• 한국환경보건학회지
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• 제44권2호
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• pp.153-159
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• 2018

Objectives: This study was carried out to determine $LD_{50}$ of benzo[a]pyrene to decide the possibility to designate them as toxic substance on the Act on the Registration and Evaluation, etc. of Chemical Substances, and to suggest that they should be managed in what level on the Chemical Control Act. Methods: Based on the result of a preliminary study, 300 mg/kg was set as the middle dose. A highest dose of 2,000 mg/kg and a lowest dose of 50 mg/kg were selected based on the OECD TG 423. Benzo[a]pyrene was orally administered once to female and male SD rats at dose levels of 50, 300, 2,000 mg/kg (body weight). All animals were monitored daily for clinical signs and mortality over 14 days. Also testicular spermatid count, motility and etc. were examined as well. Results: Under the condition of this experiment, $LD_{50}$ of benzo[a]pyrene was assumed to be >2,000 mg/kg. In the lesion according to autopsy, there were no specific symptoms in the control and experimental groups. At 2,000 mg/kg, a decrease in the sperm motility was observed. Benzo[a]pyrene should be designated to be toxic substance as the material assumed to be reproduction-toxicity on the Act on the Registration and Evaluation, etc. of Chemicals. Therefore we should abide by legal procedures determined by Chemicals Control Act in treating it. Conclusion: Considering the significant result that sperm motility in the experimental group was inferior to that in the reference group, we suggest that benzo[a]pyrene be designated as a toxic substance.

• 대한본초학회지
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• 제28권2호
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• pp.17-23
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• 2013

Objectives : To investigate the hepatoprotective effect of Gardeniae Fructus (Ga) and Glycine semen preparatum (Gl) aqueous extract against D-galactosamine (D-GalN, 300mg/kg body weight) was administered to the male Sprague Dawley (SD) rats. Materials and Methods : The study was carried out on male SD rats (age matched, weight $250{\pm}10$ g). Experimental groups (Exp) divided four : Normal group (Nor) was administered saline, Control (Con) group was only received D-GalN (300 mg/kg) intraperitoneally. Exp was orally administered Ga (200 mg/kg; Ga group), Gl (700 mg/kg; Gl group), and Chizadochi-Tang (200 mg/kg+700 mg/kg, GG group) after D-GalN treatment during 14 days (n=6). Results : D-GalN administration induced hepatotoxicity in rats which was manifested by increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) but decreased total cholesterol (HDL C) and triglyceride (TG). The serum TG concentrations were significantly increased ($^{\sharp}p$ <0.05) in the Ga group compared with Con. AST and ALP activities were significantly decreased ($^{\sharp}p$ <0.05) in the all experimental groups compared with Con. ALT activities were significantly decreased ($^{\sharp}p$ <0.05) in the Ga group compared with Con. LDH activities were significantly decreased ($^{\sharp}p$ <0.05) in the GG group compared with Con. On the light microscopic study, a number of vacuole were observed in the Con, but decreased in experimental groups. Conclusion : Ga aqueous extract and Chizadochi-Tang extract possesses hepatoprotective potential, thus validating its use in alleviating toxic effects of D-GalN.

• Biomolecules & Therapeutics
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• 제20권2호
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• pp.220-225
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• 2012

To develop a ginseng product possessing an efficacy for diabetes, ginseng radix ethanol extract was treated with pectinase and obtained the GINST. In the present study, we evaluate the beneficial effect of GINST on high fat diet (HFD)-induced hyperglycemia and hyperlipidemia and action mechanism(s) in ICR mice. The mice were randomly divided into five groups: regular diet group (RD), high fat diet group (HFD), HFD plus GINST at 75 mg/kg (GINST75), 150 mg/kg (GINST150), and 300 mg/kg (GINST300). Oral glucose tolerance test reveals that GINST improves the glucose tolerance after glucose challenge. Fasting plasma glucose and insulin levels were decreased by 4.3% and 4.2% in GINST75, 10.9% and 20.0% in GINST150, and 19.6% and 20.9% in GINST300 compared to those in HFD control group. Insulin resistance indices were also markedly decreased by 8.2% in GINST75, 28.7% in GINST150, and 36.4% in GINST300, compared to the HFD control group. Plasma triglyceride, total cholesterol and non-esterified fatty acid levels in the GINST300 group were decreased by 13.5%, 22.7% and 24.1%, respectively, compared to those in HFD control group. Enlarged adipocytes of HFD control group were markedly decreased in GINST-treated groups, and shrunken islets of HFD control mice were brought back to near normal shape in GINST300 group. Furthermore, GINST enhanced phosphorylation of AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4). In summary, GINST prevents HFD-induced hyperglycemia and hyperlipidemia through reducing insulin resistance via activating AMPK-GLUT4 pathways, and could be a potential therapeutic agent for type 2 diabetes.

