• Title/Summary/Keyword: single dose oral toxicity

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Antiarrhythmic effects of ginsenoside Rg2 on calcium chloride-induced arrhythmias without oral toxicity

  • Gou, Dongxia;Pei, Xuejing;Wang, Jiao;Wang, Yue;Hu, Chenxing;Song, Chengcheng;Cui, Sisi;Zhou, Yifa
    • Journal of Ginseng Research
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    • v.44 no.5
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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.

Safety Evaluation of Ethanol Extract of Inulae Flos : Single-dose Oral Toxicity Study in Mice (선복화 에탄올 추출물의 급성 독성 연구)

  • Kwon, Da Hye;Kim, Min Young;Hwangbo, Hyun;Ji, Seon Yeong;Park, Cheol;Choi, Yung Hyun;Hong, Su Hyun
    • Herbal Formula Science
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    • v.28 no.2
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    • pp.169-177
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    • 2020
  • Objectives : This experiment was designed to assess the single oral toxicity of Ethanol Extract Inulae Flos (IF) ethanol extracts. IF is one of the important herbs to remove phlegmy which is the viscous turbid pathological product that can accumulate in the body, causing a variety of diseases. Nevertheless, there has been a lack of research on the pharmacology toxicity of IF. Methods : In this study, IF was orally administered to 5 weeks ICR mice as an oral dose of 2,000 or 3,000 or 5,000 mg/kg. The condition of the mice was observed for 14 days and their weights were measured every two days. Results : None of the mice died for 14 days. The abnormal clinical symptoms and anatomical signs of toxicity were not found in any treatment groups. The gain of net body weight was observed. There was also no significant difference in the organ weight. The serum biochemistry and hematological analysis showed a decrease in BUN, red blood cells, white blood cells and platelets although within the normal ranges. Conclusions : These results suggest that the 50% lethal dose of IF is more than 5,000 mg/kg. This could be thought that IF is a safe drug without acute toxicity and side effects. However, IF showed some weight loss and change in blood test, so it will need to be careful when using it for high doses.

Single-Dose Toxicity and Four Week Repeated-Dose Toxicity Study on Tensolin-F® (3,9-diferuloyl-6-oxopterocarpen) (Tensolin-F® (3,9-diferuloyl-6-oxopterocarpen)의 단회 독성시험 및 4주 반복투여 독성시험)

  • Kim, Keun-Su;Park, Sung-Min;Lee, Nam-Jin;Pyo, Hyeong-Bae;Chai, Hee-Yul;Jung, Yu-Ri;Lin, Chun-Mai;Kim, Sun-Hee;Lee, Hye-Young;Kang, Jong-Koo
    • Toxicological Research
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    • v.23 no.4
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    • pp.405-413
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    • 2007
  • This study was to investigate single and repeated-dose toxicities of Tensolin-$F^{(R)}$, an anti-wrinkle agent, in Sprague-Dawley (SD) rats or ICR mice. In single-dose oral toxicity study, the test materials were administered once by gavage to male and female SD rats at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and Tensolin-$F^{(R)}$ treated group. Therefore, the approximate lethal dose of Tensolin-$F^{(R)}$ was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test material was administered once daily by gavage to male and female ICR mice at dose levels of 0, 25, 50 and 100 mg/kg/day for 4-weeks. In the results, no abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, necropsy findings, histopathological findings. In hematological analysis, there was a trend of increase in reticulocyte at male 25 mg/kg, although such changes were in normal ranges. On the other hand, there was a trend of decrease in hemoglobin at female 50, 100 mg/kg, such changes were in normal ranges. In addition, serum biochemical parameters including sodium, BUN and chloride increased at 25, 50 and 100 mg/kg. Relative organ weights of right testis, brain, lung and left epididymis were increased in 100 mg/kg groups of male rats in contrast to not change in female groups. However, these changes of relative organ weights, hematological and serum biochemical parameters were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, 4-week repeated oral dose of Tensolin-$F^{(R)}$ to ICR mice did not cause apparent toxicological change at the dose of 25, 50, 100 mg/kg body weight. Consequently the no-observed-adverse-effect level (NOAEL) for Tensolin-$F^{(R)}$ in ICR mice following gavage for at least 4-week is higher than 100 mg/kg/day.

