• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.284-291
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• 1997

The pharmacokinetics and tissue distribution of DWP20367 (1-cyclopropyl-6-fluoro-8-chloro-7-(2, 7-diazabicyclo[3,3,0]tract-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone, were examined in rats and beagle dogs after a single intravenous and oral administration. Analysis of DWP20367 in plasma, tissue, and urine was determined by both HPLC and microbiological assay (bioassay). The plasma concentration-time curves of the drug in rats and beagle dogs were biexponentially declined. The terminal half-life (t$_{1}$2$\beta$/) of the drug in rats was about 60.1 $\pm$7.3 min (i.v.) and 61.3 $\pm$ 12.4 min (p.o.) in bioassay, and 86.3 $\pm$19.8 min (i.v.) and 50.9$\pm$ 14.9 min (p.o.) in HPLC. In beagle dogs, half-life of the drug determined by bioassay was about 121.8$\pm$6.2 min (i.v.) and 111.0$\pm$7.6 min (p.o.). The volume of distribution at steady-state (Vd$_{ss}$ ) was 243.8$\pm$74.1 ml/kg (bioassay) and 339.2$\pm$84.3 ml/kg (HPLC) in rats, and 1587.5 $\pm$536.9 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl$_{t}$) of DWP20367 was 3.4 $\pm$ 0.4 ml/min/kg (bioassay) and 2.4$\pm$0.4 ml/min/kg (HPLC) in rats, and 12.3$\pm$ 1.0 ml/min/kg (bioassay) in beagle dogs, respectively. The extent of bioavailability after oral administration was 89.1%(bioassay) and 79.9% (HPLC) in rats, and 78.7% (bioassay) in beagle dogs. Urinary recovery (24-h) assayed by bioassay was 0.7% (p.o.) and 1.2% (i.v.) in rats, and 0.8% (p.o.) and 1.0% (i.v.) in beagle dogs. In rats, 24-h fecal recovery determined by bioassay was 11.2% (p.o.) and 0.1% (i.v.). Rat and human serum protein binding ratios at 2$\mu$g/ml were about 90~91%. This drug determined by bioassay was also distributed by the order of liver, kidney, lung, heart, spleen and muscle 30 min after oral administration.on.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.7
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• pp.1126-1132
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• 2004

The present study was undertaken to evaluate the effect of functional food, which was processed with fermented soybean as main ingredient (FS), on the body weight, organ weight, plasma glucose, and plasma lipid in diabetic rats caused by streptozotocin (STZ). The body weight was decreased more slowly in the FS group than in the diabetic, and the food intake increased significantly in all diabetic groups. The food efficiency was very low in all diabetic groups, but increased significantly in the FS groups than diabetic control (p＜0.05). In comparing the weight of organ, the weight of liver and kidney were increased in all diabetic groups than in the control, and decreased slightly in FS groups. The weight of heart and spleen were not different among all test groups. In the oral glucose tolerance test, the blood glucose in the diabetic group was the highest in 60 minutes. And the blood glucose in the FS group was the highest in 30 minutes, and decreased significantly after 120 minutes to the level of fasting glucose. The glucose in serum was decreased significantly in the FS groups fed the functional food for 4 weeks, compared to the diabetic control (p＜0.05). Total cholesterol, triglyceride and atherogenic index (AI) in serum were significantly higher in diabetic control, compared to the normal (p＜0.05), and decreased by 16.4％, 15.4％ and 48.3％, respectively, in the FS fed 400 mg/kg of functional food. HDL-cholesterol was increased significantly in the FS-400, compared to the diabetic control. These results support that functional food using fermented soybean improve glucose and lipid metabolism in diabetic rats.

• Toxicological Research
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• v.25 no.3
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• pp.140-146
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• 2009

