• Journal of Preventive Medicine and Public Health
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• 제39권3호
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• pp.199-204
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• 2006

Objectives: Mercury is a hazardous organ-specific environmental contaminant. It exists in a wide variety of physical and chemical states, each of which has unique characteristics for the target organ specificity. Exposure to mercury vapor and to organic mercury compounds specifically affects the CNS, while the kidney is the target organ for inorganic Hg compounds. Methods: In this study, mercury chloride $(HgCl_2)$ was studied in a renal derived cell system, i.e., the tubular epithelial Madin-Darby canine kidney (MDCK) cell line, which has specific sensitivity to the toxic effect of mercury. MDCK cells were cultured for 6-24 hr in vitro in various concentrations (0.1-100 M) of $HgCl_2$, and the markers of apoptosis or cell death were assayed, including DNA fragmentation, caspase-3 activity andwestern blotting of cytochrome c. The influence of the metal on cell proliferation and viability were evaluated by the conventional MTT test. Results: The cell viability was decreased in a time and concentration dependent fashion: decreases were noted at 6, 12 and 24 hr after $HgCl_2$, exposure. The increases of DNA fragmentation were also observed in the concentrations from 0.1 to 10 M of $HgCl_2$ at 6 hr after exposure. However, we could not observe DNA fragmentation in the concentrations more than 25 M because the cells rapidly proceeded to necrotic cell death. The activation of caspase-3 was also observed at 6 hr exposure in the $HgCl_2$ concentrations from 0.1 to 10 M. The release of cytochrome c from the mitochondria into the cytosol, which is an initiator of the activation of the caspase cascade, was also observed in the $HgCl_2-treated$ MDCK cells. Conclusions: These results suggest that the activation of caspase-3 was involved in $HgCl_2-induced$ apoptosis. The release of cytochrome c from the mitochondria into the cytosol was also observed in the $HgCl_2-treated$ MDCK cells. These findings indicate that in MDCK cells, $HgCl_2$ is a potent inducer of apoptosis via cytochrome c release from the mitochondria.

• Nutrition Research and Practice
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• 제8권2호
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• pp.220-226
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• 2014

BACKGROUND/OBJECTIVES: Arsenic, which causes human carcinogenicity, is ubiquitous in the environment. This study was designed to evaluate modulation of arsenic induced cancer by resveratrol, a phytoalexin found in vegetal dietary sources that has antioxidant and chemopreventive properties, in arsenic trioxide ($As_2O_3$)-induced Male Wistar rats. MATERIALS/METHODS: Adult rats received 3 mg/kg $As_2O_3$ (intravenous injection, iv.) on alternate days for 4 days. Resveratrol (8 mg/kg) was administered (iv.) 1 h before $As_2O_3$ treatment. The plasma and homogenization enzymes associated with oxidative stress of rat kidneys were measured, the kidneys were examined histologically and trace element contents were assessed. RESULTS: Rats treated with $As_2O_3$ had significantly higher oxidative stress and kidney arsenic accumulation; however, pretreatment with resveratrol reversed these changes. In addition, prior to treatment with resveratrol resulted in lower blood urea nitrogen, creatinine and insignificant renal tubular epithelial cell necrosis. Furthermore, the presence of resveratrol preserved the selenium content ($0.805{\pm}0.059{\mu}g/g$) of kidneys in rats treated with $As_2O_3$. However, resveratrol had no effect on zinc level in the kidney relative to $As_2O_3$-treated groups. CONCLUSIONS: Our data show that supplementation with resveratrol alleviated nephrotoxicity by improving antioxidant capacity and arsenic efflux. These findings suggest that resveratrol has the potential to protect against kidney damage in populations exposed to arsenic.

• 대한약리학회지
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• 제32권2호
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• pp.259-267
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• 1996

In an attempt to dofine the early biochemical determinants that participate in the pathogenesis of glycerol-induced nephrotoxicity, especially focusing on oxygen free radicals and $N-acetyl-{\beta}-D-glucosaminidase$ (NAG) activity, we studied 24-hours urine outflow, 24-hours urinary protein excretion and urinary NAG activity after the injection of glycerol and also we studied malondialdehyde(MDA) level and superoxide dismutase(SOD) activity in the kidney of rats at 24hr after the injection of glycerol. Sprague-Dawley albino rats weighing 240 to 260 gm were injected intramuscularly with a 50% solution of glycerol(2ml/kg, 4ml/kg and 8ml/kg). The group treated with glycerol showed significantly lower urine outflow level and urinary protein excretion level and higher urinary NAG activity after the injection as compared to those of control group. Also the group treated with glycerol showed significantly higher MDA level and lower SOD activity at 24hr after the injection as compared to those of control group. These results suggest that the excessive oxygen free radicals resulting from the depression of SOD activity is an important determinant in the pathogenesis of glycerol-induced nephrotoxicity and higher urinary NAG activity is an index of renal tubular cell damage in the glycerol-induced nephrotoxicity.