Single Oral Dose Toxicity Test of Kong-Jin-Dan, a Polyherbal Formula in ICR Mice

  • Park, Mee-Yeon;Choi, Hae-Yun;Kim, Jong-Dae;Lee, Hyeung-Sik;Ku, Sae-Kwang
    • Biomolecules & Therapeutics
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    • v.15 no.4
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    • pp.245-251
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    • 2007
  • The object of this study was to evaluate the single dose toxicity of Kong-Jin-Dan (KJD), a polyherbal formula in male and female mice. KJD was administered to female and male ICR mice as an oral dose of 2000, 1000 and 500 mg/kg (body wt.) according to the recommendation of KFDA Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy, organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, and changes in the body and organ weight except for increases of lymphoid organ weights in KJD-dosing groups. These increases of lymphoid organ weights considered that related to the immune modulate effect of KJD not toxicological signs. In addition, no KJD-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for some sporadic accidental findings. The results obtained in this study suggest that the KJD does not cause any toxicological signs. The $LD_{50}$ and approximate LD of KJD extracts in both female and male mice were considered as over 2000 mg/kg.

Single Oral Toxicity Study of 3-Methoxy-6-Allylthiopyridazine in Rats

  • Jung, Ki-Hwa
    • Biomolecules & Therapeutics
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    • v.13 no.2
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    • pp.123-126
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    • 2005
  • The single dose toxicity of 3-methoxy-6-allylthiopyridazine (K-6) was studied with Sprague-Dawley rats. K-6 was administered orally with dosages of 4.0, 3.0, 1.5, 1.0, 0.5, 0.25 and 0.1 g/kg to the rats. We observed daily the number of death, clinical signs, body weights and gross findings. All rats (6) were dead within a day after administration when doses of 4.0and 3.0 g/kg were administered. When dose of 2.0 g/kg was administered, 2 rats among 3 rats were dead. Any significant toxicity below 1.5g/kg of K6 was not observed when the different doses of 1.5, 1.0, 0.5, 0.25 and 0.1 g/kg were administered to 6 rats respectively.

Single Oral Dose Toxicity Study of Water Extracts of Polygalae Radix in ICR Mice

  • Kang, Byung Hoon;Ku, Sae Kwang;Seo, Bu Il;Roh, Seong Soo;Park, Soo Jin;Park, Ji Ha
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.27 no.4
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    • pp.453-459
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    • 2013
  • The objective of this study was to evaluate the single oral dose toxicity of Polygalae Radix (PR) in male and female mice. PR extract (yield = 18.6%) was administered to ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines (2009-116, 2009). Animals were monitored for the mortality and the changes in body weight, clinical signs and gross observation during 14 days after dosing. Upon necropsy, organ weight and histopathology of 14 principal organs were examined. It was observed that there were no mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs related to PR extract up to 2,000 mg/kg. Therefore, 50% lethal dose ($LD_{50}$) and approximate LD of PR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg the limited dosages recommended by KFDA Guidelines, respectively.

Mouse Single Oral Dose Toxicity Test of Bupleuri Radix Aqueous Extracts

  • Kim, Kyung-Hu;Gam, Cheol-Ou;Choi, Seong-Hun;Ku, Sae-Kwang
    • Toxicological Research
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    • v.28 no.1
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    • pp.11-18
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    • 2012
  • The aim of this study was to evaluate the single oral dose toxicity of Bupleuri Radix (BR) aqueous extracts, it has been traditionally used as anti-inflammatory agent, in male and female mice. BR extracts (yield = 16.52%) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principal organs were examined. As the results, no BR extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs were detected up to 2,000 mg/kg in both female and male mice, except for soft feces and related body weight decrease detected in male mice treated with 2,000 mg/kg. Therefore, $LD_{50}$ (50% lethal dose) and approximate LD of BR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg, respectively. Although it was also observed that the possibilities of digestive disorders, like soft feces when administered over 2,000 mg/kg of BR extracts in the present study, these possibilities of digestive disorders can be disregard in clinical use because they are transient in the highest dosages male only.

