• 동의생리병리학회지
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• 제24권2호
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• pp.249-257
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• 2010

Crataegii Fructus is commonly used as a improving digestion, removing retention of food, promoting blood circulation and resolving blood stasis agent in East Asia. Cadmium (Cd) is widely distributed in the environment due to its use in industry. An exposure to Cd causes dysuria, polyuria, chest pain, hepatic and renal tubular diseases. The liver is the most important target organ when considering Cd-induced toxicity because Cd primarily accumulates in the liver. This study investigated the protective effect of Crataegii Fructus water extract against cadmium ($CdCl_2$, Cd)-induced liver toxicity in H4IIE cells, a rat hepatocyte-derived cell line and in rats. Cell viability was significantly reduced in Cd-treated H4IIE cells in a time and concentration-dependent manner. However, Crataegii Fructus water extract (CFE) protected the cells from Cd-induced cytotoxicity via inhibition of PARP cleavage. To induce acute toxicity in rats, Cd (4 mg/kg body weight) was dissolved in normal saline and intravenously injected into rats. The rats then received either a vehicle or silymarin (as a positive control) or CFE (50, 100 mg/kg/day) for 3 days, and were subsequently exposed to a single injection of Cd. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were significantly increased by Cd treatment. In contrast, pretreatment with CFE reduced ALT, AST and LDH. In histopathological analysis, CFE reduced the hepatic degenerative regions and the number of degenerative hepatocytes. These are considered as direct evidences that Crataegii Fructus has favorable inhibitory effects on the Cd-intoxicated liver damages. The efficacy of Crataegii Fructus shows slight lower than that of silymarin in the present study.

• 대한약침학회지
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• 제21권2호
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• pp.104-111
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• 2018

Objective:This study is to evaluate both the single-dose intravenous injection toxicity and the approximate lethal dose of Water-soluble Danggui Pharmacopuncture (WDP) in Sprague-Dawley (SD) rats. Methods: Toxicity experiments were conducted at Good Laboratory Practice (GLP) laboratory in Biotoxtech Co., according to the regulations of GLP. WDP injection of dose 0.125, 0.25, and 0.5 mL/animal were experimental groups and normal saline injection group was control group. WDP and normal saline were injected once to 6- week old 5 male and 5 female SD rats at the tail veins at approximately 2 mL/min. During 14 days after the injection, general symptoms were observed and weight were measured. After the observation period, hematological and blood biochemical examination, macroscopic autopsy, topical resistance test at the injection area were performed. Results: RThe WDP 0.5 mL/animal injection group in 4 cases of male rats and all cases of female rats showed hematuria 30 minutes after the administration. However, after 1 hour, no more abnormal general symptoms were observed. The WDP did not affect weight, hematological and blood biochemical examination, macroscopic autopsy, and topical resistance test at the injection area. Conclusion: WDP single dose intravenous injection results showed that WDP have no toxic effects and a lethal dose of WDP should be over 0.5 mL/animal in male and female rats under the study condition. So WDP may be safe.

• Journal of Ginseng Research
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• 제35권1호
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• pp.39-44
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• 2011

We studied the acute oral toxicity of black ginseng (BG) produced by heat process in rats. Single acute BG extract doses of 0, 5, 10, and 15 g/kg dissolved in saline were administered by oral gavage and the animals were kept under observation for 14 days. The single administration of BG extract up to 15 g/kg did not produce mortality, behavioral change or abnormal clinical signs in the rats. These results indicated that the oral $LD_{50}$ of the BG extract in the rats is higher than 15 g/kg. Compared to the control group, no treatment-related biologically significant effects of BG extract were noted in the measurements of the body weight or food intake. At the end of the period, the biochemical parameters and hematological parameters were analyzed in the plasma and blood. A histopathological examination of the liver and kidney was also conducted. Only the blood nitrogen urea and potassium levels in the biochemical indices showed significant differences at 10 and 15 g/kg doses of BG extract compared to the control group. These changes were not considered to be due to the toxicity. None of the other clinical chemistry parameters were affected. Therefore, these results indicate that the BG by heat processing is virtually nontoxic.

