개에서 진드기 살충제 amitraz의 단회피하투여 독성시험

허정두,김영길,이현숙,김충용,박승춘,신진영,김성호,신동호,김종춘 한국생명과학회 2004 생명과학회지 Vol.14 No.4

본 연구는 살충제 amitraz의 피하투여 급성독성을 평가하기 위해 0, 2, 10 및 50 mg/kg용량으로 1회 피하투여한 후, 사망률과 일반증상, 체중, 혈액 및 혈청생화학 및 부검소견에 미치는 영향을 평가하였다. 시험결과, 비글 개에 있어서 amitraz의 단회 피하투여는 식욕부진과 침울, 구토, 유루, 운동성감소, 보행실조, 투여부위의 부종, 종괴 및 농양형성, 사지의 부전마비, 횡와위, 빈사, 사망, 체중감소, 투여부위의 근육출혈과 염증, 그리고 간과 신장의 충혈을 유발하는 것으로 나타났다. 반면, 투여 후 14일째에 생존동물의 혈액 및 혈청생화학치에서는 시험물질의 투여와 관련된 어떠한 변화도 인정되지 않았다. 결론적으로 본 시험조건하에서 비글 개에 대한 amitraz의 반수치사량은 22.3 mg/kg (95% 신뢰 한계: 산출되지 않음)이고, 무해용량(no-observed-adverse-effect level)은 2 mg/kg 이하로 사료된다. The present study was carried out to investigate the potential acute toxicity of amitraz by a single subcutaneous dose in beagle dogs. The test chemical was administered subcutaneously to male beagle dogs at dose levels of 0, 2, 10, or 50 mg/kg. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period following the administration. At the end of 14-day observation period, hematology, serum biochemistry, and gross postmortem examinations were examined. A single dog in the 50 mg/kg group was found dead on day 3 after treatment and the other two dogs in the group were sacrificed because of the severe clinical signs on day 7 after treatment. Treatment related clinical signs, including anorexia, edema, mass and abscess formation in the injection sites, depression, vomiting, lacrimation, decreased locomotor activity, ataxia, recumbency, paresis in the limbs, and/or moribundity were observed in all treatment groups in a dose-dependent manner. Decreased or suppressed body weight gain was also observed dose-dependently in all treated groups. In autopsy, dead animals in the 50 mg/kg group showed muscular hemorrhage and inflammation in the injection sites and congestion in the liver and kidney. The terminal sacrificed animals in the 10 mg/kg group also exhibited muscular hemorrhage and inflammation in the injection sites. Whereas, no treatment related effects on hematology and serum biochemistry were observed on day 14 after treatment at any dose tested. On the basis of the results, it was concluded that a single subcutaneous injection of amitraz to beagle dogs resulted in increased incidence of abnormal clinical signs and death, decreased body weight, and increased incidence of abnormal gross findings. In the experimental conditions, the $LD_{50}$value of amitraz was 22.3 mg/kg (95% confidence limit not specified) and the no-observed-adverse-effect level (NOAEL) was considered to be below 2 mg/kg for male dogs.

임신 중 환경오염물질 2-Bromopropane에 노출된 마우스의 모독성 평가

허정두(Jeong-Doo Heo),김충용(Chung-Yong Kim),강성철(Chen-Zhe Ziang),서정은(Jeong-Eun Suh),정문구(Moon-Koo Chung),김무강(Moo-Kang Kim),신동호(Dong-Ho Shin),김종춘(Jong-Choon Kim) 한국실험동물학회 2004 Laboratory Animal Research Vol.20 No.1

2-Bromopropane (2-BP), a halogenated propane analogue, is a substitute for chlorofluorocarbones (CFCs). The present study was carried out to investigate the potential adverse effects of 2-BP on pregnant dams after maternal exposure during the gestational days (GD) 6 through 17 in ICR mice. The test chemical was administered subcutaneously to pregnant mice at dose levels of 0, 500, 1000, and 1500 ㎎/㎏/day. All pregnant females were subjected to autopsy on GD 18. Treatment-related clinical signs, as evidenced by dose-dependent increases in the incidence and severity of rough fur, swelling, induration, crust formation, and ulceration at the injection sites, were observed at dose levels of above 1000 ㎎/㎏/day. Maternal body weight on GD 18 and maternal body weight gain for the intervals GD 6-17 (treatment period) were suppressed at a dose level of 1500 ㎎/㎏ in a dose-dependent manner, but not statistically significant. Hematological investigations revealed a dose-dependent decrease in the number of platelet at a dose level of 1500 ㎎/㎏. Fetal body weights of both sexes in the 1500 ㎎/㎏ group were also decreased in a dose-dependent manner. There were no adverse effects on mortality, food consumption, organ weights, and reproductive findings except for decreased fetal body weight in any treatment group. Based on these results, it was concluded that the 12-day repeated subcutaneous dose of 2-BP resulted in an increased incidence of clinical signs, suppressed maternal body weight, reduced platelet count and decreased fetal body weight at a dose level of 1500 ㎎/㎏/day in pregnant mice. In the present experimental conditions, the no-observed-adverse-effect level of 2-BP was considered to be 500 ㎎/㎏ for dams.