• Journal of Acupuncture Research
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• 제27권6호
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• pp.31-42
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• 2010

Objectives : The aim of this study was to investigate the anti-obesity potential and mechanisms of action of Rhizoma Atractylodis(RA) herbal acupuncture in high fat diet- induced obese ICR mice. Methods : Sample solutions for herbal acupuncture were prepared from the Rhizoma Atractylodis water extract powder at concentration of 150mg/kg and 300mg/kg with distilled water. Five week-old ICR mice acclimatized to the laboratory environment for 1 week were allocated into four groups: regular diet group (RD), high fat diet group(HFD), groups fed HFD with 150mg/kg RA herbal acupuncture treatment (RAE 150) and with 300mg/kg RA herbal acupuncture treatment(RAE 300). Herbal acupuncture groups were injected with either 150mg/kg or 300mg/kg of Rhizoma Atractylodis(RA) subcutaneously onto both Sinsu($BL_{23}$) alternately on the same time everyday for 30days. Body weight, gross appearance of epididymal fat area, blood glucose, insulin, insulin resistance(HOMA-IR), non-esterified fatty acid, cholesterol, triglyceride, AST, ALT, histological analysis of white adipose tissue, gene expression responsible for adipocyte differentiation and AMPK activation were analyzed. Results : RA herbal acupuncture inhibited the development of weight gain, hyperglycemia, hyperinsulinemia, hyperlipidemia, increases of AST and ALT, and the enlargement of fat cell size induced by HFD. Also, RA herbal acupuncture inhibited the expression of PPAR-${\gamma}$, C/$EBP{\alpha}$, aP2, LPL, FAS, SCD-1 and enhanced the activation of AMP-activated protein kinase. Conclusions : The results of this study demonstrate that RA herbal acupuncture can exert the anti-obesity effect and it is partially mediated by activation of AMPK and inhibition of the gene expressions responsible for adipocyte differentiation. Further studies will be required to ascertain the nti-obesity effect and mechanisms of action of RA herbal acupuncture in animal models and human for aclinical application.

• 생약학회지
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• 제47권3호
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• pp.264-272
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• 2016

This study was carried out to evaluate the preventive effect of the Corni Fructus (SSU) 50 % EtOH extract (SSU-E50) against bisphenol A (BPA) toxicity in Leydig cells and improving testosterone deficiency syndrome in orchidectomized Sprague-Dawly (SD) rats. Antioxidant properties were measured by radical scavenging activity of SSU-E50 in ABTS assay and DPPH assay. Also, real-time polymerase chain reaction(real-time PCR) was performed to quantify the mRNA expression levels of antioxidant enzyme. SD rats were divided into eight group: normal, sham operation (Sham), orchidectomized (ORX), ORX treated with testosterone 1 mg/kg (Tes. 1), ORX treated with SSU water extract 100 mg/kg (SSU-A 100) and 300 mg/kg (SSU-A 300), ORX treated with SSU 50 % EtOH extract 100 mg/kg (SSU-E 100) and 300 mg/kg (SSU-E 300). On a comparative basis, the SSU showed better activity quenching ABTS with an IC50 value of 0.29 mg/ml and DPPH with an IC50 value of 0.33 mg/ml. Cell viability was evaluated by MTS assay as described not cytotoxic at the highest concentration of $500{\mu}g/ml$. Cytotoxicity of BPA showed in $200{\mu}M$, but definitely survived by treatment with SSU in Leydig cells. In addition, SSU increased the mRNA expression levels of antioxidant enzyme in BPA induced Leydig cells. Superoxide dismutase (SOD) level was slightly increased and malondialdehyde (MDA) level was decreased with SSU-A 100 in in-vivo. These results suggest that Corni Fructus extracts have the greatest property as a natural anti-oxidative and improves testosterone deficiency syndrome source.

