• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2004년도 KSOT/KEMS Fall Annual Meeting
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• pp.37-40
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• 2004

• 한국독성학회:학술대회논문집
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• 한국독성학회 2004년도 KSOT/KEMS fall annual meeting
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• pp.37-40
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• 2004

• Journal of Ginseng Research
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• 제44권5호
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• pp.717-724
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• 2020

Background: Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. Methods: Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride-induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. Results: The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca²⁺/calmodulin-dependent protein kinase II. Conclusion: Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.

• 대한약침학회지
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• 제17권1호
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• pp.51-58
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• 2014

Objectives: This study was performed to analyze single-dose intramuscular toxicity of Guseonwangdo-go glucose pharmacopuncture. Methods: Eighty six-week-old Sprague-Dawley rats were divided into two large groups of forty rats; Guseonwangdo-go glucose 5% and Guseonwangdo-go glucose 20% groups. Each group was sub-divided into four smaller groups of five males and five females, with the following dosages of pharmacopuncture being administered by intramuscular (IM) injection in each group: group 1 (G1, control group): 1.0 mL of normal saline solution, group 2 (G2, low-dose group): 0.1 mL, group 3 (G3, mid-dose group): 0.5 mL, and group 4 (G4, high-dose group): 1.0 mL. Results: No mortalities or clinical signs were observed in any group. Also, no significant changes in body weights or in hematological/biochemical analyses were observed between the control and the experimental groups during necropsy or histopathology. Conclusion: The above findings suggest that the lethal dose of Guseonwangdo-go glucose 5% and 20% pharmacopuncture administered via IM injection is more than 1.0 mL per animal in both male and female rats. Further studies on the repeated-dose toxicity of Guseonwangdo-go glucose should be conducted to yield more concrete data.

• 대한한방내과학회지
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• 제26권2호
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• pp.369-378
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• 2005

An herbal water extract of Bojungikkeehapdaechilkitang(BDT) was prepared to test it for single-dose and repeated-dose toxicity, genotoxicity and reproductive toxicity, and to obtain a 50% lethal dose$(LD_{50})$, approximated lethal dose(ALD), and approximated target organs for BDT. The extract was tested on female and male ICR mice according to KFDA Guideline 1999-61 at doasge level of 2000, 1000, 500, 250 and 125mg/kg/10mL In this study, clinical signs, mortalities and gross findings of principal organs were observed for 14 days of single dosing, and afterwards in some cases. The ALD and $LD_{50}$ of BDT extract obtained in this study was>2000mg/kg for both male and female ICR mice. Also, any possible digestive toxicity of BDT extract was found to be above 1000mg/kg in both male and female ICR mice. The results of this study strongly suggest that BDT extract has no toxic effect at dosage level below 500mg/kg.

• 한국식품영양과학회지
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• 제45권10호
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• pp.1406-1413
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• 2016

상지추출물의 독성을 복귀돌연변이, 단회투여 및 반복투여 독성 등 다각적으로 적용하여 평가하였다. 상지추출물의 복귀돌연변이 실험을 Salmonella Typhimurium의 히스티딘 요구성 균주 4종과 Escherichia coli의 트립토판 요구성 균주 1종을 이용하여 대사활성계 적용 및 비적용 하에서 Ames test를 실시하였다. 대사활성계 유무에 상관없이 $5,000{\mu}g/plate$의 처리 농도까지 복귀돌연변이 콜로니 수는 증가되지 않았으므로 상지추출물은 복귀돌연변이를 유발하지 않는 것으로 판단하였다. SD rats 암수에 1,250, 2,500 및 5,000 mg/kg의 농도로 단회 경구투여 하고 14일 동안 일반증상, 운동성, 식이섭취량, 사망 여부 및 체중 변화를 조사한 결과, 사망동물은 관찰되지 않았으며 대조군과 비교하여 실험동물의 암수 모두에서 시험물질 투여에 따른 일반적인 증상변화는 나타나지 않았다. 대조군과 시험군은 모두 정상적인 체중 증가가 관찰되었고 대조군과 비교하여 상지추출물 투여군의 유의적인 체중 변화는 나타나지 않았으며, $LD_{50}$은 암수 모두 5,000 mg/kg 이상인 것으로 판단하였다. 또한, 상지추출물을 500, 1,000 및 2,000 mg/kg/d의 용량으로 28일간 반복 경구투여 하면서 실험동물의 일반증상, 사망동물의 유무, 체중 변화, 식이섭취량, 혈액학적 및 혈액생화학적 변화, 부검 후 육안적 검사를 통한 병변의 유무를 관찰하였다. 시험기간 동안 암수 모든 군에서 반복 투여로 인한 사망동물이 없었으며 정상적인 체중 증가가 나타났다. 대조군과 비교하여 상지추출물의 투여에 따른 체중 변화는 통계학적으로 유의성이 없었으며 암수 모두 대조군과 비교하여 식이섭취량의 차이 및 유의할만한 일반증상도 관찰되지 않았다. 시험물질의 투여에 따른 장기 무게, 혈액학적 분석 결과 및 혈액생화학적 분석 결과 등에서도 독성 및 이상소견이 발견되지 않았다.