This study was performed to evaluate the toxicity of cadmium selenide for a period of 28 days in Sprague-Dawley rats. Each of 10 healthy male and females rats per group received daily oral administration for 28-day period at dosage levels 30, 300 and 1,000 mg/kg of body weight. Mortality and clinical signs were checked, and body weight, water intake and food consumption were also recorded weekly. There were no dose-related changes in food consumption or urine volume. All animals survived to the end of study with no clinical signs or differences in body weight gain observed when compared with the control group. At the end of study, all animals including control group, were subjected to necropsy. Blood samples were collected for hematology tests including coagulation time and biochemistry analysis. Blood coagulation time and relative organ weight were unaffected by all received doses. White Blood Cell (WBC) counts significantly increased in the 300 mg/kg administered male animal group when compared to the control. Monocyte (MO) value were also increased significantly in both 300 and 1,000 mg/kg male animal group. However, Mean Corpuscular Volume (MCV) were significantly decreased compared with the control in the 1,000 mg/kg dose groups for male and female animals. Mean Corpuscular Hemoglobin (MCH) decreased significantly for female in the 300 and 1,000 mg/kg group compared to the control. Blood biochemical values of Inorganic phosphorus (IP) were significantly increased in both the 300 and 1,000 mg/kg dose groups in male animals when compared to the control. Creatinine (CRE) levels indicated significant increase in kidney function for the female, 30 mg/kg dose group when compared with control. There was a significant decrease in thymus absolute organ weight in the female, 1,000 mg/kg dose group when compared with control. Histopathological findings revealed no evidence of injury related to cadmium selenide except for one case of focal hepatic inflammation in the high dose (1,000 mg/kg) group. One case of lung inflammation was also seen in the control group. Basis on these result, the No Observable Adverse Effect Level (NOAEL) of cadmium selenide was determined to be more than 1,000 mg/kg/day for male and female rats under conditions in this study.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.119-127
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• 2005

Purpose : Podocytes are critical in maintaining the filtration barrier of the glomerulus and are dependent on the integrity of slit diaphragm(SD) proteins including nephrin, p-cadherin, and others. Diabetic proteinuric condition demonstrates defects in SD molecules as well as ultrastructural changes in podocytes. We examined the molecular basis for this alteration of SD molecules especially on P-cadherin as a candidate regulating the modulation of pathogenic changes in the barrier to protein filtration. Methods : To investigate whether high glucose and AGE induce changes in SD, we cultured rat GEpC under normal(5 mM) or high glucose(30 mM) and AGE- or BSA-added conditions and measured the change of P-cadherin expression by Western blotting and RT-PCR. Results : We found that administration of high glucose decreased the P-cadherin production significantly in the presence or absence of AGE by Western blotting. In RT-PCR high glucose with or without AGE also significantly decreased the expression of P-cadherin mRNA compared to those of controls. Such changes were not seen in the osmotic control. Conclusion : We suggest that high glucose with or without AGE suppresses the Production of P-cadherin at the transcriptional level and that these changes nay explain the functional changes of SD in diabetic conditions. (J Korean Soc Pediatr Nephrol 2005;9:119-127)

• Childhood Kidney Diseases
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• v.6 no.1
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• pp.85-91
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• 2002

Purpose: Phosphodiesterase (PDE) inhibitor increases the cellular content of cAMP, and cAMP suppresses connective tissue growth factor (CTGF) expression induced by TGF-${\beta}1$. Therefore, we investigated whether PDE inhibitor suppresses renal fibrosis without suppression of TGF-${\beta}1$. Materials and Methods : Renal interstitial fibrosis was produced by ligation of left ureter in Sprague-Dawley rats. Cilostazol, a selective PDE3 inhibitor, and dipyridamole, a hybrid PDE5, PDE6, and PDE8 inhibitor, were provided in drinking water for 7 days. In addition to the Masson-trichrome score of renal tissue, the concentration of fibronectin and TGF-${\beta}1$ in renal tissue- conditioned media was measured by ELISA. Results : Masson- trichrome score and fibronectin concentration were significantly lower in cilostazol-treated group compared to the control group (P<0.05). Though dipyridamole treatment seemed to suppress the Masson- trichrome score and fibronectin concentration too, the decrements were not statistically significant. There was no difference in TGF-${\beta}1$ concentration among the groups. Conclusion: A selective PDE3 inhibitor cilostazol suppresses renal fibrosis without alteration of TGF-${\beta}1$ expression. (J Korean Soc Pediatr Nephrol 2002 ;6 : 85-91)

• Journal of Society of Preventive Korean Medicine
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• v.3 no.2
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• pp.151-170
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• 1999

