• 대한수의학회지
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• 제32권1호
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• pp.35-39
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• 1992

Sulfamethazine(SMZ)은 수의임상에서 감염증 치료 및 예방목적으로 많이 사용되고 있을 뿐 아니라 가축의 생산성 향상을 위해 남용되고 있는 주요한 항균제의 하나이다. SMZ의 생체내 대사 및 약물동태학적 특성은 동물의 종차에 따라 상이함이 잘 알려져 있으나 주요 실험동물 및 경제동물인 토끼에서 조사된 바는 매우 드물다. 한편 성차에 따른 약물대사의 차이는 rat를 비롯한 여러 동물에서 인정되고 있는데 대체로 숫컷이 암컷에 비해 대사능이 활발한 것으로 알려져 있다. 그러나 산양에서의 SMZ의 대사는 오히려 암컷이 더 활발하다는 보고도 있어, 여러 동물종에서 일률적으로 성차에 따른 약물대사를 설명할 수가 없다. 초식성의 습성을 가지고 있는 토끼에 있어 성차에 따른 SMZ의 대사 및 약물동태학적 특성이 다른 초식성 동물인 산양의 경우와 동일한 경향을 보이는지는 매우 흥미 있다할 것이다. New Zealand White 토끼에 SMZ을 이정맥에 35mg/kg를 주사한 후 미리 정해진 시간에 수거된 혈장 및 뇨(24시간)를 HPLC를 이용하여 분석하여 아래와 같은 약물동태학 및 대사적 특성을 얻었다. 1. 토끼에서의 SMZ의 주요 대사경로는 아세틸화$(N_4AcSMZ)$이었다. 두개의 수산화 대사산물(50HSMZ, $6CH_2OHSMZ$)도 생성되어 수산화 경로가 있음을 확인하였으나 양적인 관심에서 주요하지 않았다. 2. 토끼에서의 SMZ의 각 대사산물의 생성은 암수간의 성차에 따른 차이가 인정되지 않았다. 3. SMZ을 토끼의 이정맥에 투여(35mg/kg)하였을 때의 약물동태학적 특성은 1구1차 지수형 배설형태로 설명이 가능하였으며 암수에 따른 성차가 인정되지 않았다. 4. SMZ는 신속하게 $N_4AcSMZ$로 대사되었으며, $N_4AcSMZ$의 체외배설은 SMZ에 비해 매우 느렸으며 성차에 따른 배설속도의 차이를 인정할 수 없었다.

• 동의생리병리학회지
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• 제18권3호
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• pp.868-873
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• 2004

Renal dysfunction could be developed as the secondary disease of liver cirrhosis. Delayed or suppresed lipid peroxidation by the treatment with physiological active substances could be explained as the antioxidative and protective effect in tissue damage. In this study, we investigated an antioxidative effect and renal function improvement of Hovenia dulcis in liver fibrosis(cirrhosis) induced rats. The female Sprague-Dawley rats (180∼210 g) were divided into 3 groups (Normal, AC: CCl₄ mixture treated group, AC-HV: CCl₄ mixture+ Hovenia dulcis treated group) and renal damage was developed by CCl₄ mixture administration in 4 weeks (0.8 ㎖/rat). The tissue of kidney and liver and sera were used for quantitative measurement of enzyme activity, MDA and Hyp. The histological change and gene expression of collagen α1(III) mRNA and a1(IV) mRNA were observed by Masson's trichrome staining and RT-PCR. As a result, the clinical biochemical parameters of liver function (AST and ALT) in sera of AC-HV group showed significantly 46.4% and 104.8% lower (p<0.005), and the level of ALP and BUN as the parameter of protein urine and azotemia showed 17.8 % and 25.8 % lower than in AC group. In AC-HV group, the concentration of MDA in kidney and liver was decreased significantly 15.8% and 21.3% when compared with AC group (p<0.01 -0.005). The content of Hyp in kidney of AC-HV group is merely higher than in AC group, in contrast to liver tissue. The expression of collagen α1(III) mRNA and collagen α1(IV) mRNA was decreased in AC, but both of collagen mRNA in normal and AC-HV group expressed fast similar. More massive lipid droplets, thicker collagen fiber bundles in portal triads and more formation of portal central septum were observed in the liver of AC group than in AC-HV group. In conclusion, CCl₄ mixture intoxication could be developed not only liver fibrosis(cirrhosis) but also renal dysfunction by the massive lipid peroxidation and suppression of interstitial collagen and basement membrane collagen synthesis. And the water extract of Hovenia dulcis may be possessed the antioxidative and protective effect and improvement of kidney function in renal dysfunction induced rats.

