• Toxicological Research
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• v.20 no.4
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• pp.349-357
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• 2004

This study was performed to evaluate repeated-dose toxicities of CONP01 in Sprague-Dawley rats. CONP01, a new antiarthritic agent was administered orally to rats at dose levels of 0, 125, 500 and 2,000 mg/kg/day for 4 weeks. In present study, there were no dose response changes in mortality, clinical signs, body weight changes, food and water consumption, ophthalmoscopy, organ weights, urine analysis, hematological findings, and biochemical examination of all animals treated with CONP01. Gross and histopathological findings revealed no evidence of specific toxicity related to CONP01. These result suggest that no observed adverse effect level (NOAEL) of CONP01 may be over 2,000 mg/kg in rats.

• Archives of Pharmacal Research
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• v.17 no.6
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• pp.428-433
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• 1994

The methabolism and phamacokinetics of a mixed disulfide S-(N, N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine (AC-DDTC) were studied in rats. Two metabolites of AC-DDTC following iv and po administration were indentified in plasma and liver by HPLC and GC, namely N, N-diethyldithiocarbamate (DDTC) and the methyl ester of DDTC (Me-DDTC). AC-DDTC was very unstable in vivo and could not be detected neither in plasma nor in urine. Pharmacokinetic parameters of DDTC following intravenous administration of AC-DDTC (20 mg/kg) were calculated. DDTC has a low affinity to rat tissue and the body clearance was $9.0{\pm}3.4mkl/mim/kg$. The mean residence time (MRT) was $11.5{\pm}16.3 min$. After oral administration of 20 mg/kg AC-DDTC, maximal plasma concenttion ($C_{max}$) was $3.8{\pm}0.2 nmol/ml$ and the bioavailability was 7.04%. $C_{max}$ for DDTC at a dose of 120 mg/kg. AC-DDTC was $40.1{\pm}2.2 nmol/ml$. ART was $47.1{\pm}2.8min$.at a dose of 20 mg/kg and $110.5{\pm}6.0 min$ at 120 mg/kg.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.374-380
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• 2000

Propentofylline (PPF, 3-methyl-1-(5-oxohexyl)-7-propylxanthine) has been reported to be a compound for treatment of both vascular dementia and dementia of the Alzheimer type. The short half-life (about 15 min) of PPF at the terminal elimination phase and poor bioavailability after oral administration of PPF to rabbits (Kim et al., 1992) suggest in part that this drug takes the extensive first-pass metabolism in the liver. In addition, the metabolic pathway for PPF remains unclear. The objective of this experiment is to identify urinary metabolites of PPF in rats. For the identification of the metabolites, rat urine was collected after oral administration of 100${m}g/kg$ PPF. PPF metabolite, 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine, was synthesized and confirmed by gas chromatography/mass spectroscopy (GC/MS) and $^1H$ nuclear magnetic resonance spectroscopy. The urinary metabolites of PPF were extracted with diethyl ether and identified by electron impact and chemical ionization GC/MS. One urinary metabolite was confirmed to be 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine by synthesized authentic compound. Several metabolites of monohydroxy- and dihydroxy-PPF were identified based on mass fragmentation of both intact and trimethylsilylated derivatives of PPF metabolites and the novel structure of these metabolites is suggested based on mass spectra.

• Journal of Pharmacopuncture
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• v.3 no.2
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• pp.41-54
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• 2000

This study was undertaken to determine if Plantaginis Semen Herbal Acupuncture(PSA) has a protective effect against glycerol-induced acute renal failure in rats. Rats were dehydrated for 24hr and then injected with 8 ml/kg of $50\%$ glycerol, one-half of dose in each hindlimb muscle. In experiments for PSA effect, rats received 0.1 ml of PSA extraction in both sides of corresponding Shenso($BL_{23}$) of human body for 3 days after injection of glycerol. The experimental group were di vided into the Normal group, the Control group, the PSA group. Glycerol injection decreased glomerular filtration rate and increased urine volume, serum creatinine, BUN level and fractional excretion of glucose, $Na^+$, $K^+$ and $CI^-$. These result show that glycerol injection result in acute renal failure. PSA significantly increased glomerular filtration rate and significantly decreased serum creatinine, BUN level and fractional excretion of glucose, $Na^+$ and $CI^-$ as compared Control group. This suggests that PSA could be used in prevention and treatment of acute renalfailure. However, the precise mechanisms of PSA protection remain to be determined.

