• Title/Summary/Keyword: Approximate lethal dose

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Acute and 28-Day Subacute Toxicity Studies of Hexane Extracts of the Roots of Lithospermum erythrorhizon in Sprague-Dawley Rats

  • Han, Chung-Tack;Kim, Myoung-Jun;Moon, Seol-Hee;Jeon, Yu-Rim;Hwang, Jae-Sik;Nam, Chunja;Park, Chong-Woo;Lee, Sun-Ho;Na, Jae-Bum;Park, Chan-Sung;Park, Hee-Won;Lee, Jung-Min;Jang, Ho-Song;Park, Sun-Hee;Han, Kyoung-Goo;Choi, Young Whan;Lee, Hye-Yeong;Kang, Jong-Koo
    • Toxicological Research
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    • v.31 no.4
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    • pp.403-414
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    • 2015
  • Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes.

Honey Bee Venom (Apis mellifera) Contains Anticoagulation Factors and Increases the Blood-clotting Time

  • Zolfagharian, Hossein;Mohajeri, Mohammad;Babaie, Mahdi
    • Journal of Pharmacopuncture
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    • v.18 no.4
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    • pp.7-11
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    • 2015
  • Objectives: Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Methods: Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Results: Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations $(SDs)={\pm}0.71$; however, clotting was observed in the control group 13.8 s, $SDs={\pm}0.52$. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The $LD_{50}$ of the crude BV was found to be $177.8{\mu}g/mouse$. Conclusion: BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase $A_2(PLA_2)$ and melittin, and that can increase the blood clotting times in vitro.

Single Dose Oral Toxicity of Schisandrae Semen Essential Oil in ICR Mice (ICR 마우스를 이용한 오미자 종자 정유의 단회경구투여 독성시험)

  • Han, Min Ho;Kim, Joo Wan;Kim, Ki Young;Kim, Sung Goo;Yu, Gyeng Jin;Cho, Yong Bok;Hwang, Hye Jin;Kim, Byung Woo;Kim, Cheol Min;Choi, Yung Hyun
    • Journal of Life Science
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    • v.24 no.2
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    • pp.191-195
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    • 2014
  • Essential oils extracted or purified from various plants have shown various beneficial effects. Seed parts of Schizandra chinensis Baillon (Schisandrae Semen) have been used as a traditional medicine for thousands of years in parts of Asia, including Korea, China, and Japan. However, the pharmacological mechanisms of essential oils purified from S. fructus (S. chinensis Baillon) remain largely unresolved. The aim of this study was to investigate the safety of Schisandrae Semen essential oil (SSeo) by a single- dose toxicity study in mice. SSeo was orally administered at a dose of 5,000 mg/kg in ICR mice. All animals were sacrificed after 14 days of treatment. After a single administration, mortality, clinical signs, body weight changes, and gross pathological findings were observed for 14 days. We also measured parameters of organ weight, clinical chemistry, and hematology. No toxicological change related to the test substance or mortality was observed after administration of a single oral dose of SSeo. There were no adverse effects on clinical signs, body weight, or organ weight and no gross pathological findings in any treatment group. The clinical chemistry and hematological parameters were within the normal ranges except total bilirubin. Therefore, the approximate lethal dose for oral administration of SSeo in mice was considered to be over 5,000 mg/kg. The results on the single-dose toxicity of SSeo indicate that it is not possible to reach oral dose levels related to death or dose levels with any harmful side effects.

Acute and Subchronic Toxicity of Gamma-Irradiated Orange (감마선 조사 오렌지의 급성 및 아만성 독성 평가)

  • Jung, Da-Woon;Huang, Yu-Hua;Choi, Geun-Pyo;Kang, Il-Jun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.9
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    • pp.1286-1294
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    • 2015
  • The acute and subchronic toxicity of 1 kGy gamma-irradiated orange was evaluated in ICR mice. For acute toxicity, groups of 30 male and 30 female ICR mice were orally administered 1 kGy gamma-irradiated orange (0, 1,000, and 2,000 mg/kg). The mortality, clinical sign, body weight changes, and necropsy findings of ICR mice were observed for 14 days. No significant changes in body weight or abnormal gross findings were observed in relation to 1 kGy gamma-irradiated orange. Hematological and serum biochemical parameters were within normal ranges. According to the results, 1 kGy gamma-irradiated orange had no special toxic effects in male and female ICR mice at 2,000 mg/kg. For subchronic toxicity, groups of 36 male and 36 female ICR mice were given a diet of 1 kGy gamma-irradiated orange for 13 weeks (control, non-irradiated, and irradiated imported orange). During the experimental period, mortality, clinical signs, body weight change, food consumption, organ weight, and histopathological examination did not show any changes in comparison to the control group. Several hematological and serum biochemical parameters showed statistically significant changes, but these changes were within normal range. These results indicate that 1 kGy gamma-irradiated orange did not cause any toxic effects in male and female ICR mice and therefore can be considered as safe.