• 대한예방의학회:학술대회논문집
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• 대한예방의학회 1996년도 제48차 추계 학술대회 연제집
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• pp.411-412
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• 1996

• Journal of Acupuncture Research
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• 제31권2호
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• pp.39-50
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• 2014

Objectives : This study was designed to evaluate the effects of Tokoro Rhizoma pharmat $KI_{10}$ in nephritis induced by lipopolysaccharide(LPS) in rat. Methods : Rats were divided into 4 groups and 3 groups(LPS, saline, Tokoro Rhizoma pharmacopuncture(TR-P) group) were injected LPS to induce nephritis. TR-P group was treated with TR at $KI_{10}$ three times for a week, saline group with normal saline. To evaluate the effects of TR at $KI_{10}$ on nephritis in rats, white blood cell(WBC), neutrophil in blood, creatinine, cytokine-induced neutrophil chemoattractant-1(CINC-1) in serum and urinary volume, creatinine in urine, renal myeloperoxidase(MPO) were measured and renal tissue was analyzed. Results : TR-P group significantly reduced WBC, neutrophil in blood, creatinine, CINC-1 in serum, creatinine in urine and renal MPO than LPS group. TR-P group increased urinary volume but, not significant. Conclusion : TR at $KI_{10}$ has a therapeutic effect on nephritis in LPS stimulated rat. Therefore, it is suggested that TR at $KI_{10}$ may be an useful therapeutics for nephritis in clinical field after further researches.

• 대한수의학회지
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• 제41권4호
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• pp.583-589
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• 2001

To estalish bio-indices for detection of the development of multistep hepatotumorigenesis, rats were fed water containing 0.01% diethylnitrosamine (DEN) ad libitum for 13-14 weeks. Hepatocellular carcinoma was developed by treatment with DEN, DEN only was able to induce hepatic tumors in rats without any other cocarcinogen. Compared to control group, liver cytosol protein concentration in all treated grous was significantly decreased (p<0.05). From week to week, $20{\alpha}$-hydroxysteroid dehydrogenase ($20{\alpha}$-HSD) activity was increased and the highest activity was observed on the 12th week (p<0.05). In addition, the urine biopterin concentration was also significantly increased compared to control groups (p<0.05) in a time course manner. These results indicated that $20{\alpha}$-HSD activity, urine biopterin and liver cytosol protein concentration might be very useful maker to hepatic tumorigenesis.

• Journal of Acupuncture Research
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• 제31권1호
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• pp.51-60
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• 2014

Objectives : This study aimed to evaluate the effects of Alismatis Rhizoma Herbal-acupuncture( AR-HA) at $KI_{10}$(Umgok) on nephritis induced by lipopolysaccharide(LPS) in rat. Methods : Rats were injected with LPS to induce nephritis. The rats in $KI_{10}$-AR-HA group were treated with AR-HA, $KI_{10}$-NP group with needle prick, $KI_{10}$-saline group with normal saline injection respectively at $KI_{10}$ three times for a week. Several experimental items were performed including measurements of the numbers of RBC, WBC, neutrophil in blood, the levels of creatinine, $TNF-{\alpha}$, CINC-1 in serum, creatinine, total protein in urine, MPO in kidney. Results : Needle prick stimulation at $KI_{10}$ significantly reduced WBC in blood of LPS-stimulated rats. Saline injection at $KI_{10}$ significantly reduced WBC in blood, $TNF-{\alpha}$ in serum, total protein in urine of LPS-stimulated rats. AR-HA at $KI_{10}$ significantly reduced WBC, neutrophil in blood, $TNF-{\alpha}$, CINC-1 in serum, creatinine, total protein in urine of LPS-stimulated rats. Conclusion : AR-HA at $KI_{10}$ has a therapeutic effect on nephritis in LPS-stimulated rat. There may be a synergism between $KI_{10}$(Umgok) stimulation and AR-HA solution.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.272-272
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• 1994