• Biomolecules & Therapeutics
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• v.14 no.4
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• pp.194-201
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• 2006

The general pharmacological properties of GCSB-5, a herbal formulation consisting of 6 Oriental herbs(Ledebouriellae Radix, Achyranthis Radix, Acanthopanacis Cortex, Cibotii Rhizoma, Glycine Semen and Eucommiae Cortex), were investigated in mice, rats, guinea pigs and rabbits. The administration of GCSB-5 had no effect on general behavior, and did not influence the central nervous system. Mean blood pressure, heat1 and respiratory rate and contractile response of the isolated guinea pig atrium were unaffected by the treatment of GCSB-5. Addition of GCSB-5 did not cause spontaneous relaxation and contraction of the isolated guinea pig ileum and rat uterus. And also, GCSB-5 had no effect on the gastrointestinal system and the blood system of the animals examined in this study. GCSB-5, at higher doses(1,000 and 3,000 mg/kg), increased the urinary excretion of electrolytes, however, the urine volume and pH in rats were unaffected. Taken together, these results indicate that GCSB-5 does not induce any adverse effects in experimental animals and is expected to have no significant general pharmacological activities.

• Journal of Microbiology and Biotechnology
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• v.31 no.9
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• pp.1281-1287
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• 2021

Clinical and preclinical studies have reported that Lactobacillus gasseri BNR17, a probiotic bacterial strain isolated from human breast milk, reduces body weight and white adipose tissue volume. In order to further explore the actions of L. gasseri BNR17, we investigated the anti-menopausal effects of L. gasseri BNR17 in an ovariectomized (OVX) rat model. The serum alanine aminotransferase levels of the rats in the OVX-BNR17 group were lower than those of the rats in the OVX-vehicle only (OVX-Veh) group. Upon administration of L. gasseri BNR17 after ovariectomy, calcitonin and Serotonin 2A levels increased significantly, whereas serum osteocalcin levels showed a decreasing tendency. Compared to the rats in the OVX-Veh group, those in the OVX-BNR17 group showed lower urine deoxypyridinoline levels, lower pain sensitivity, and improved vaginal cornification. Furthermore, L. gasseri BNR17 administration increased bone mineral density in the rats with OVX-induced femoral bone loss. These results suggest that L. gasseri BNR17 administration could alleviate menopausal symptoms, indicating that this bacterium could be a good functional probiotic for managing the health of older women.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.2
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• pp.176-180
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• 2005

This study was conducted to examine effect dietary protein and calcium levels on calcium metabolism of the rat. Weaned 6-week old male rats were divided into 4 groups and were fed experimental diets for six weeks. Experimental groups were HPNC group-high protein normal calcium (protein: 400 g/kg diet, calcium: 0.5%), HPLC group-high protein low calcium (protein: 400 g/kg diet, calcium: 0.1%), NPNC group-normal protein normal calcium (protein: 200 g/diet, calcium: 0.5%), NPLC group-normal protein low calcium (protein: 200 g/diet, calcium: 0.1%). The calcium excretion in urine was higher in high protein group than in normal protein group, and it was highest in HPLC group. The activation of alkaline phophatase had a tendency to low in normal calcium group, and the concentration of parathyroid hormone (PTH) was the lowest in HPLC group. The deoxypyridinoline (DPD) concentration of urine was investigated as the highest in HPLC group and it was significantly lower in HPNC group that consumed normal calcium. The bone density of the femur was the highest in NPNC group and the lowest in NPLC group. As the results of this study, calcium excretion in urine and DPD density were the highest and the bone density was the lowest in HPLC group. It may suggest that the deficiency of calcium causes adversely effect in calcium metabolism upon consuming high protein diet. Therefore, it should be emphasized to consume enough calcium to prevent the hindrance of skeletal metabolism caused by deficiency of calcium upon consuming high protein diet.

• YAKHAK HOEJI
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• v.41 no.3
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• pp.335-344
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• 1997

The absorption, distribution and excretion of $^{14}C$ labeled YH1885 {5,6-Dimethyl-2(4-fluorophenylamino)-4-(1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine hydroc hloride), a new proton pumpinhibitor, were investigated in rats after a single administration of $^{14}C$-YH1885. 1. After intravenous administration of 5mg/kg, the blood level of radioactivity declined in a biphasic fashion with the mean terminal elimination half-life of 12.4hr. 2. After oral administration of 20mg/kg, the maximum blood level of radioactirity was reached at 4.0hr in female rats. The blood level of radioactivity-time profiles in male and female rats were similar, and the absorptionof $^{14}C$-YH1885 was not affected by food. 3. Appproximately 89% and 1% of radioactivity of the total dose were excreted in feces and urine, respectively. 4. Biliary excretion of radioactivity was 47.9% of the dose. Enterohepatic circulation of radioactivity was 49.6%. 5. Radioactivity was excreted maily into feces via bile. 6. The concentration of radioactivity in most tissues reached the peak level at 4.0hr after dosing, and then declined. Autoradiograms of male rats showed that the radioactivity levlels in the fat, harder's gland, liver and G-Itract were higher than those in the other tissues and the elimination of radioactivity from fat and liver was slow. 7. Autoradiograms of a pregnant rat showed that radioactivity was transferred to mammary gland, placenta and fetus. The radioactivity level in the mammary gland was higher than that in the blood.