• Toxicological Research
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• 제30권3호
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• pp.205-210
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• 2014

Didecyldimethylammonium chloride (DDAC) is used for various purposes, such as a fungicide for coolants, an antiseptic for wood, and disinfectant for cleaning. Despite the increasing likelihood of DDAC inhalation, available data on its toxicity from inhalation are scarce. Therefore, this study was aimed at confirming the toxicity of DDAC after inhalation exposure for 2 wk. Male Sprague-Dawley rats were exposed to approximately $0.15mg/m^3$, $0.6mg/m^3$, and $3.6mg/m^3$ DDAC aerosols in whole-body exposure chambers. After DDAC exposure for 2 wk, effects of DDAC on body weight, blood, bronchoalveolar lavage (BAL), and the lungs were verified. The mass median aerodynamic diameter of DDAC aerosols was $1.86{\mu}m$ and the geometric standard deviation was 2.75. The concentrations of DDAC aerosols for the low, medium, and high groups were $0.15{\pm}0.15mg/m^3$, $0.58{\pm}0.40mg/m^3$, and $3.63{\pm}1.56mg/m^3$, respectively. Body weight gain was significantly influenced by DDAC exposure. In the high group, a body weight decrease of 2.6 g was observed, whereas a 25.8 g increase was observed in the normal control group after the first 3 days. The low and medium groups showed 23.3 g and 20.4 g increases, respectively, after the first 3 days. Decreases in body weight were recovered during the next 4 days. In contrast, no changes were noted in hematological and blood biochemistry parameters after DDAC exposure. Furthermore, only mild effects were observed on bronchoalveolar cell differentiation counts and cell damage parameters in the BAL fluids of the medium and high groups. Although inflammatory cell infiltration and interstitial pneumonia were partially observed, fibrosis was not found in the lungs of the medium and high groups. In conclusion, body weight gain and the lungs were mainly affected by DDAC exposure. The no-observed-adverse-effect level (NOAEL) for DDAC was determined as $0.15mg/m^3$.

• 대한약침학회지
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• 제22권3호
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• pp.147-153
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• 2019

Objectives: Many studies have been reported the efficacy of intravenous lipid emulsion (ILE) as an antidote on acute lipophilic drug toxicity. Clozapine, highly lipophilic dibenzodiazepine neuroleptics, is an important medication in the schizophrenia therapy regimen. Acute intoxication with antipsychotics is one of the main reasons for the referral of poisoned patients to the hospital. We expected that ILE could be used for the therapy of acute clozapine intoxicated patients. Methods: We used two groups of consisting of six male rats. Both groups received a toxic dose of clozapine (40 mg/kg) intravenously, via the tail vein. After 15 minutes, they were treated with intravenous infusion of 18.6 mg/kg normal saline (NS group), or 18.6 mg/kg ILE 20% (ILE group). We evaluated blood pressure (BP) and heart rate by power lab apparatus through the tail artery, ataxia by a rat rotary circle, seizure scores and death in multiple times after starting clozapine administration. For biochemical and pathological evaluations the samples of tissue and blood were taken. Results: Our results demonstrated that ILE 20% could return hypotension-induced clozapine better than normal saline. Furthermore, ataxia and seizure have rectified more rapidly and deaths reduced. Clozapine administration causes pancreatitis and lung injury but fat emulsion did not show an optimal effect on tissue damages caused by clozapine toxicity. Conclusion: In conclusion, ILE can remove toxic signs of clozapine same as other lipophilic medicines, however, clinical uses of ILE for this intention requires more appraisement to determine the precise implication and safety.