신약개발에 있어서 대사연구는 약효의 species difference, 독성기전, 그리고 in vitro와 in vivo의 약효차이를 이해하는데 매우 중요한 역할을 담당하며 그 연구 영역을 넓혀가고 있다. 본 연구에서는 항혈전제로 개발 가능성이 있는 phosphodiesterase inhibitor인 KR30289의 rat과 rabbit에서 대사 연구를 통하여 약리효과의 상이점을 밝히고져 하였다. Mass analysis를 통하여 urinary 대사체의 구조를 규명한 결과 KR30289를 경구 투여 (1mg/kg)시 hydroxy derivative(M1)와 O-dealkylated derivative(M2)로 변환되어 urine으로 배설되었고 parent compound는 검출되지 않았다 M1과 M2 모두 free form, glucuronide conjugate, 그리고 sulfate conjugate 형태로 검출되었으나 rat과 rabbit 두 종간의 M1과 M2의 비율에서는 커다란 차이점을 보여주었다 rat의 경우 M2가 94% (free form : 14%, glucuronide conjugate 58%. sulfate conjugate, 22%)이었으며 rabbit에서는 M1이 54%로 상대적으로 많이 생성되었다(free form : 11%, glucuronide conjugate : 22%, sulfate conjugate 21%). 이와같이 두종간의 상이한 metabolic profile로 인하여 약리효과의 차이가 유발될수 있다고 추론된다.

• Journal of Acupuncture Research
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• 제29권3호
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• pp.41-53
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• 2012

Objectives : This study was designed to evaluate the effects of Akebiae Lignum herbal acupuncture(AL-HA) at $KI_{10}$ in acute nephritis induced by lipopolysaccharide(LPS) in rat. Methods : Rats were divided into 5 groups and 4 groups were injected LPS to induce acute nephritis. Normal group was normal SD rat, LPS group was injected LPS, AL-HA group was treated with AL-HA at $KI_{10}$ three times for a week, needle prick(NP) group with 26 gauge needle and saline group with normal saline. To evaluate the effects of AL-HA at $KI_{10}$ on acute nephritis in rats, WBC, neutrophil in blood, BUN, TNF-${\alpha}$, CINC-1 in serum and urinary volume, total protein in urine, renal MPO were measured and renal tissue was analyzed. Results : AL-HA group significantly reduced WBC, neutrophil in blood, BUN in serum, total protein in urine and renal MPO. And AL-HA group reduced concentration of neutrophil on glomerulus than LPS group in histological analysis. Conclusions : AL-HA at $KI_{10}$ has a therapeutic effect on acute nephritis in LPS stimulated rat. Therefore, it is suggested that AL-HA at $KI_{10}$ may be an useful therapeutics for acute nephritis in clinical field after further researches.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.243-243
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• 1996

백금착물 항암제 후보물질로서 합성된 KBP31705-Cl27, KBP30603-901을 기존 화합물인 cisplatin 및 carboplatin과 pharmacokinetic profile을 비교 검토하였다. 웅성 Sprague-Dawley rat을 sodium pentobarbital 마취하에서 방광 및 대퇴동맥과 정맥에 polyethylene tubing을 사용하여 catheterization시켰다. Urine 배출이 안정화되었을 때 대퇴정맥내로 cisplatin과 KBP31705-Cl27은 2 mg/kg, carboplatin과 KBP 30603-901은 20mg/kg 용량으로 주사한 후 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120 분에 대퇴동맥으로부터 혈액을 채취하였으며 urine은 약물투여 후 1시간 간격으로 4시간동안 채취하였다. Plasma와 urine중의 platinum농도는 inductively coupled plasma-mass spectrometer를 사용하여 측정하였고, pharmacokinetic parameters는 non-linear least square computer Program인 PCNONLIN을 이용하여 산출되었다. 혈중 platinum농도와 시간의 관계에서 KBP31705-Cl27은 cisplatin과 비교하여 alpha-phase에서 혈중 농도는 낮지만 비슷한 양상을 나타내었고, beta-phase에서는 비교적 느리게 소실됨을 보였다. Urine으로 4시간동안 배출된 platinum양은 각각 투여량의 52, 56%로서 두 약물에서 비슷하였다. 또한 KBP30603-901은 carboplatin과 비교하여 alpha-phase는 거의 비슷한 패턴을 나타내었으나, beta-phase는 훨씬 느리게 감소하여 반감기가 길다는 것을 보여 주었으며 또한 이것은 urine으로 4시간동안 배출된 platinum양이 KBP30603-901의 경우 투여량의 46%로서 carboplatin의 59%보다 적게 배출된다는 data와도 일관됨을 보여주었다. 이상의 결과로 볼 때 KBP30603-901이 다른 백금착물 항암제보다 체내에 머무르는 시간이 길어 혈중에서 보다 오랜 시간동안 머물러 높은 유효농도를 유지할 수 있을 것으로 사료된다.