• Journal of Nutrition and Health
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• 제53권1호
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• pp.1-12
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• 2020

본 연구에서는 고혈당으로 인해 유발되는 당뇨병성 신장병증의 대표적인 증상인 사구체 경화증을 완화시키는 nobiletin의 효능에 대해 알아보고자 하였다. 신장 세포인 HRMC를 이용하여 고혈당에서의 세포외 기질 축적 단백질의 발현과 경화에 관여하는 신호 전달 억제 효능을 확인한 결과 nobiletin은 고혈당의 자극에 의해 증가하는 섬유화 단백질인 collagen IV, fibronectin 그리고 CTGF의 발현을 억제하였으며, 여기에 관여하는 TGF-β1-Src-caveolin-1 신호 전달 경로를 통해 사구체 경화증을 억제하는 것을 확인하였다. 따라서 nobiletin은 고혈당으로 유도된 당뇨병성 신장병증에 있어 사구체 경화증을 예방하는 기능성 성분으로서의 활용 가능성을 확인하였다.

• Applied Microscopy
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• 제27권4호
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• pp.433-452
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• 1997

Mongolian gerbil (Meriones unguiculatus) has been as an animal model for studing the neurological diseases such as stroke and epilepsy because of the congenital incompleteries in Willis circle, as well as the investigation of water metabolism because of the long time-survival in the condition of water-deprived desert condition, compared with other species animals. In order to accomplish the this research, first of all another divided the laboratory animals 5 groups of which each group include the 5 animals. In this study were investigated the histological structure in the kidney, measured the plasma osmolalities at the time of sacrifice of indivisual animals, and the body weights every day during water-deprived. The results obtained in this study were summarized as followings: 1. The body weights and decreasing rates of the body weight in water-deprived mongolian gerbil groups were continuosly decreased. 2. The plasma osmolalities were increased from the 5th water-deprived day, after then the gradually increasing reached nearly its equilibrium state at the 10th water-deprived day. 3. The urine volumes were abruptly decreased from the 2th water-deprived day, after then the gradually decreasing patterns were reached nearly its equilibrium state at the 10th day, and stopped the 11th day. 4. In the light microscopical observation of the kidney, glomerular capillary loop thickening, mesangial matrix increasing, sclerosis, glomerular cystic atrophy, interstitial fibrosis, tubular dilatation, mononuclear interstitial inflammation, interstitial mineralization, and hyperplasia of the collecting duct epithelium in the cortex area, were observed from the 10th water deprived day, and the lesions were gradually severe changed as the time lapse. 5. In the electron microscopical findings of the kidney, the degenerative changes of endothelial cell, podocyte and mesangial cell in glomeruli were initially observed on the 10th water-deprived day as well as the degeneration of microvilli and intracellular organelle in the renal tubules.

• 대한한방내과학회지
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• 제26권1호
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• pp.12-47
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• 2005

First, mice were dosed with 50mg/kg of streptozotocin(STZ) twice every 24 hours to cause high blood-sugar. Then, after three days, mice were injected with 100mg/kg of STZ again. Two different dosages of Saengjihwangeumja-gami were given to the experiment groups: SA group, 15mg/kg/day, and SB group, 90mg/kg/day, in order to determine the effects of Saengjihwangeumja-gami, which has been known to be good for DM(Diabetes Mellitus). By observing weight and blood-sugar level changes, blood tolerance, the numerical value of BUN(Blood Urea Nitrogen) and creatinine in blood, and through light-electronicmicroscopic and immunohistologic investigations of pancreas and kidneys, the following results were obtained: 1. The experiment groups showed a high suppressive effect of weight-loss. 2. The experiment groups' blood-sugar and blood tolerance showed an effective lowering of blood-sugar levels. 3. The experiment groups did not show any noticeable change in the numerical value of BUN and creatinine in blood compared with that of the control groups. 4. The experiment groups showed a higher Insulin positive reaction of pancreatic islets ${/beta}-cell$ than the control groups. 5. The experiment groups showed a higher immuno-reaction against IGF- II than the control groups. 6. Observation of apoptosis of the pancreatic islets showed that the cells of experiment groups were less injured compared with those of the control groups, and fewer apoptag-positive reaction cells were seen in experiment groups than in the control groups. 7. Uunder electron-microscopy, the insulin-containing granules in pancreatic islets ${/beta}-cells$ had increased more in the experiment groups than in the control groups. 8. Under light microscopy, the injury on the inner & outer membrane of the glomerulus and epithelial cells of capillaries and cells among vessels were fewer in the experiment groups than in the control groups. 9. More apoptag-positive reaction cells in the kidney were seen in the control groups than in the experiment groups. 10. PAS-positive reaction substances had increased more in the substrate among the vessels of a glomerulus belonging to the control group than those of the experiment group. 11. Uunder electron-microscopy, the nucleonic membrane, nucleoplasm and mitochondria of proximal and distal renal tubular were more injured in the control groups than in the experiment groups. In conclusion, strong evidence for the efficacy of Saengjihwangeumja-gami in lowering blood-sugar, and in recovery and generation of pancreatic tissues injured by DM was observed. Results suggest Saengjihwangeumja-gami is an effective treatment for DM. Further study of the principles of blood-sugar dropping effects of Saengjihwangeumja-gami are needed, as well as further study of recovery and regeneration of pancreatic tissues injured by DM.