• Toxicological Research
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• 제24권3호
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• pp.219-225
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• 2008

A screening study of the acute toxicity of organic arsenics such as arsenobetaine and arsenocholine, a product of arsenic methylation metabolite, and inorganic arsenic was carried out to examine hematological and serum biochemical parameters in cynomolgus monkeys(Macaca fascicularis). We found soft and liquid feces, and vomiting in all treated groups with inorganic and organic arsenics. The monkeys in inorganic arsenic-treated group showed a significant increase in vomiting frequency compared with those in three organic arsenics-treated groups. These results suggest that inorganic arsenic might be more toxic than three other organic arsenics tested. The monkeys in inorganic arsenic-treated group showed a decrease in platelet and an increase in monocyte on day 4 and the monkeys in arsenocholine-treated group showed an increase in reticulocyte percentage on day 8. The monkeys in inorganic-treated group also showed decreases in AST and ALT values and the monkeys in arsenobetaine-treated group showed a decrease in AST value and an increase in T-CHO value. However, these hematological and biochemical changes were within the physiological ranges, showing that the single dose of inorganic and organic arsenics did not affect at least hematological and serum biochemical parameters. The present study of toxicity with single dose of arsenics provides valuable indicators for longer term study of toxicity of repeated doses of arsenics in primates.

• 한국식품과학회지
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• 제46권2호
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• pp.249-255
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• 2014

본 연구에서는 사용된 가시오가피 영지버섯 발효물과 가시오가피 상황버섯 발효물에 대한 열수추출물을 최고 2 g/kg의 농도로 단회 투여한 SD-rats에 체중 변화, 임상증상 등에서 어떠한 독성도 관찰할 수 없었으며, 1 g/kg 이하의 농도로 4주간 반복 투여한 SD-rats에서도 체중변화, 임상증상, 장기 무게, 혈액학적 성상, 혈액생화학적 성상 등에서 어떠한 독성과 비정상적인 소견을 관찰할 수 없었다. 따라서, 본 연구의 결과로 볼 때 가시오가피 영지버섯 발효물 열수추출물(FM-5111)과 가시오가피 상황버섯 발효물 열수추출물(FM-5131)은 본 연구에서 사용한 농도 내에서의 안전성을 확인할 수 있었다. 황 함유 아미노산의 결핍은 여러 가지 간질환 등의 증상을 야기한다(27). 또한, Choi와 Ahn(28)은 오가피 부위별 50% (v/v) 메탄올 추출액의 전자공여능은 줄기 추출물에서 90.21%, 뿌리 추출물에서 85.71%로 높은 활성을 보고하여 오가피의 항산화능을 규명하였다. 따라서, 본 연구에 사용된 시료 또한 항산화능과 같은 기능성을 가질것으로 사료되며, 추가 연구로 아미노산 분석을 통해 황 함유 아미노산의 함량 변화를 분석하고 간 기능 개선 효능을 평가하여 안전성이 확보된 기능성 식품소재 개발 연구를 진행할 계획이다.

• 약학회지
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• 제43권2호
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• pp.180-197
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• 1999

Acute and subacute oral toxicity of $HELIKIT^{TM}$ ($^{13}C-urea$) were carried out in Sprague-Dawley rats of both sex. The toxicity of $HELIKIT^{TM}$ was compared with urea($^{12}C-urea$ which is used for control). In acute toxicity studies, we daily examined number of deaths, clinical signs, body weights and pathological examination for 14 days after single oral administration of HELIKIT or urea($^{12}C-urea$) at a dose of 5000 mg/kg. The subacute oral toxicity was investigated in Sprague-Dawley rats treated with $HELIKIT^{TM}$ at a dose of 40, 200 and 1,000 mg/kg/day or $^{12}C-urea$ at a dose of 1,000 mg/kg/day for 4 weeks. In acute toxicity studies, $HELIKIT^{TM}$ and urea did not show any toxic effect in rats and oral LD50 value was over 5,000 mg/kg rats. In subacute toxicity studies, no death occured and no drug-related changes were found in clinical observations; body weight, food consumption, opthalmoscopy. auditory test, urinalysis, hematology, blood chemistry, gross pathological examination or organ weight between $HELIKIT^{TM}$, urea and control groups. In histopathological examinations, the slight thickening of mucosa of the limiting ridge in the stomach was noted in the animals treated with $HELIKIT^{TM}$ at a dose of 1,000 mg/kg/day and also the changes in urea group at a dose of 1,000 mg/kg/day was found, but all of these changes in the changes in ures group at a dose of 1,000 mg/kg/days was found, but all of these changes in the stomach regressed after withdrawal of the test article for 2 weeks and reversibility of the effect was revealed. These results indicate that the non toxic dose level of $HELIKIT^{TM}$ was 1,000 mg/kg/day in the 4 weeks-repeated dose study, suggesting that the substitution of $^{13}C$ for carbon in urea molecule has no effect on the toxicity of urea and changes in stomach are reversible.

• 동의생리병리학회지
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• 제22권2호
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• pp.296-301
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• 2008

The purpose of this study was to examine to observe single and four weeks repeated toxicity in mice of Bangpung-galgeun-tang (BGT). We investigated to ascertain safety and toxicity of BGT, we divided into single and four weeks repeated administration test. In single test, three groups were administrated different dosages and routes (2 g/kg/i.p., 4 g/kg/i.p. and 15 g/kg/p.o.) of BGT, and in four weeks repeated test, 0.8 g/kg BGT was administrated. Control groups were administrated with only saline according to on Korean Food and Drug Administration, respectively. We observed attentively motality, abnormal clinical sign, body weight change, organ weight, AST and ALT of mice after BGT administration. During toxicity experiment period, there was no difference in body weight change, organ weight, AST and ALT among different dose groups. Death were found 3 mice from day 2 to day 3 in single test i.p. group. (2 g/kg, 4 g/kg). Several individuals of single test i.p. group were observed that decreased locomotor activity, exophthalmos, bloodshot eyes, loss of eyesight and so on in early period after administration. But there was no difference in clinical signs among p.o. group. These results indicate that BGT have inhibition effects on allergy and suggest that no observable effect level of the test orally administration was considered to be more than 2 g/kg in mice under the conditions employed in this study.