Mouse Single Oral Dose Toxicity Test of Red Koji Fermented Scutellariae Radix Aqueous Extracts (홍국 발효 황금의 마우스 단회 경구투여 독성시험)

  • Park, Jae-Chan;Choi, Hae-Yun;Kim, Jong-Dae
    • Herbal Formula Science
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    • v.21 no.1
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    • pp.186-199
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    • 2013
  • Objectives : The objectives of this study was to obtain acute information (single oral dose toxicity) of Red-Koji (Monascus purpureus 12002) Fermented Scutellariae Radix Aqueous Extracts (fSR), has been traditionally used in Korean medicine for treating various diseases including inflammatory diseases. Methods : In order to observe the 50% lethal dose (LD50), approximate lethal dosage (ALD) and target organs, fSR powders were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight.). The mortality and changes on body weight, clinical signs and gross observation were monitored during 14days after single oral treatment of fSR with organ weights and histopathological observations of 12 types of principle organs. Results : After single oral treatment of fSR, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents, on the body and organ weights, clinical signs, gross and histopathological observations, except for some accidental findings. Conclusions : The results obtained in this study suggest that the LD50 and ALD of fSR in both female and male mice after single oral treatment were considered as over 2,000 mg/kg because no mortalities were detected up to 2,000 mg/kg and can be safety used in clinics.

Assessment of the Single Oral dose Toxicity of Glycyrrhiza New Variety Extract in Sprague-Dawley Rats (Sprague-Dawley rats에서 감초 신품종 추출물의 단회투여 독성 평가)

  • Dong-Gu Kim;Jeonghoon Lee;Wonnam Kim;yo-Jin An;Jong-Hyun Lee;Jaeki Chang;Sa-Haeng Kang;Young-Jae Song;Yong-Deok Jeon;Jong-Sik Jin
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2021.04a
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    • pp.65-66
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    • 2021
  • Glycyrrhiza species (Licorice) are one of the most commonly used medicinal plants in Asian countries such as China, India and Korea. It has been traditionally used to treat many disease including cough, cold, asthma, fatigue, gastritis and respiratory tract infections. Glycyrrhiza new variety, Wongam (WG), have been developed by Korea Rural Development Administration and revealed several pharmacological effects. However, limited data are available on the potential adverse effects of the WG. Here, we evaluated the general toxicity of the WG extract through single oral dose toxicity study in Sprague-Dawley rats. After single oral dose administration, there was no mortality up to 5000 mg/kg during experiment period. In addition, there was no clinical signs including body weight change, gross findings and necropsy findings up to 5000 mg/kg during experiment period. To conclude, the no-observed-adverse-effect level (NOAEL) of WG was higher than 5000 mg/kg and no target organs were identified in male and female Sprague-Dawley rats.

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Single Dose Toxicity Study of Socheongryong-tang in Sprague-Dawley Rats (Sprague-Dawley 랫드를 이용한 소청룡탕의 단회투여독성시험)

  • Lee, Chul-Won;An, Won-Gun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.2
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    • pp.242-245
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    • 2011
  • Socheongryong-tang has been used for the treatment of inflammatory allergic diseases such as allergic rhinitis and bronchial asthma in Asian countries. This study was conducted to investigate the safety of Socheongryong-tang in rats. The safety of this tang on acute toxicity was evaluated by single dose toxicity study. Rats were orally administrated in a single dose of 0 and 2000 mg/kg (limited dose) Socheongryong-tang. There were 7 rats in each groups. All animals were sacrificed after 14 days of treatment. After single administration, mortality, clinlcal signs, body weight changes and gross pathological findings were observed for 14 days. Three parameters were tested: organ weight measurement, clinical chemistry, and hematology. In this study with rats, Socheongryong-tang treatment did not show any acute toxicity. No mortality was noted for 14 days of treatment. There were no adverse effects on clinical signs, body weight, organ eight and gross pathological findings at all treatment groups. The clinical chemistry parameters attesting to liver and kidney functions as well as the hematological parameters were within the normal ranges. From single dose toxicity study with rats, it is considered that $LD_{50}$ of Socheongryong-tang is over 2000 mg/kg in oral administration. This finding of the safety on single dose toxicity study of Socheongryong-tang are expected to strengthen the position of Socheongryong-tang as nontoxic medicine.