• 동아시아식생활학회지
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• 제15권1호
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• pp.20-28
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• 2005

The dietary effect of water extracts of Liriopis tuber(WELT) in the diabetic SD-rats on the level of blood sugar and serum cholesterol was investigated. The experimental plots divided into normal group(N), diabetic control(DC), 5% WELT-group(WELT-I) and 10% WELT-group (WELT-II). Each group was fed for 6 weeks, then continuously fed for 1 more week after streptozotocin injection. The loss of the body weight fed for one week after induction of the diabetes was 2.2～6.3% in the WELT-I and -II groups, but it was 18.6% in the DC-group. There was no significant difference in the feed intakes after diabetes induction between N-group and WELT-group, while it was significantly increased in DC-group. The feed efficiency ratios before diabetes induction were 1.70 in WELT-I group, 1.53～1.59 in the N, DC and WELT-II group, while the ratios after diabetes induction were 0.92 in DC-group, 1.51～1.83 in the N, WELT-I and -II group. While the amounts of water intakes for one week after diabetes induction was 625.4 mL in the DC-group, and it were 364.3～371.1 mL in the WELT-groups showing no significant difference with N-group. The excretion amounts of urine were 431.96 mL in DC-group for one week after diabetes induction, and it was 182～192.84 mL in WELT-groups. The ratios of liver weight against body weight were 2.74% in N-group, 2.93～2.96% in WELT-groups, but it was 4.01% in DC-group. The level of blood glucose in WELT-groups fed for one week after diabetes induction were 136.8～138.6 mg/dL showing no significant difference with N-group, but it was 357.8 mg/dL in DC-group. The level of serum triacylglycerol and serum total cholesterol were 93.8 and 68.7 mg/dL in N-group, 120.1 and 101.6 mg/dL in DC-group, 97.4～100.6 and 60.8～67.7 mg/dL in WELT-groups, respectively, showing no significant difference between N-group and WELT-groups. HDL-cholesterol/total cholesterol ratio were 0.63 in N-group, 0.57～0.67 in WELT -groups, which was significantly higher than that of DC-group(p<0.05). Atherogenic index were 0.58 in N-group, 0.49～0.74 in WELT-groups, but it was 1.32 in DC-group. The above results suggest that the WELT diets may have both preventive and curing effects against the diabetes.

• Biomolecules & Therapeutics
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• 제5권3호
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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.

• 농약과학회지
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• 제14권4호
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• pp.490-498
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• 2010

살균제 isotianol의 독성을 평가하고 일일섭취허용량을 설정하기 위하여 급성독성시험 등 시험성적서를 검토하였다. Isotianil은 소변과 대변을 통해 빠르게 대사되었다. 급성경구독성은 저독성이었으며 피부자극, 안점막자극성은 없는 것으로 나타났다. 피부감작성은 약한 감작성으로 판단되었으며, 유전독성은 없었다. 랫드와 개 만성독성시험 결과 간의 무게, 혈액학 및 임상생화학적 변화가 관찰되었다. 또한 생식독성과 기형독성에는 영향이 없었다. Isotianil은 12개월 만성독성시험의 최대무작용량이 2.83 mg/kg/bw/day로 가장 민감하였고, 안전계수 100을 적용하여 일일섭취허용량을 0.028 mg/kg/bw/day로 설정하였다.