• 한국식품과학회지
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• 제29권6호
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• pp.1264-1268
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• 1997

알루미늄 화합물 종류에 따라 흰쥐의 신장에 축적된 알루미늄 함량과 그로 인한 신장조직의 변화를 조사하기 위하여 S-D계 수컷 75마리를 5개 그룹 즉 대조군, 250 ppm $AlCl_3$ 500 ppm $AlCl_3$ 250 ppm $Al_2(SO_4)_3$ 500 ppm $Al_2(SO_4)_3$로 나누어 2주 동안 투여한 후 그 결과를 조사하였다 신장의 알루미늄량은 $AlCl_3$ 투여군은 $64.12{\sim}91.98\;ppm$ 이었고, $Al_2(SO_4)_3$ 투여군은 $113.58{\sim}135.49\;ppm$으로 $AlCl_3$보다 $Al_2(SO_4)_3$ 투여군에서 더 많이 축적되었다. 신장조직에서 $AlCl_3$, 투여군은 세뇨관 부위의 갑상선화와 간질세포내의 염증세포의 침윤, 수질의 세뇨관 파괴부위에 알루미늄이 침착되었고, $Al_2(SO_4)_3$ 투여군에는 피질에 심한 출혈, 사구체의 파괴 및 염증부위에서 알루미늄 침착이 관찰되었다.

• 한국식품영양과학회지
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• 제43권1호
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• pp.47-54
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• 2014

본 연구는 녹차폴리페놀이 시스플라틴의 항암작용과 신장 독성에 미치는 영향을 유방암 세포(EMT6)와 암세포 이식마우스를 이용하여 in vitro와 in vivo 실험으로 관찰하였다. 배양한 EMT6 세포에서 녹차폴리페놀은 시스플라틴에 의한 세포 독성을 증가시켰다. 마우스에 EMT6 세포를 주사하여 유발된 종양의 크기가 시스플라틴군(CP)보다 시스플라틴+녹차폴리페놀군(CP+GTP)에서 유의하게 작았고, 종양조직 p53와 caspase-3 활성화가 시스플라틴군(CP)보다 시스플라틴+녹차폴리페놀군(CP+GTP)에서 유의하게 높았으며, 신장 GGT와 AP 활성은 시스플라틴군(CP)보다 시스플라틴+녹차폴리페놀군(CP+GTP)에서 유의하게 높았고, 신장 조직학적 소견에서 신세뇨관 확장과 괴사가 시스플라틴군(CP)보다 시스플라틴+녹차폴리페놀군(CP+GTP)에서 유의하게 낮았다. 이상의 결과 녹차폴리페놀은 EMT6 유방암 세포를 이용한 in vitro 및 in vivo 실험에서 시스플라틴의 항암작용을 증강시키면서 신장에 대한 독성 부작용은 감소시키는 효과가 있는 것으로 추측된다. 녹차폴리페놀의 시스플라틴 항암작용 증강과 신장 독성 억제 및 감소 효과는 시스플라틴에 의한 암 치료 시 화학요법제의 보조제로서 이용가치가 있는 것으로 생각되며, 항암화학요법제에 대한 보조제로의 개발을 위해서는 대규모 동물실험을 통한 효과 입증 및 부작용에 대한 실험과 임상연구가 뒷받침되어야 할 것으로 사료된다.