• Toxicological Research
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• 제20권4호
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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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• 제17권6호
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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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• 제23권4호
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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.

• 대한약침학회지
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• 제3권2호
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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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• 제14권4호
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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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• 제31권9호
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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.

• 한국식품영양과학회지
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• 제34권2호
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• pp.176-180
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• 2005

흰쥐를 대상으로 하여 식이 단백질 수준에 따라 칼슘 수준을 달리하여 식이를 공급하여 칼슘 식이효율, 칼슘대사와 관련된 호르몬, 대퇴골의 무게 및 칼슘 함유량, 골밀도를 측정하였다. 실험 식이의 구성은 \circled1 HPNC군-고단백 적정칼슘군(Protein: 400 g/kg diet, calcuim: 0.5%) \circled2 HPLC군-고단백 저칼슘군(Protein: 400 g/kg diet, calcium: 0.1%) \circled3 NPNC군-적정 단백 적정 칼슘군 protein: 200 g/kg diet, calcium: 0.5%) \circled4 NPLC군-적정단백 저칼슘군(protein: 200 g/kg diet, calcium: 0.1%)으로 구별하였다. 실험 종료까지의 체중은 NPLC군에서 가장 많이 증가하였으나, 실험군간의 차이를 나타내지 않았고, 식이 섭취량도 실험군간에 차이를 보이지 않았다. 뇨 칼슘배설량은 고단백군이 적정단백군보다 높은 경향을 나타내었고, HPLC군에서 유의적으로 높은 값을 보였으며 체내 칼슘보유량과 흡수율은 실험군에 따른 차이가 없었다. 뼈형성의 biomarker인 ALP의 활성은 저칼슘 식이군인 NPLC군에서 유의하게 높았고, 고단백 적정칼슘을 섭취한 HPNC군에서 유의적으로 낮았다. 혈액의 PTH 농도는 HPLC군에서 가장 낮게 나타났으며, 소변의 DPD농도는 저칼슘 식이군인 HPLC군과 NPLC군에서 높은 수치로 관찰되었고, HPNC군에서는 유의적으로 낮아졌다. 대퇴골의 건조 전의 습윤무게는 중 100 g당의 무게로 환산했을 때 NPLC군에서 가장 낮았으며 건조 후의 대퇴골의 무게 역시 다른군에 비해 NPLC군에서 가장 낮았다. 대퇴골의 회분 함량은 실험군간의 큰 차이를 나타내지 않았고, 칼슘 함량은 NPLC군과 HPLC군에서 유의하게 낮았다. 대퇴골의 골밀도는 NPNC군에서 가장 높게 나타났으며, NPC군은 가장 낮게 나타났다. 본 연구결과 고단백 저칼슘 식이 섭취시 요중 칼슘 배설량이 가장 많았고, DPD 농도가 다른 군에 비하여 유의적으로 높았으며, 골밀도도 가장 낮게 조사되어 고단백식이 섭취시 칼슘섭취 부족은 칼슘대사에 좋지 못한 결과를 나타냄을 알 수 있었다.이로 볼 때 적절한 단백질과 칼슘 섭취가 골격의 건강을 유지하고 노령화에 따른 골격질환을 예방할 수 있고, 특히 고단백 섭취시에는 칼슘영 양이 부족할 경우 골격 대사를 저해할 수 있으므로 충분한 칼슘 섭 취가 무엇보다도 중요하다고 본다.

• 약학회지
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• 제41권3호
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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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• 제15권2호
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• pp.103-109
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• 1981

Ethanol 투여(投與) 용량(容量)에 따른 혈압(血壓)과 신기능(腎機能)의 변화(變化)를 알아보고자 흰쥐의 복부대동맥(腹部大動脈)에 catheter 를 삽입(揷入)하고 그 다른 끝을 목뒤로 끌어낸 후(後) 1주일(週日)이상 수술(手術)에서 회복(恢復)시킨 다음 실험(實驗)에 사용(使用)하였다. 실험직전(實驗直前)에 방광(膀胱)을 비운 뒤 metabolism cage에 넣어 안정(安靜)시킨 후(後) 60분(分)에 복부대동맥(腹部大動脈)의 catheter를 통(通)하여 평균동맥혈압(平均動脈血壓)(MAP)을 직접(直接) 측정(測定)하고 동맥혈액(動脈血液)과 뇨(尿)를 채취(採取)하였다. 곧 이어 ethanol 은 10 g% (저농도(低濃度)), 또는 30 g% (고농도(高濃度)) 용액(溶液)을, 대조실험(對照實驗)으로는 물을, 체중(體重) 100 g 당(當) 1 ml 씩 각각(各各) 경구(經口) 투여(投與)하였다. 용액투여후(溶液投與後) 3시간(時間)동안 MAP를 측정(測定)하고, 혈액(血液)은 매(每) 시간(時間)마다, 뇨(尿)는 90분(分) 간격(間隔)으로 채취(採取)하여 다음의 결과(結果)를 얻었다. 혈중(血中) ethanol 농도(濃度)는 ethanol 투여후(投與後) 1시간(時間)에 최고치(最高値)를 나타내고 (저농도(低濃度); $105.0{\pm}7.5,$ 고농도(高濃度); $214.7{\pm}20.2\;mg%$), 그후 직선적(直線的)으로 감소(減少)하였다. MAP는 물투여군(投與群)에서는 변화(變化)가 없었으나 ethanol 투여군(投與群)에서는 15분(分)부터 감소(減少)하기 시작(始作)하여 3시간(時間)동안 계속유의(繼續有意)하게 감소(減少)된 상웅(狀熊)를 나타내었다. 뇨량(尿量)은 ethanol 투여군(投與群)에서는 90분(分)동안에 유의(有意)한 증가(增加)를 보여주었고 (저농도(低濃度); $0.88{\pm}0.20{\rightarrow}1.04{\pm}0.22,$ 고농도(高濃度); $0.56{\pm}0.11{\rightarrow}1.35{\pm}0.18\;ml/1.5\;hr$), 180분(分)동안에는 뇨량(尿量)이 ethanol 투여전(投與前)보다 더 낮았다(저농도(低濃度); $0.25{\pm}0.06$, 고농도(高濃度); $0.22{\pm}0.06\;ml/1.5\;hr$). 물투여군(投與群)에서는 뇨량(尿量)이 계속(繼續) 감소(減少)하였다$(0.88{\pm}0.10{\rightarrow}0.59{\pm}0.09{\rightarrow}0.45{\pm}0.09\;ml/1.5\;hr)$. 이상(以上)의 결과(結果)는 ethanol의 혈중농도(血中濃度)가 높을수록 더 심(甚)한 혈압강하작용(血壓降下作用)을 나타내며, ethanol 로 인(因)한 이뇨작용(利尿作用)도 ethanol 량(量)이 증가(增加)함에 따라 뇨량(尿量)도 증가(增加)함을 보여 주었다.

• 대한한의학방제학회지
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• 제16권1호
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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.