• Toxicological Research
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• 제25권3호
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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.

• 한국식품영양과학회지
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• 제33권7호
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• pp.1119-1125
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• 2004

콩 식이섬유로부터 제조한 헤미셀룰로즈가 streptozotocin으로 유발한 당뇨쥐의 혈당과 혈청콜레스테롤함량에 미치는 영향을 조사하였다. 실험군은 셀룰로즈군(대조군), 헤미셀룰로즈 0.5% 식이군(H-1군), 헤미셀룰로즈 1% 식이군(H-2군)으로 나누어 6주간 사육한 후 당뇨를 유발시키고 계속해서 1주간 사육하였다. 당뇨유발에 따른 식이섭취량과 체중증가량 및 식이효율은 H-2식이군이 대조군과 H-1군에서 보다 높은 값을 나타낸 반면 음용수 섭취량은 H-2군에서 낮았다. 간장의 무게는 H-2군이 대조군과 H-1군에 비하여 유의적으로 낮았다. 혈당은 대조군에서는 212.8 mg/dL, H-1 군에서는 160.5 mg/dL, H-2군에서 는 141.0 mg/dL으로 H-2군은 대조군의 66%수준이었으며 뇨당은 대조군 0.97 mg/dL, H-1군 0.53 mg/dL, H-2군 0.35 mg/dL로 H-1군은 대조군의 55%, H-2군은 대조군의 36%로 헤미셀룰로즈 식 이군이 대조군에 비하여 유의적으로 낮았다. 혈청내 중성지질의 함량은 식이에 따른 유의적 인 차이는 보이지 않았으나 혈청 총콜레스테롤 함량은 대조군에서 101.6 mg/dL, 식이군에서는 73.8∼78.4 mgidL로 유의적으로 낮았으며, 혈청 HDL-콜레스테롤 함량은 모든 실험군에서 39.8∼44.7 mg/dL 범위로 비슷한 수치를 나타내었다. HTR과 동맥경화지수는 대조군에서는 각각 0.44 및 1.27로 나타났으나 헤미셀룰로즈 식이군에서는 각각 0.54 및 0.46∼0.85로 대조군보다 낮았다. 이상의 결과, 콩 식이섬유로부터 추출한 헤미셀룰로즈는 항당뇨효과가 높음을 나타내었다.

• 대한의생명과학회지
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• 제12권1호
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• pp.23-27
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• 2006

The rate of metallothionein synthesis on cadmium-poisoned rats reflects the level of toxicity, and also it reduces the toxicity which is caused by the uptake of cadmium. Chlorella supplementation in the diets of the cadmium-poisoned rats decreased the concentration of cadmium in blood and urine compared with the control group. Although the liver and kidneys of rats are major target organs of cadmium and coherence of metallothionein and cadmium, no previous study has determined the correlation between the rate of metallothionein synthesis in the liver and kidneys of rats and dietary supplementation of chlorella with cadmium uptake. This study analyzed total metallothionein level on the tissue of the liver and kidneys, the concentration of cadmium bound to the metallothionein, and the total concentration of cadmium on the tissue of the liver and kidneys after dietary supplementation with 1%, 5%, and 10% dried chlorella and 40 ppm of cadmium to 46 male SD rats (mean weight: $150\pm20\;g$) for 4 weeks. According to the data analysis of the total rate of metallothionein synthesis in the liver and kidneys, the group of SD rats on the supplementation with 1% chlorella and 40 ppm of cadmium showed a rate of $93.2\pm8.9\;ng/g$, a significant decrease of 58.8% compared to that of the control group of SD rats on the supplementation with cadmium only, which showed a rate of $227.3\pm32.5 ng/g$ (P=0.0001). In contrast, no significant difference was observed through the changing of chlorella concentrations between 5% and 10% chlorella supplementation with cadmium. The group supplemented with 1% or greater chlorella levels represented a greater decrease in the total cadmium concentration of the kidney and liver tissues, the amount of total metallothionein synthesis, the amount of metallothionein with binding to cadmium, and the concentration of free cadmium without binding to metallothionein. Consequently, the supplementation of 1% and 5% chlorella was effective in reducing the synthesis of metallothionein for cadmium uptake, but increased the rate of binding of cadmium to metallothionein.

