• 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.

• Toxicological Research
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• 제18권4호
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• pp.397-400
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• 2002

This study was carried out to investigate the acute toxicity of G. bimaculatus in Sprague-Dawley rats. G. bimaculatus was administered orally at doses of 8, 40, 200, 1000 and 5000 mg/kg. in this study, number of deaths, clinical sign, body weights, and pathological examination were investigated for 14 days after administration of G. bimaculatus. The results indicate that G. bimaculatus did not show any toxic effect in rats and oral $LD_{50}$ value was over 5000 mg/kg in Sprague-Dawley rats.

• Biomolecules & Therapeutics
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• 제5권1호
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• pp.12-22
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• 1997

Intravenous and oral acute toxicity tests in ICR mice and SD rats and percutaneous acute toxicity tests in SD rats and NZW rabbits were conducted to evaluate the toxicity of DA-5018 and DA-5018 cream, respectively Clinical signs observed in mice and rats after the administration of DA-5018 were similar regardless of administration route. The observed clinical signs were jumping, wild running, lacrimation, ataxia, reddening of extremities and ears, ventral or lateral recumbency, respiratory distress, cyanosis, convulsion and death. Pulmonary enlargement and hemorrhage were observed in the animals died immediately after the dosing of DA-5018. At terminal necropsy, pulmonary enlargement and hemorrhage, corneal opacity and focal scabbing and depilation around nose were seen. LD$_{50}$ Values of DA-5018 are 11.5 mg/kg (mice, male), 12.6 mg/kg (mice, female), 88.3 mg/kg (rat, male) and 73.2 mg/kg (rat, female) in oral toxicity tests and 11.0 mg/kg (mice, male), 18.7 mg/kg (mice, female), 0.12 mg/kg (rat, male) and 0.32 mg/kg (rat, female) in i.v. toxicity tests. In the percutaneous acute toxicity tests of DA-5018 cream, no deaths occured in all the tested groups during 14-day observation period. There were also no abnormalities in the general conditions, body weight changes and on necropsy findings in all groups. LD$_{50}$ values of 0.1 ~0.9% DA-5018 creams in male and female rats and rabbits are >2000 mg/kg./kg.

• 한국지역사회생활과학회지
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• 제26권3호
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• pp.511-522
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• 2015

This study investigates the acute and repeated-dose oral toxicity of crude antifungal compounds produced by Lactobacillus plantarum AF1 (Lb. plantarum AF1) and Lactobacillus plantarum HD1 (Lb. plantarum HD1) in male and female Sprague Dawley rats. In the acute toxicity study, crude antifungal compounds (500, 1,000, and 2,000 mg/kg) did not reduce mortality or produce significant changes in general behaviors or the gross appearance of external and internal organs. In the repeated-dose toxicity study, crude antifungal compounds were administered orally to rats at doses of 500, 1,000, and 2,000 mg/kg daily for 28 days. There were no test-article-related deaths, abnormal clinical signs, or body weight changes. In addition, there were no significant differences between groups treated with crude antifungal compounds and the control group in their organ weight, hematological and serum biochemical parameters, or any other factors. These results suggest that the acute or repeated-dose oral administration of crude antifungal compounds produced by Lb. plantarum AF1 plus Lb. plantarum HD1 is not toxic in male and female rats.

• 생약학회지
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• 제39권4호
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• pp.352-356
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• 2008

Acute toxicity of standardized extract of Salvia miltiorrhiza Bunge was examined using male and female ICR mice. Mice were treated with standardized extract the intragastrically at 5 mg/kg, 50 mg/kg, 500 mg/kg or 2,000 mg/kg and observed for two weeks. At the doses used, no mortality or abnormal clinical signs in animals were shown during at the observation period. Also there was no difference in net body weight gain, gross pathological findings at the terminal sacrifice among the groups mice treated with different doses of the test substance. The results suggested that acute oral toxicity of standardized extract of S. miltiorrhiza in mice is very low at the conditions employed in this study.

• Toxicological Research
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• 제14권3호
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• pp.385-391
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• 1998

The study was carried out to evaluate the acute toxicity of enrofloxacin-colistin combination via a single oral(p.o.)and intravenous(i.v.) administration in ICR mice. All procedures of the test were performed by the established regulation of Korean National Institute of Safety Research (1994. 4.14). The maximal dose of oral and intravenous routes was 5,000mg/kg and 90mg/kg, consisting with each 6 groups including control of male and female, respectively. As the results, $LD_{50}$m}'s of the combinations showed 3,075mg/kg (f)and 2,564mg/kg(m) after oral administrations, together with 48mg/kg(f) and 40mg/kg(m) after intravenous administration. These facts indicated that acute toxicitiy of enrofloxacin-colistin combination were different depending on the administration routes and sexes in ICR mice. In conclusion, the route of enrofloxacin-colistin combination must not choose as i.v. route administration in terms of acute toxicity based on $LD_{50}$.