• Toxicological Research
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• 제18권1호
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• pp.47-57
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• 2002

The subacute oral toxicity of 1-(4-methylpiperazinyl)-3-phenylisoquinoline (CWJ- a-5) was investigated in Sprague-Dawley (SD) rats. Five groups of 5 males and 5 females were orally administered at doses of 0, 37.5, 75, 150 and 200 mg/kg with CWJ-a-5 for 2 weeks. In clinical signs, Salivation was observed in the 75, 150 and 500 mg/kg male and female groups. Loss of fur was observed in the 500 mg/kg male and female group. Body weight were significantly decreased in the 150 and 500 mg/kg male groups and in the 500 mg/kg female group. Food consumption was significantly decreased in the 300 mg/kg male group. In serum biochemistry, total cholesterol and phospholipid were significantly increased in 500 mg/kg male and female group. Aspartate aminotransferase was significantly increased in the 500 mg/kg female group. In histopathological examination, vacuolar degeneration of renal tubules in the kidney, vacuolar degeneration of hepatocytes in the liver vacuolar degeneration of myocytes in the heart, vacuolar degeneration of histiocytes in the spleen and thymus, atrophy of seminiferous tubule and degeneration of germinal epithelium in the testis, vacuolar degeneration of corpus luteum, granulosa cell and theca cell in the ovary were observed in the 150 and 500 mg/kg male and female groups. Based on these results, the no observed adverse effect level (NOAEL) with CWJ-a-5 was considered to be 75 mg/kg and the absolute toxic dose was considered to be 150 mg/kg in this study

• 생명과학회지
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• 제20권4호
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• pp.496-502
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• 2010

산성 식염수 쥐모델은 사람의 섬유근통에 근접한 모델로 제시되고 있다. 포도씨에서 얻은 oligomeric proanthocyanidin complexes (OPC)는 항산화제로 알려져 있다. 저자들은 산성 식염수 모델에서 통증 역치에 대한 OPC의 효과를 연구했다. 좌측 장딴지 근육에 pH 4.0의 산성 식염수 $100\;{\mu}l$를 0일과 5일에 주사했다. 대조군은 pH 7.2의 생리 식염수를 같은 스케줄로 주사했다. 산성 식염수 그룹 10마리를 다시 두 그룹으로 나누어 한 그룹은 멸균 식염수, 다른 한 그룹은 OPC 300 mg/kg를 복강 내 주사했다. 복강 내 주사 한시간 후 다시 통각에 대한 역치를 조사했다. 0일에 비해 7일에서 산성 식염수 모델은 기계적 과통각을 나타냈다(p<0.05). OPC 300 mg/kg를 복강내 주사한 그룹에서 강력한 항통각 효과를 나타냈다(주사측 발바닥, p=0.001; 반대측 발바닥, p=0.002). 면역조직화학 염색상 복강내 식염수를 처치한 대조군에 비해 OPC 처치군에서 대뇌의 M1 및 M2 영역에서 산-감지 이온 통로3의 발현이 감소되었다(p<0.05). 사람의 섬유근통에서 OPC 치료의 효과를 보기 위한 연구가 향후 필요할 것으로 생각된다.

• 생명과학회지
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• 제14권1호
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• pp.141-147
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• 2004