This study was to investigate the metal accumulation from SipJeonDaeBo-Decoction to rat blood of Sprague Dawley. 1. There were no significance in body weight, water dose feed ingestion quantity, liver, kidney, brain, bone weights between the control and the experimental groups. Under the experiment with drinking waters was no metal ${\sim}\;0.65mg/L$ detected. Metal level within feed found 0.0001-376.983mg/kg. 2. In the pack of SipJeonDaeBo-decoction, there detected no metal ${\sim}2.086mg/L$ 3. After P.O(per os) SipJeonDaeBo-decoction, As is detected $2.390{\pm}0.812mg/kg$ in blood; Cd $0.001{\pm}0.001mg/kg$, Co $0.003{\pm}0.001mg/kg$, Cr $0.432{\pm}0.234mg/kg$, Cu $1.013{\pm}0.373mg/kg$, Fe $426.293{\pm}114.842mg/kg$, no Hg, Mn $0.109{\pm}0.082mg/kg$, Ni $0.122{\pm}0.068mg/kg$, Zn $3.584{\pm}1.270mg/kg$. 4. The concentration of Hazardous heavy metal (As, Cd, Co, Cr, Hg, Ni, Pb) within blood control group is searched $0.488{\pm}0.138\;mg/l$; experiment I group $0.432{\pm}0.080mg/l$, experiment II group $0.588{\pm}0.213mg/l$. In the concentration of non hazardous heavy metal(Cu, Fe, Mn, Zn) control group $101.409{\pm}6.832mg/l$; experiment I group $96.062{\pm}5.732\;mg/l$, experiment II group $125.139{\pm}044.820mg/l$. 5. Correlation among every metal in blood Zn and Cr was 0.87956 ; Cd and As -0.02316, Pb and As -0.08738, Ni and As 0.07824, Mn and As 0.07824, Mn and Cd 0.04999. Briefly under the injection of SipJeonDaeBo-decoction, this study was defined within safety in blood level by P.O. during 10 days.

• Journal of Nutrition and Health
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• v.35 no.1
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• pp.5-14
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• 2002

Alteration in the syntesis or enhanced inactivation of nitric oxide(NO) can induce impairment of endothelial cell function. Insulin dependent diabetes mellitus(IDDM) is characterized by impaired endothelial function and vascular disease. NO is produced through L-arginine pathway To elucidate the hypothesis that the decreased production on NO in IDDM reflects vascular damage and the NO production can be manipulated by either dietary fat(7% of kg diet) or the oral supplementation with L-arginine(2g/kg bw), plasma markers for vascular endothelial damage and plasma lipid profiles were measured in streptozotocin(STZ)-induced diabetic rats. Diabetic or normal Sprague-Dawley rats were fed 6 different experimental diets for 4 weeks(SO : soybean oil, SOA: soybean oil + L-arginine supplementation, BT : beef tallow, BTA_ beef tallow + L-arginine supplementation, OV olive oil, OVA : olive oil + L-arginine supplementation). Plasma glucose, total cholesterel, HDL-cholesterol, LDL-cholesterol and triglyceride were measured. Endothelial markers, plasma von Willebrand factor(vWf), thromboxane B$_2$, and 6-keto PGF1$\alpha$ of aorta were measured by ELISA. Plasma NO production was evaluated through the measurement of nitrite by EIA. Feeding saturated fatty acid(SFA, BT) increased relative liver size(RLS) in diabetic rats compared to either polyunsatunted fatty acid(PUFA, SO) or monounsaturated fatty acid(MUFA, OV) The supplementation of L-arginine inhibited the liver and kidney enlargement in olive oil find diabetic rats. Plasma glucose was lower in diabetic animal find the olive oil compared to fed beef tallow and the supplementation L-arginine decreased it in diabetic rats find beef tallow significantly(p < 0.05). Plasma TXB$_2$ levels were increased due to diabetes and the value of beef tallow group showed highest value. Plasma vWf concentration of beef tallow group was higher value in normal rats and was elevated more in diabetes. In diabetic groups, the vWf concentration of olive oil group was lower than beef tallow or soybean oil group. The supplementation of L-arginine in diabetic rats decreased plasma TXB$_2$ and vWf levels significantly(p < 0.05). NO production was higher in normal olive oil fed rats and was tend to be decreased in diabetic rats and the supplementation of L-arginine recovered to normal value(p < 0.05), Olive oil supplemented with L-arginine tended to lower plasma total cholesterol and LDL-cholesterol after 4 week treatment. These results suggest that generalized vascular endothelial changes based on plasma TXB$_2$and vWf occurs in diabetic rats. and olive oil with L-arginine supplementation contributes to a better control of the hyperglycemia, endothelial changes and hypercholesterolemia accompanying diabetes as compared with beef tallow or soy bean oil in this rat model.

• Journal of Pharmacopuncture
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• v.18 no.4
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• pp.45-50
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• 2015