• The Korean Journal of Physiology
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• v.15 no.2
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• pp.103-109
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• 1981

In order to determine the dose-response relationship of ethanol on blood pressure and renal function, 2 doses of ethanol were intubated into albino rats. For a direct measurement of arterial blood pressure, a polyethylene catheter(PE 10) was implanted in the abdominal aorta, and the other end of the catheter was pulled out of the back of the neck. The experiment was conducted after the rats recovered from the surgery. After emptying their bladders, the rats were placed in a metabolism cage. Mean arterial pressure (MAP) was measured and arterial blood samples were collected through the catheter. Following the collection of the control urine sample, 1 ml of 10 g% (low dose), or 30 g% (high dose) of ethanol/100 g BW was intubated. 1 ml of water/100 g BW was intubated into the control group. MAP and blood samples were taken every hour, and urine samples were collected every 90 min for 3 hours. Blood alcohol concentrations reached a peak at 1 hour (low dose: $105.0{\pm}7.5$, high dose: $214.7{\pm}20.2\;mg%$) and decreased linearly thereafter. Following alcohol ingestion, MAP began to decrease at 15 min and remained at a significantly low level thoughout the 3 hours experimental period(low dose: $112{\pm}2{\rightarrow}102{\pm}4$, high dose: $117{\pm}2{\rightarrow}100{\pm}8\;mmHg$). Urine Flow increased markedly during the first 90 min of ethanol ingestion (low dose: $0.88{\pm}0.20{\rightarrow}1.04{\pm}0.22$, high dose: $0.56{\pm}0.11{\rightarrow}1.35{\pm}0.18\;ml/1.5\;hr$) and decreased during the second 90 min period(low dose: $0.25{\pm}0.06$, high dose: $0.22{\pm}0.06\;ml/1.5\;hr$). Urine flow of the control group decreased gradually during the experiment $(0.88{\pm}0.10{\longrightarrow}0.59{\pm}0.09{\rightarrow}0.45{\pm}0.09\;ml/1.5\;hr)$. These results indicate that the blood-pressure-lowering and diuretic effects of ethanol are dose-related: higher doses of ethanol produce a greater decrease in blood pressure and greater diuresis.

• Herbal Formula Science
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• v.16 no.1
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• pp.147-168
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• 2008

HYTE (Hyeonggaeyeongyotang Extract), a polyherbal formula has been used as folk medicine, 28days repeat oral dose toxicity was tested in SD rats according to KFDA Guideline[2005-60]. Methods : In this study, mortality, clinical signs, body weight and gains, food and water consumption, ophthalmologic observation, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathological observations were conducted during 28days of dosing periods. Results: 1. No HYTE treatment-related mortalities and clinical signs were detected in all dosing levels tested in male and female rats during the whole experimental periods. 2. No HYTE treatment-related changes on body weight, gains and food consumption were detected in all dosing levels tested in male and female rats during the whole experimental periods except for 2000mg/kg-dosing female groups in which significantly increase of body weight, gains, food and water consumption were detected compared to that of vehicle control in some points. 3. No HYTE treatment-related changes on ophthalmologic examination were detected in all dosing levels tested in male and female rats. 4. No HYTE treatment-related changes on urinalysis were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing female groups in which, significantly increase of urine volume and related decrease on the urine specific gravity were detected as secondary effects of increase on the water consumptions not HYTE treatment-related toxicological signs. 5. No HYTE treatment-related changes on hematology were detected in all dosing levels tested in male and female rats except for increases in the total WBC count and lymphocytes of 2000mg/kg-dosing male and female groups with decrease of large unstained cells as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. 6. No HYTE treatment-related changes on serum biochemistry were detected in all dosing levels tested in male and female rats. 7. No HYTE treatment-related changes on gross findings, organ weight and histopathology were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing male and female groups in which, spleen and thymus organ weights, hypertrophy at gross observation and hyperpalsia of lymphoid cells and follicles at histopathological observation in spleen and thymus were detected as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. Conclusions : Based on these results, the NOAEL and MTD of HYTE in SD rats were considered as over 2000mg/kg, respectively at 28days repeat oral dose toxicity test because most of these findings were considered as results of pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs or secondary effects.