/BL6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed a diet of chow supplemented with 30 and 90 mg Ojung-hwan per 1 kg of body weight for 14 days. The effects of Ojung-hwan extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of superoxide anion radical (${\cdot}\;O{_2}{^-}$), MDA+HAE, GSH/GSSG ratio, and also the enzyme activities involved in polyol pathway. Results : Ojung-hwan lowered the levels of serum glucose and insulin in a dose-dependent manner. Total cholesterol, triglyceride and free fatty acid levels decreased, while the HDL-cholesterol level increased, in Ojung-hwan treated groups. Renal aldose reductase and sorbitol dehydrogenase activities increased in the ob/ob mice, whereas they were inhibited in the Ojung-hwan treated groups. Ojung-hwan inhibited the generation of ${\cdot}\;O{_2}{^-}$ in the kidney. Finally, MDA+HAE levels increased and GSH/GSSG ratio decreased in the ob/ob mice, whereas they improved in the Ojung-hwan treated groups. Conclusions : Ojung-hwan showed antidiabetic and antihyperlipidemic activities by regulating theactivities of polyol pathway enzymes, scavenging reactive oxygen species and reducing the MDA+HAE levels in the ob/ob mice.

• Journal of Pharmacopuncture
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• v.12 no.3
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• pp.25-30
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• 2009

Objectives: To find the potential acupuncture points by using Trypan blue staining on the skin of rat and Nude mouse. Methods: 0.4% Trypan blue was applied to the skin of rat or Nude mouse previously treated by surfactant. Washing by warm saline was followed after enough application of trypan blue and surfactant. Frequency of Trypan blue application should be varied to the experimental animals' condition for visualizing significant spots. Results: Blue spots appeared roughly in symmetry along kidney meridian or stomach meridian. Several spots outside of kidney or stomach meridian were also observed; however, the detail stereoscopic images of those blue spots were slightly different according to the position blue-colored. DiI signals were visualized along blood vessel after DiI injection into the Trypan blue-visualized blue spots. Conclusion: Our method to visualize the potential acupuncture points as a blue spot on rat and Nude mouse skins may contribute to the next step for finding specific flowing channels among blue spots.

• Preventive Nutrition and Food Science
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• v.21 no.4
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• pp.378-383
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• 2016

Diabetic kidney disease is the most common and severe chronic complication of diabetes. The leaf of Diospyros kaki Thumb (persimmon) has been commonly used for herbal tea and medicinal purposes to treat a variety of conditions, including hypertension and atherosclerosis. However, the effect of persimmon leaf on kidney failure has not been investigated. This study aimed to examine the role of persimmon leaf in protecting the diabetes-associated kidney damage in a mouse model of type 2 diabetes. Mice were fed either a normal chow diet with or without powered persimmon leaf (5%, w/w) for 5 weeks. In addition to kidney morphology and blood markers of kidney function, we assessed levels of oxidative stress markers as well as antioxidant enzymes activities and mRNA expression in the kidney. Supplementation of the diet with powered persimmon leaf not only decreased the concentration of blood urea nitrogen in the plasma but also improved glomerular hypertrophy. Furthermore, the persimmon leaf significantly decreased the levels of hydrogen peroxide and lipid peroxide in the kidney. The activities of superoxide dismutase, catalase, and glutathione peroxidase and the mRNA expression of their respective genes were also increased in the kidney of persimmon leaf-supplemented db/db mice. Taken together, these results suggest that supplementation with the persimmon leaf may have protective effects against type 2 diabetes-induced kidney dysfunction and oxidative stress.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.3
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• pp.127-137
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• 2015

Purpose: The main aim of this study was to compare and analyze expression profiles of microRNAs (miRNAs) to establish miRNA signature of Fabry nephropathy related epithelial mesenchymal transition (EMT). Methods: Expression profiles of miRNAs in kidney tissue samples and cell lines from normal and Fabry disease mouse model were examined by miRNA expression microarray analysis followed by quantitative real-time polymerase chain reaction analysis (qRT-PCR). Results: In the miRNA expression microarray analysis of Fabry mouse kidney tissues compared to wild type mouse, 5 and 3 miRNAs among 1,247 miRNAs examined were up- and down-regulated, respectively. Among them, miR-149-5p was down-regulated about 2-fold in Fabry kidney samples. The down-regulations of miR-149-5p were observed in kidney tissues of under 35 week-old-Fabry mice. However, this down-regulation was not observed in kidney tissues of 42 week-old Fabry mice. In SV40 MES 13 cells, mouse mesangial cells, treated with globotriaosylsphingosine (lyso-Gb3), miR-149-5p was also downregulated. The down-regulation of miR-149-5p induced up-regulation of its target genes related to EMT. Conclusion: The miRNA expression array and qRT-PCR results show that miR-149-5p expression was decreased in kidney tissues of Fabry mice compared to wild type mice under 35 weeks of age. Along with the observation of miR-149-5p expression in Fabry disease cell models, these results indicate that the down-regulated miR-149-5p were related to the biological response of mesangial cells to lyso-Gb3 and also have influence to the transcriptional up-regulation of its target genes. These results suggest miR-149-5p might play important roles in the Fabry nephropathy.