• 동의생리병리학회지
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• 제18권2호
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• pp.474-483
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• 2004

To know the effects between Cd inhalation toxicity and extract of Radix Achyranthis Bidentatae, 4 rat groups were exposed to Cd aerosol in air using whole-body inhalation exposure for 6 hours/day, 5 days/week, and 4 weeks. Cd concentration in air was 1.03㎎/㎥ and mass median diameter(MMD) was 1.69㎛. 3 different dose intraperitoneal injections of extract of Radix Achyranthis Bidentatae to 3 inhalation exposure groups was done for 4 weeks and the results were as follows: The highest body weight gain for 4 weeks and food intake per day were from inhalation exposure group I and the highest lung and liver weight were also from inhalation exposure group I. The highest kidney weight was from inhalation exposure group III. The lowest Cd content in lung was 33.49㎍/g from inhalation exposure group I. The lowest Cd concentration in blood was 9.36㎍/㎗ from inhalation exposure control. Cd concentrations of 40.02㎍/g in liver and 69.18㎍/g in kidney were the lowest from inhalation exposure group I and III, respectively. The lowest Cd concentration in liver was 21.08㎍/g from inhalation exposure group III and The lowest Cd concentration in kidney was 15.78㎍/g from inhalation exposure group II. For weekly Cd concentration in urine, the value of the fourth week from inhalation exposure group III was the highest. For weekly Cd concentration in feces, the value of the first week from inhalation exposure group III was the highest. The highest metallothionein concentration in lung was 53.42 ㎍/g from inhalation exposure group III and the highest metallothionein concentration in liver was 188.18㎍/g from inhalation exposure group III. The highest metallothionein concentration in kidney was 143.92㎍/g from inhalation exposure group III. The highest Hct, Hb, and WBC values were from inhalation exposure group II and the highest RBC value was from inhalation exposure group III.

• 동의생리병리학회지
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• 제16권6호
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• pp.1243-1252
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• 2002

To experiment the effects between cadmium inhalation toxicity and extracts of Folium Mori, rat inhalation exposure groups were exposed to cadmium aerosol in air by whole-body inhalation exposure for 6 hours/day, 5 days/week, and 4 weeks. Cadmium concentration in the air of cadmium aerosol was 1.02㎎/㎥ and mass median diameter(MMD) was 1.40μm. Intraperitoneal injection of extracts of Folium Mori to inhalation exposure groups was done for 4 weeks and the results were as follows: The highest body weight gain for 4 weeks and food intake per day were 126.39g/4 weeks and 19.18g/day from inhalation exposure group III, respectively. The highest lung and liver weight were 1.27g and 8.19g from inhalation exposure group II, respectively. The highest kidney weight was 1.805g from inhalation exposure control. The lowest cadmium content in lung was 86.39μg/g from inhalation exposure group III. The lowest cadmium concentration in blood was 7.12㎍/㎗ from inhalation exposure group III. Cadmium concentrations of 40.02㎍/g in liver and 69.18㎍/g in kidney were the lowest from inhalation exposure group I and III, respectively. For weekly cadmium concentration in urine, the value of the fourth week from inhalation exposure group III was the highest, 3.12㎍/㎖. For weekly cadmium concentration in feces, the value of the fourth week from inhalation exposure group III was the highest, 2.67 ㎍/g. The highest metallothionein concentration in lung was 74.65㎍/g from inhalation exposure group III and the highest metallothionein concentration in liver was 386.84㎍/g from inhalation exposure group II. The highest metallothionein concentration in kidney was 236.17 ㎍/g from inhalation exposure group II.