The Influence of Restraint Inhalation Chamber (nose-only) on Physiological Parameter in Mice

김수남,허정두,강민성,한영아,김재환,이진수,이규홍,송창우 한국실험동물학회 2009 한국실험동물학회 학술발표대회 논문집 Vol.2009 No.2

LPS로 유도된 RAW264.7 대식세포에 대한헛개나무(Hovenia dulcis) 추출물의 항염증 효과

우현심,이선민,허정두,이민성,김영수,김대욱 한국자원식물학회 2018 한국자원식물학회지 Vol.31 No.5

In this study, the anti-inflammatory activities of the extracts of different parts of Hovenia dulcis such as leaves, stems, and roots were investigated. Among them, the roots extract (RE) showed the most potent suppressive effect against pro-inflammatory mediators in LPS-stimulated mouse macrophage cells. RE induced dose-dependent reduction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and concomitantly reduced the production of NO and PGE2. Additionally, pre-treatment with RE significantly suppressed the production of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, as well as mRNA levels. Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-kB) were also strongly attenuated by RE in RAW264.7 cell. Furthermore, RE induced HO-1 expression through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and increase HO-1 activity in RAW264.7 macrophages. Therefore, these results indicate that RE strongly inhibits LPS-induced inflammatory responses by blocking NF-kB activation, inhibiting MAPKs phosphorylation, and enhancing HO-1 expression in macrophages, suggesting that RE of H. dulicis and a major component, 27-O-protocatechuoylbetulinic acid could be applied as a valuable natural anti-inflammatory material. 본 연구는 헛개나무 잎, 줄기, 뿌리로부터 얻어진 메탄올 추출물의 항염증 효과를 구명하기 위해서 수행되었다. LPS로 염증이 유도된 RAW264.7 세포 내 부위별 추출물을 동시에 처리하여 염증 매개성 물질인 NO 생성량 분석 결과 40 ㎍/㎖ 농도에서뿌리(94.7%)와 줄기(42.6%)에서는 효과가 있는 반면 잎에서는효과가 없는 것으로 확인되었다. 이 중 탁월한 효과를 보인 뿌리추출물(RE)의 항염증 효과 및 관련 분자적 기전을 확인하였다. 그 결과, 염증 반응의 주요 경로인 NF-kB 및 MAPK 신호전달경로에서 RE가 LPS로 유도된 NF-kB의 핵 이동을 억제하고, ERK, JNK, p38의 인산화를 억제함으로써 iNOS, COX-2의 발현이 감소되고, NO와 pro-inflammatory cytokine (IL-6, IL-1β, TNF-α)의 생성이 억제됨을 확인하였다. 또한 RE는 대식세포에서 Nrf2를 활성화시켜 항염증성 단백질인 HO-1 발현을 유도하여 항염증 효과를 나타내었다. 또한, RE로부터 주요 성분을 분리한 후 NMR과 MS 기기를 이용하여 구조 동정된 27-Oprotocatechuoylbetulinic acid 화합물에서도 높은 항염증 효과를 확인하였다. 이러한 연구결과는 헛개나무뿌리와 그 주요성분은 의약품 소재 및 기능성 식품 등의 기능성 소재로 활용될수 있는 기초적인 정보를 제공할 것으로 생각된다.