• Toxicological Research
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• 제21권1호
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• pp.63-70
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• 2005

Gami-Honghwa-Tang (KH-19), a herbal prescription for reducing the side effect of radiotherapy, is composed of eight crude herbs such as Rehmanniae Radix Preparata, Angelicae Gigantis Radix, Cnidii Rhizoma, Paeoniae Radix, Corni Fructus, Moutan Cortex Radicis, Lycii Fructus, Carthami Flos, and Glycyrrhizae Radix. In this study, marker substances in KH-19 were analyzed by high performance liquid chromatography-diode array detector (HPLC-DAD) and safety evaluation of standardized KH-19 was evaluated by good laboratory practices (GLP) guideline of Korea Food and Drug Administration. HPLC-DAD was employed to determine the quantities and the qualities of several marker substances such as 5-hydroxymethyl-2-furaldehyde (5-HMF), paeonol, loganin, paeoniflorin, glycyrrhizin, and decursin in the KH-19. In acute oral toxicity study on rat, transient inhibition of body weight was shown, but change in general symptom was not detected. No dead animal was observed up to 5,000 mg/kg in both male and female animals. In acute oral toxicity study on Beagle dog, transient vomiting, diarrhea, anorexia, and body weight reduction were observed, However, no dead animal was observed up to 2,000 mg/kg in both male and female animals.

• 한국수산과학회지
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• 제47권4호
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• pp.356-362
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• 2014

Phlorotannins, the major constituent in brown algae, possess various biological activities; however, there is little information their toxicological effects. To assess the safety of phlorotannins, we investigated the acute oral toxicity of a high-purity phlorotannin preparation (PRT; total phlorotannin content 90%) in beagle dogs. Six beagle dogs (3 males, 3 females) were assigned randomly to three experimental groups. PRT was administered at oral doses of 250, 500, and 750 mg/kg by capsule. Vomiting by male and female beagles was observed with 500 and 750 mg/kg on the first day. In addition, one beagle given 750 mg/kg had soft stool and diarrhea on days 3 and 13. No deaths or abnormal clinical signs were observed during the experiment. All groups showed similar body weight gain and food consumption. Our acute toxicity study showed that PRT did not cause any toxicological effects in beagle dogs.

• Toxicological Research
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• 제20권4호
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• pp.359-363
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• 2004

This study provides more information about the potential toxicological risk of Bacillus sp. A9184 isolated from soybean paste. The evaluation was based on the guidelines of acute oral toxicity/pathogenicity for microbial pesticide and was to get more comprehensive understanding on the acute toxicity of the potential probiotic in Sprgue-Dawley rats. No dead animal was observed in rats after single oral administration with bacteria ($10^8$ CFU per animal). There were neither no treatment-related changes in clinical signs, nor changes in body weight and body temperature as com-pared with the untreated group. All tested animal showed the increase in body weight with time. The results obtained in this study suggest that the potential probiotic, Bacillus sp. A9184, is non-toxic for rat.

• Biomolecules & Therapeutics
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• 제9권1호
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• pp.46-50
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• 2001

The current study was performed to determine the acute oral toxicity of a crude extract of sanghwang mushroom (Phellinus linteus), in SD rats. 5 rats of each sex were orally treated with a single dose of extract of sanghwang mushroom at doses of 0, 500, 1,000, 2,000 mg/kg, respectively. After the treatment, clinical signs and body weight change, the food and water consumption were observed for 14 days. All animals survived during the study and did not show any clinical signs. Body weight gain showed no significant difference between the control and treated rats. However, body weight gain delayed in high dose group (2,000 mg/kg) on day 1~3 after administration. Another 5 rats of each sex were orally treated with a single dose of extract of sanghwang mushroom at dosages 4,000, 5,000 mg/kg respectively, but all animals survived during the study and did not show any clinical signs. It is suggested that LD$_{50}$ of extract of sanghwang mushroom by oral administration was estimated to be over 5,000 mg/kg in both sexes of rats.s.