Objectives: In this study, we investigated the 4-week repeated-dose oral toxicity of gami-jakyak gamcho buja decoction (Mecasin) to develop safe treatments. Methods: In order to investigate the 4-week oral toxicity of Mecasin, we administered Mecasin orally to rats. Sprague-Dawley (SD) rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of Mecasin of 500, 1,000, and 2,000 mg/kg of body weight were administered to the experimental groups, and a dose of normal saline solution of 10 mL/kg was administered to the control group. We examined the survival rate, weight, clinical signs, and gross findings for four weeks. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths occurred in any of the four groups. No significant changes in weights or food consumption between the control group and the experimental groups were observed. Serum biochemistry revealed that some groups showed significant decrease in inorganic phosphorus (IP) (P < 0.05). During necropsy on the rats, one abnormal macroscopic feature, a slight loss of fur, was observed in the mid dosage (1,000 mg/kg) male group. No abnormalities were observed in any other rats. In histopathological findings, the tubular basophilia and cast of the kidney and extramedullary hematopoiesis of the spleen were found. However, those changes were minimal and had occurred naturally or sporadically. No other organ abnormalities were observed. Conclusion: During this 4-week, repeated, oral toxicity test of Mecasin in SD rats, no toxicity changes due to Mecasin were observed in any of the male or the female rats in the high dosage group. Thus, we suggest that the doses in a 13-week, repeated test should be 0, 500, 1,000, and 2,000 mg/kg respectively.

• The Korean Journal of Physiology
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• v.23 no.1
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• pp.23-34
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• 1989

Gentamicin (GM) is a polybasic, aminoglycoside antibiotic used frequently for the treatment of serious gram-negative infections. The major limiting factors in the clinical use of GM as well as other aminoglycoside antibiotics are their nephrotoxicity and ototoxicity. The primary mechanism of cell injury in aminoglycoside toxicity appears to be the disruption of normal membrane function and the inhibition of $Na^{+}-K^{+}$ ATPase activity. There are both indirect and direct evidences which suggests that the effect of aminoglycoside antibiotics on $Na^{+}-K^{+}$ ATPase may explain, or contribute to, their toxicity. It has been shown that aminoglycoside reduce total ATPase activity (Kaku et al., 1973) and $Na^{+}-K^{+}$ ATPase activity (linuma et al., 1967) in the stria vascularis and spiral ligament of the guinea-pig cochlea. Lipsky and Lietman (1980) reported that aminoglycoside antibitoics inhibited the activity of $Na^{+}-K^{+}$ ATPase in microsomal fractions of the cortex and medulla of the guinea-pig kidney, isolated rat renal tubule and human erythrocyte ghosts. The present invstigation was undertaken to elucidate the mechanism of GM on human erythrocytes by examining its effect on $Na^{+}-K^{+}$ ATPase activity, actives sodium and potassium transport across red blood cell and $^{3}H-ouabain$ binding to red blood cell membranes. The results obtained are summarized as follows: 1) CM inhibited significantly both the activity of total ATPase and $Na^{+}-K^{+}$ ATPase at all concentrations tested. 2) GM inhibited active $^{22}Na$ efflux across red blood cell. When ouabain is present, the rate of $^{22}Na$ efflux was completely inhibited. When both GM and ouabain were added, the inhibitory effect of active $^{22}Na$ efflux was more pronounced. 3) Active $^{86}Rb$ influx was inhibited significantly by GM. In the presence of ouabain, the rate of $^{86}Rb$ influx is markedly inhibited. But $^{86}Rb$ influx is not appreciably altered by the presence of both GM and ouabain. 4) In the presence of GM, $^{3}H-ouabain$ binding to red blood cell membrane increased. From the above results, it may be concluded that the inhibition of active sodium and potassium transport across red blood cell by gentamicin appears to be due to the inhibition of $Na^{+}-K^{+}$ ATPase activity and an increase in ouabain binding to red blood cell membranes.

• Journal of Life Science
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• v.19 no.3
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• pp.322-326
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• 2009

Glutathione is a well-known chemotherapeutic agent and a popular nutritional supplement for liver disease and oxidative stress. Our previous studies reported the suppressive effects of the glutathione-enriched Saccharomyces cerevisiae FF-8 (FF-8) strain on carbon tetrachloride- and alcohol-induced oxidative stress in rats. The purpose of the current study was to investigate the effect of the FF-8 strain on lipid peroxidation in tissues of rats with orotic acid (OA)-induced fatty liver. OA treatment showed a significant decrease in body weight gain compared to the normal diet, and simultaneous addition of FF-8 and OA had the same effect. OA treatment produced an increase in liver weight, however, this also increased with simultaneous addition of FF-8 and OA. Liver lipid peroxidation was significantly increased by OA, but was significantly decreased by FF-8 strain treatment. This same tendency was found in the kidney and heart. Concentration levels of hepatic glutathione and zinc are known to be closely associated with the antioxidant system, and OA treatment led to reductions in liver glutathione and zinc concentrations, whereas these were significantly increased by FF-8 strain treatment in OA feeding rats. These results suggest that the glutathione-enriched S. cerevisiae FF-8 strain may positively mediate orotic acid-induced oxidative stress by enhancing glutathione and zinc levels in rat livers.