가자 추출물을 흰쥐에 일정량 투여한 후 간장에 미치는 영향을 관찰할 목적으로 여러 가지 효소량의 변동을 검토하였다. 간 손상의 지표로 사용되는 AST, ALT활성을 측정한 결과 AST, ALT모두에서 정상군보다 300 mg/kg의 용량으로 2주 시료 투여한 군의 함량이 2배 이상 증가되는 것으로 나타났다. 가자 추출물이 지질과산화물 생성에 미치는 효과를 관찰한 결과, 300 mg/kg의 용량으로 2주 시료 투여한 군함량이 정상군에 비해 135.43%, 173.9% 정도 증가하는 결과를 나타내었다. 간 조직의 지질과산화물 반응에 관여하는 것으로 알려진 XO, AO, AD 및 AH활성에 대한 효과를 관찰한 결과 마이크로솜 분획에 존재하는 AD, AH의 활성은 저해 효과가 없었고, 세포질 효소인 XO, AO의 활성은 300 mg/kg의 용량으로 2주 시료 투여한 군 함량이 정상군에 비해 약 2배 증가됨을 볼 수 있었다. 가자 추출물에 의한 간 조직중 glutathione농도에 미치는 영향에 대해 관찰한 결과 2주 동안 300 mg/kg의 용량으로 투여한 군의 glutathione농도는 정상군에 비해 약 75% 감소하는 것으로 나타났다 가자 추출물 투여 후 glutathione의 함량 감소를 경감시키는 기전을 알아볼 목적으로 glutathione 합성에 관여하는 $\gamma$-GCS의 활성과 산화형 glutathione을 환원형 glutathione으로 환원시키는 GR의 활성을 관찰한 결과 정상군에 비해 GR이 56.6%, $\gamma$-GCS가 6.7% 정도 감소하는 것으로 나타났다. 이러한 glutathione의 함량 변동은 산화형 glutathione을 환원형 glutathione으로 환원시키는 GR의 활성에 영향을 주어 나타나는 결과로 생각된다. 가자 추출물이 지질과산화의 해독계에 미치는 영향을 관찰할 목적으로 catalase, GP 및 SOD의 활성을 측정한 결과 catalase, GP의 활성은 각각 77.5%, 64.3% 감소하는 결과를 나타냈으며, SOD의 활성은 정상군에 비해 약 3배 증가하는 것으로 나타났다.

• 대한본초학회지
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• 제33권4호
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• pp.9-18
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• 2018

Objectives : This study aimed to investigate the anti-ulcer effect of an standardized herbal extracts mixture of Inulae Flos and Paeoniae Radix (HT074) on acidified ethanol induced gastric injury and its potential mechanisms. Methods : Antioxidant activities of HT074 and its constituents were measured by DPPH (2,2-Diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging capacity. After the oral administration of HT074 at doses of 100, 300 mg/kg twice per day for 14 days, Gastric lesions were induced by oral administration of acidified ethanol in Sprague Dawley rats. Oxidative stress markers, such as super oxide dismutase (SOD) activity, concentrations of catalase (CAT) and glutathione (GSH) were measured in gastric mucosal tissues. Additionally, the expression of human mucin gene, Mucin 5AC (MUC5AC) mRNA in gastric mucosal tissues was measured. Results : HT074 showed dose dependent radical scavenging activities against DPPH and ABTS radicals. Oral administration of HT074 300 mg/kg for 14 consecutive days significantly decreased gastric lesions and histological damages induced by HCl/EtOH in rats. HT074 treatment significantly increased the activity of SOD (300 mg/kg) and concentration of GSH (100 and 300 mg/kg), however catalase concentration was not significantly increased. MUC5AC mRNA expression was significantly increased by HT074 100, 300 mg/kg treatment. Conclusions : HT074 protects the gastric mucosa from oxidative stress caused by acidified ethanol by increasing the activity of SOD, concentration of GSH and mucin biosynthesis. These findings suggest that HT074 could be an effective candidate for prevention and treatment of gastritis and gastric ulcer.

• 생명과학회지
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• 제17권4호
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• pp.561-567
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• 2007

본 연구는 김치로부터 분리한 EPS생성 유산균 Leu. kimchii GJ2에 대한 급성독성시험을 위하여 복강 및 경구로 1회 시료물질을 최고 용량(복강: 2,500 mg/kg, 경구: 5,000 mg/kg)으로, 10마리 ICR계통 암수 마우스에게 투여한 후 14일간의 일반증상, 사망률, 체중, 임상증상 및 육안적 소견을 관찰하였다. 복강 및 경구투여한 후 24시간 이내에 일부 시료투여군에서 부분적으로 사망례가 관찰되었으나 나머지 시험동물은 계속 생존하여 평균치사량을 산출할 수 없었다. 복강 혹은 경구투여한 후 마우스의 체중변화에 있어서도 암수 모두 대조군과 시료물질 투여군 사이에 유의성 있는 차이는 보이지 않았으며, 생존동물의 부검결과에서도 내부장기의 육안적 이상 소견도 관찰되지 않았다. 이상의 결과로부터 시험물질인 Leu. kimchii GJ2는 복강 및 경구투여 시 마우스에서 독성학적인 변화가 관찰되지 않았으며, $LD_{50}$은 복강투여가 2,500 mg/kg, 경구투여가 5,000 mg/kg 이상인 저독성의 안전한 물질로 사료된다.