• 한국환경보건학회지
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• 제40권5호
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• pp.407-412
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• 2014

Objectives: The internal dose of ethyl parabens is important in order to evaluate the risk of this chemical. However, there are little PK model data for parabens to apply this. This experiment attempted PK modeling to ascertain PK values. Methods: Twenty mg/kg ethyl paraben was administered orally to Sprague-Dawley rats at the same point in time. The rats were sacrificed at times 0, 15, 30 and minutes, and 1, 2, 4, 8, 12, 24 hours after oral gavage. Blood and urine were collected and pretreated for analysis. Accuracy, precision and LOD (limit of detection) were calculated for this analysis. Ethyl paraben, detected by HPLC-MS, was applied to PK modeling using Berkeley Madonna. Results: This study showed 100.1-103.7% accuracy, 1.4-3.7% precision and a 1.0 ng/mL limit of detection. Orally administered ethyl paraben reached maximum concentration after 30 minutes of dosing in serum and urine of rats. The concentrations were 2,354 ng/mL in serum and 386,000 ng/mL in urine samples. These peak concentrations were excreted after one hour of intubation over 12 hours. For the pharmacokinetic parameters of ethyl paraben revealed using Berkeley Madonna, the absorption rate was 5.539/hour, the excretion rate was 0.048/hour, the half-life was 14.441 hours and AUC was 481,186 ng hour/mL. Conclusion: Orally administered ethyl paraben was absorbed rapidly in rats and excreted in urine. This chemical, ethyl paraben, accumulated in the body but was excreted over 12 hours after dosing.

• 한국동물위생학회지
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• 제22권1호
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• pp.61-70
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• 1999

This study is concerned with assessment of diethylnitrosamine(DEN) induced liver cell carcinogenesis by measurement of changes preceding the development of neoplasms. Therefore, it was undertaken to investigate the changes of liver-specific enzyme activities in rats (Sprague-Dawley) by ad libitum feeding of DEN. And also, as another objective index in urine, the level of urinary biopterin was measured by high performance liquid chromatography(HPLC) method. The results were as follows ; 1. Minor behavioral change, brittleness of hair and decreased amount of water and diet intake were observed in rats 7 weeks after DEN administration. 2. The body and liver weights were significantly(p<0.05) decreased in rats 11 weeks after DEN administration. 3. The ratio of liver weight to body weight was rather stable and not significantly decreased in the all treatment groups. 4. The liver specific enzyme activities(AST, ALT,$\gamma$-GTP) were significantly(p<0.05) increased in all treatment groups compared to control group. 5. Compared to normal level, urine biopterin level was significantly (p<0.05) increased in all treatment groups(p<0.05). In conclusion, this result confirmed that the DEN was one of the potent hepatocarcinogens. In experimental model of rats exposed to DEN, the results indicated that values of liver specific enzyme activities(AST, ALT, $\gamma$-GTP) and urine biopterin level could be useful complementary tumor indices.

• Toxicological Research
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• 제12권1호
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• pp.47-52
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• 1996

The renal toxicity of the extract of Polygalae Radix was investigated in rats. Rats were treated with 3.5 mg/Kg of the extract, i.p., for 7 days. Changes in consumatory behavior, 24 hour-urine and the activities of urinary enzymes were determined during the administration of the extract. Significant decrease in body weight and food consumption and increase in 24 hour-urine volume were observed during the administration. However, the quantity of total creatinine in urine was decreased significantly. Those indicate that subacute treatment with the extract might induce diuresis and the ditiresis might be due to the decrease in water reabsorption. In the activities of urinary enzymes, the activities of alanine aminopejotidase (AAP) and gamma-glutamyl transpeptidase (GGT) were increased 4.3 and 3.5 times and then returned to the control. The activity of N-acetyl-${\beta}$-D-glucosaminidase (NAG) was increased 7.2 times and then decreased slowly. But, it was significantly higher than that of the control evea after the last administration. The activity of factate dehydrogenase (LDH) was increased continuozlsly during the treatment. It showed 32 times higher than the control. These results suggested that the extract of Polygalae Radix had toxic effect on kidney. Furthermore, the result suggested that the subacute administration of the extract induced resistance against the toxicity of Polygalae Radix.