• Korean Journal of Acupuncture
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• 제34권4호
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• pp.241-250
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• 2017

Objectives : This study was performed to examine the toxicity of Aconitum ciliare Decaisne pharmacopuncture(ADP). Methods : The toxicity was evaluated for lethal dose for 50 percent kill(LD50), single dose and repeated dose for 4 weeks. Toxic symptoms, weight measurement, hematological test, blood biochemical test, visual examination and weight measurement of major organs and histopathological test were observed for 4 weeks. Dose of 300, 600, 1,200, 2,400, 3,600, 4,800, 6,000, 7,200 mg/kg in the LD50 experiment, 300, 600, 1,200 mg/kg/day in the single experiment, 150, 300, 600 mg/kg/day in 4 weeks experiments were injected into BALB/c mice. The ADP was injected into ST36 of the right leg. Normal saline solution of same volume was used for control group. In 24 hours after the last treatment, blood samples were taken after anesthesia by inhalation of ethyl ether. After that, the BALB/c mice were euthanized. Their heart, lungs, kidneys, liver and reproductive organs were removed and weighed. Histopathological evaluation was also performed. Results : ADP's LD50 was measured at 6,000 mg/kg. In both single and repeated dose toxicity test, no BALB/c mouse died during the experiments. ADP treatment for 4 weeks did not show any significant changes in toxic symptoms, weight measurement, hematological test, blood biochemical test, visual examination and weight measurement of major organs and histopathological test. Conclusions : As a result, ADP's LD50 was 6,000 mg/kg and repeated dose at a concentration of 600 mg/kg or less is considered to be not harmful for clinical treatment.

• 한국가스학회지
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• 제21권1호
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• pp.6-17
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• 2017

본 연구는 3-methylpentane에 대한 흡입유해성을 평가하여 국제연합에서 정하는 화학물질의 분류 및 표지에 관한 세계조화시스템(Globally harmonized system, GHS)지침 및 고용노동부고시 제2013-37호에 따른 3-methylpentane의 화학물질 분류 표시 자료를 생산하기 위하여 OECD 화학물질 시험가이드라인 아급성흡입독성시험 TG 412(Subacute inhalation toxicity) 시험법에 따라 수행하였다. 본 연구를 위하여 6주령의 랫드(Rat)를 도입하여 1주간 순화시킨 후 암수 각각 대조군 5마리, 저농도군(284 ppm) 5마리, 중농도군(1,135 ppm) 5마리, 고농도군(4,540 ppm) 5마리 등으로 군을 구성하여 일일 6시간, 주 5일, 4주 동안 시험물질을 랫드에 전신으로 노출시켰다. 시험물질 노출을 종료하고 2주 후 시험동물을 희생하여 시험물질에 의한 시험동물의 영향을 평가하였다. 사료섭취량 변화, 체중 변화, 임상관찰, 혈액검사, 부검 소견, 장기무게 측정, 조직병리검사 등 모든 시험결과에서 시험물질에 의한 영향은 나타나지 않아 3-methylpentane의 무유해영향농도는 암수 모두 4,540 ppm이상으로 판단되어 세계조화시스템(GHS) 지침 및 고용노동부고시 제2013-37호(화학물질의 분류 표시 및 물질안전보건에 관한 기준)의 특정표적장기독성(반복노출) 구분 표시 물질에 해당하지 않은 물질로 판단되었다.

• Nutrition Research and Practice
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• 제12권6호
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• pp.535-540
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• 2018