Dihydrobenzofuran Neolignans Isolated from Euonymus alatus Leaves and Twigs Attenuated Inflammatory Responses in the Activated RAW264.7 Macrophage Cells

김나현,양민혜,허정두,성상현,정은주 한국생약학회 2016 Natural Product Sciences Vol.22 No.1

Anti-inflammatory effects of dihydrobenzofuran neolignans isolated from Euonymus alatus leaves and twigs were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Six neolignans, (+)-simulanol (1), (+)-dehydrodiconiferyl alcohol (2), (-)-simulanol (3), (-)-dehydrodiconiferyl alcohol (4), (+)-dihydrodehyrodiconiferyl alcohol (5), threo-buddlenol B (6) effectively inhibited the production of nitric oxide (NO) induced by LPS, and the activity of iNOS. (-)-dehydrodiconiferyl alcohol (4), which showed the most potent inhibitory activity, attenuated the activity of iNOS enzyme and also the expression of iNOS and COX-2 proteins. The subsequent production of pro-inflammatory cytokines, interleukin-1b, interleukin-6, tumor necrosis factor-a and prostaglandin E2 were also inhibited by the pretreatment of RAW264.7 cells with (-)-dehydrodiconiferyl alcohol (4). These neolignans are thought to contribute to anti-inflammatory effects of E. alatus, and expected to be potential candidates to prevent/treat inflammation-related diseases.

Toxicological comparison of BPA, BPS, BPF and TMBPF in Caenorhabditis elegans

황광현,현문정,허정두 환경독성보건학회 2021 한국독성학회 심포지움 및 학술발표회 Vol.2021 No.10

랫드에서 fluoroquinolone 항균제 DW-116 의 단회 경구투여에 의한 태반통과와 약물동태연구

김종춘,윤효인,신호철,허정두,이종화,정문구 한국응용약물학회 2002 Biomolecules & Therapeutics(구 응용약물학회지) Vol.10 No.4

Melatonin protects against cadmium-induced oxidative stress via mitochondrial STAT3 signaling in human prostate stromal cells

현문정,김혜진,한성민,허정두 환경독성보건학회 2023 한국독성학회 심포지움 및 학술발표회 Vol.2023 No.5

The Extract of Limonium tetragonum Protected Liver against Acute Alcohol Toxicity by Enhancing Ethanol Metabolism and Antioxidant Enzyme Activities

Na-Hyun Kim,성상현,허정두,정은주 한국생약학회 2015 Natural Product Sciences Vol.21 No.1

The protective effect of EtOAc fraction of Limonium tetragonum extract (EALT) against alcohol-induced hepatotoxicity was assessed following acute ethanol intoxication in Spraque-Dawley rats. EALT (200 mg/kg p.o.) was administrated once before alcohol intake (8 g/kg, p.o.). Blood ethanol concentration, and the activities of alcohol metabolic enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the liver were measured. Also, the formation of malondialdehyde (MDA) and the activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase were determined after acute alcohol exposure. Pretreatment of rats received ethanol with EALT significantly decreased blood ethanol concentration and elevated the activities of ADH and ALDH in liver. The increased MDA level was decreased, and the reduced activities of SOD, GSH-px and catalase were markedly preserved by the treatment with EALT. This study suggests that EALT prevent hepatic injury induced by acute alcohol which is likely related to its modulation on the alcohol metabolism and antioxidant enzymes activities.

Antiobesity Effect of Fermented Chokeberry Extract in High-Fat Diet-Induced Obese Mice

김나현,제갈종환,김윤나,정동민,허정두,노정래,양민혜,정은주 한국식품영양과학회 2018 Journal of medicinal food Vol.21 No.11

Black-fruited chokeberries (Aronia melanocarpa), growing mainly in the Central and Eastern European countries, have health benefits due to the high concentrations of polyphenolic compounds. However, a strong bitter taste of chokeberries limits its usage as functional food. We hypothesized that the fermented A. melanocarpa with a reduced bitter taste would improve insulin sensitivity and/or ameliorate weight gain induced by high-fat diet (HFD) in male C57BL/6J mice. The mice were administered with HFD together with the 100 mg/kg of natural A. melanocarpa (T1) or the fermented A. melanocarpa (T2) for 8 weeks. The treatment with T2 (100 mg/kg body weight, p.o.) markedly attenuated the weight gain and the increase in serum triglyceride level induced by HFD. The T2-treated group had better glucose tolerance and higher insulin sensitivity as measured by oral glucose tolerance test and intraperitoneal insulin tolerance test in comparison to the T1-treated group. Phytochemical analysis revealed that the main constituents of T2 were cyanidin-3-xyloside and 1-(3',4'- dihydroxycinnamoyl)cyclopenta-2,3-diol, and the content of cyanidin glycosides (3-glucoside, 3-xyloside) was significantly reduced during the fermentation process. From the above results, we postulated that antiobesity effect of black chokeberry was not closely correlated with the cyanidin content. Fermented chokeberry might be a viable dietary supplement rich in bioactive compounds useful in preventing obesity.