BACKGROUND/OBJECTIVES: Propolis has a rich source of bioactive compounds and has renal and hepatic protective properties. The purpose of this study was to investigate the beneficial effect of hydro-ethanolic extract of propolis against paracetamol-induced liver damage and impairment of kidney function, as well as hematological changes in rats. MATERIALS/METHODS: Six groups of rats were used; the first group was served as a control; the second and third groups were treated by propolis extract at a dose of 50 and 100 mg/kg.B.WT. respectively; the fourth group was treated by paracetamol (200 mg/kg.B.WT.); the fifth group was treated by propolis (50 mg/kg.B.WT.) for eight days and then received similar dose of propolis for following seven days with paracetamol at a dose of 200 mg/kg.B.WT. daily for the seven days; and the sixth group was treated with propolis (100 mg/kg.B.WT.) for eight days and then received similar dose of propolis for following seven days with paracetamol at a dose of 200 mg/kg.B.WT. daily for the seven days. All the animals were treated for a period of 15 days. At the end of the experimental period, blood samples were collected for measurement of the liver enzymes, serum albumin, protein and creatinine, blood urea nitrogen, hematological parameters, and urine volume, protein and albumin. RESULTS: Paracetamol over dose significantly lowered hemoglobin, serum total protein, albumin, and uric acid, while it significantly increased blood creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, white blood cells, and platelet count as compared to the control. However, these alterations were significantly attenuated by the use of propolis extract and the effect was dose dependent. Interestingly, propolis prevented paracetamol induced proteinuria, low hemoglobin and body weight loss. CONCLUSIONS: Propolis significantly prevented paracetamol induced renal, hepatic and hematological toxicity and might be useful in the management of liver and renal diseases particularly proteinuria.

• Journal of Veterinary Science
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• 제24권3호
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• pp.43.1-43.8
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• 2023

Background: Meloxicam is used widely for exotic animal analgesia, but its toxicity in common raptor species in Thailand is unclear. Objectives: This study evaluated the single-dose effect of intramuscular meloxicam in common raptor species in Thailand for short-term and long-term periods. Methods: Twenty-two raptors were administered a single 1 mg/kg dose of meloxicam individually via intramuscular injection. The following were evaluated: clinical appearance, body weight, body condition score, body temperature, fecal appearance, complete blood cell count, and biochemistry panel before (day 0) and after the injection (1, 7, and 30 days). The collected samples were categorized into three groups: Brahminy kite (Haliastur indus) (n = 10), adult Barn owl (Tyto javanica) (n = 4), and juvenile Barn owl (n = 8). Results: None of the raptors in the study groups showed any abnormalities. The hematological profiles were significantly different in the short-term period (day 1 and day 7). The creatinine, aspartate aminotransferase, and creatinine kinase increased in several groups. On the other hand, the packed cell volume decreased in the Brahminy kite and juvenile Barn owl groups. According to the findings, an intramuscular injection of 1 mg/kg meloxicam affected the blood biochemistry panel of the muscle, but the affected raptors recovered within one week. Conclusions: An intramuscular injection of meloxicam at a single 1 mg/kg dose in Brahminy kites and Barn owls was not associated with the morbidity, hepatotoxicity, gastrointestinal toxicity, and nephrotoxicity in the short- and long-term periods.

• International Journal of Industrial Entomology and Biomaterials
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• 제32권1호
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• pp.12-25
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• 2016

Recently, research investment in the improvement of food safety as a food source and specializing of nutritional source of edible insects is being actively conducted. Cricket especially has been attracting considerable interest in entomophagy; however, research on the safety assessment of cricket is limited. This study investigated the effects of cricket ethanol extract when orally administrated in Sprague-Dawley rats. Here, we performed a 4 wk repeated oral dose toxicity test in Sprague-Dawley rats following the Organization for Economic Cooperation and Development test guidelines 407 under Good Laboratory Practice regulation. Rats were randomly allocated 4 groups: vehicle control, 250, 500, 1,000 mg/kg test groups and administrated based on body weight for 28 d. The animals were observed for mortalities and clinical signs, body weight changes, food and water consumption. At the end of treatment period, blood and urine were collected and analyzed. Subsequently, the animals were sacrificed and subjected to gross pathological examination and organ weight measurement. The organs were preserved for histopathological examination. The results showed that there were no systemic toxicological effects related with the cricket ethanol extract in the 4 wk oral repeated dose toxicity study. It is considered that NOAEL of cricket ethanol extract is greater than 1,000 mg/kg/d and there was no target organ detected.