• 생명과학회지
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• 제30권4호
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• pp.321-330
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• 2020

본 연구의 목표는 CuCl₂가 지브라피시에 미치는 영향을 조사하는 것이다. CuCl₂에 대한 지브라피시의 반수치사농도를 조사하기 위하여 각기 다른 시간에 따른 농도를 설정하여 노출시켰다. 본 연구에서는 스트레스 반응의 증가를 보기 위하여 whole-body cortisol level 측정과 행동약리학적 변화를 측정하기 위해서 open field test와 novel tank test를 실시하였다. Whole-body cortisol의 sample을 수집하거나 행동실험을 실시하기 전에 CuCl₂ 또는 vehicle을 1시간 동안 처리하였다. CuCl₂의 반수치사농도는 24시간, 48시간, 96시간에서 각각 30.3, 25.3, 14.8 ㎍/l으로 측정되었다. CuCl₂에 노출된 지브라피시의 novel tank test의 결과는 총 이동거리, 움직이는 시간 그리고 속도는 유의성이 있게 감소한 반면, turn angle은 최고농도에서 유의성이 있게 증가하였다(p<0.05). 다른 행동실험인 open field test의 결과에서도 총 이동거리, 움직이는 시간 속도가 CuCl₂의 노출에 의해서 감소하였으며, turn angle과 meandering이 유의하게 증가하였다(p<0.05). CuCl₂에 노출된 지브라피시의 whole-body cortisol은 1.5 or 15 ㎍/l의 농도에서는 유의하게 증가하였으나, 150 ㎍/l의 농도에서는 유의성 있는 변화를 발견하지 못하였다(p<0.05). 본 연구의 결과는 CuCl₂의 노출이 지브라피시에서 치사율 증가, 행동 및 내분비의 변화 등을 포함하는 독성 반응을 야기하는 것을 나타낸다.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 춘계학술대회
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• pp.156-157
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• 2003

The goal of this study is to develop a biomarker used in monitoring abnormal behaviors of Japanese medaka (Oryzias latipes) as a model organism caused by hazardous chemicals. Japanese medaka was treated under appropriate sublethal concentrations of copper and the fish were subjected to copper treatment after starvation for 48 hr. The untreated individuals showed common behavioral characteristics (i.e., smooth and linear movements with small curvatures) in the movement behaviors.

• 약학회지
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• 제39권1호
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• pp.55-60
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• 1995

The acetone precipitates of the hot water extract of Torilis ftuctus showed strong hemostatic activity which was not inhibited by aspirin. This activity was not through platelet activation but possibly through activating some coagulation factors in plasma. The hemostatic action of the precipitates was not active by oral adminitration and no behavioral toxicity was appeared in treated mice. However, mice treated with the acetone precipitates through tail vein showed serious tremor and then were killed probably by the thrombus produced in the body. The hemostatic activity was still remained after treatment with $\beta$-glucosidase, $\beta$-alactosidase, $\alpha$-amylase, subtilisin BPN', or trypsin but completely lost by acid hydrolysis. The active components seemed to be a complex of unidentified macromolecules to which some phenolic compounds were strongly bound.

• 한국어업기술학회:학술대회논문집
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• 한국어업기술학회 2001년도 춘계 수산관련학회 공동학술대회발표요지집
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• pp.265-266
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• 2001

PCDDS and PCDFs are very stable chcmicals and have very long residence times in the environment and in organisms, including humans. Their hydrophobicity promotes accumulation in sediments and organisms, resulting in high concentrations in both sediments and organisms. Among toxicological effects reports arc teratogenicity, reduce reproduction, liver toxicity, decreased growth rate and behavioral changes (Zeise et al., 1990; Huff, 1992). PCDDs/DFs are inadvertently produced from various combustion sources and manufacturing processes, such as municipal solid waste incineration (Olie et at., 1977), motor vehicles (Marklund et al., 1987), steel mills (Tysklind et al., 1989), and chemical production processes (Hutzinger et al., 1985). (omitted)

• 생명과학회지
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• 제26권2호
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• pp.181-189
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• 2016

본 연구에서는 발아전처리 제초제인 Dithiopyr (DTP)를 시험물질로 사용하여 급성 독성시험을 평가하고, zebrafish의 행동에 미치는 영향을 연구하였다. 급성 독성시험 결과 zebrafish에서의 DTP의 LC₅₀값은 14.49 μM이었다. 또한 DTP 노출이 유영 패턴에 미치는 영향을 관찰하기 위하여 아치사농도(2.5-20 μM)에서 novel tank test (NTT)와 open field test (OFT)의 두 가지 행동실험을 실시하였다. NTT를 실시한 결과, 하층부의 머무는 시간 및 최초로 상층부에 들어간 시간, 회전각, 부동 시간의 경우 control 그룹과 비교하여 통계적으로 유의성 있게 농도 의존적으로 증가하였다(p<0.05). 또한 상층부에 진입한 횟수 및 평균 유영속도에서 통계적인 유의성 있는 감소현상이 확인되었다(p<0.05). OFT를 실시한 결과, 총 이동 거리 및 평균 유영속도에서 유의성이 있는 감소현상이 확인되었다(p<0.05). 부동 시간 및 회전각, 굴곡유영에서는 유의성 있는 증가 현상이 확인되었다(p<0.05). 또한 Whole-body cortisol level 측정 결과, 저농도 노출 그룹에서만 유의성 있는 증가가 관찰되었으나(p<0.05), 5와 10 μM에서는 유의성 있는 차이가 관찰되지 않아 농도의존적으로 감소하는 것을 확인하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제17권1호
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• pp.89-97
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• 2013

Developing an animal model for a specific disease is very important in the understanding of the underlying mechanism of the disease and allows testing of newly developed new drugs before human application. However, which of the plethora of experimental animal species to use in model development can be perplexing. Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a very well known method to induce the symptoms of Parkinson's disease in mice. But, there is very limited information about the different sensitivities to MPTP among mouse strains. Here, we tested three different mouse strains (C57BL/6, Balb-C, and ICR) as a Parkinsonian model by repeated MPTP injections. In addition to behavioral analysis, endogenous levels of dopamine and tetrahydrobiopterin in mice brain regions, such as striatum, substantia nigra, and hippocampus were directly quantified by liquid chromatography-tandem mass spectrometry. Repeated administrations of MPTP significantly affected the moving distances and rearing frequencies in all three mouse strains. The endogenous dopamine concentrations and expression levels of tyrosine hydroxylase were significantly decreased after the repeated injections, but tetrahydrobiopterin did not change in analyzed brain regions. However, susceptibilities of the mice to MPTP were differed based on the degree of behavioral change, dopamine concentration in brain regions, and expression levels of tyrosine hydroxylase, with C57BL/6 and Balb-C mice being more sensitive to the dopaminergic neuronal toxicity of MPTP than ICR mice.

• Biomolecules & Therapeutics
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• 제27권2호
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• pp.168-177
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• 2019

Dysregulation of excitatory neurotransmission has been implicated in the pathogenesis of neuropsychiatric disorders. Pharmacological inhibition of N-methyl-D-aspartate (NMDA) receptors is widely used to model neurobehavioral pathologies and underlying mechanisms. There is ample evidence that overstimulation of NMDA-dependent neurotransmission may induce neurobehavioral abnormalities, such as repetitive behaviors and hypersensitization to nociception and cognitive disruption, pharmacological modeling using NMDA has been limited due to the induction of neurotoxicity and blood brain barrier breakdown, especially in young animals. In this study, we examined the effects of intraperitoneal NMDA-administration on nociceptive and repetitive behaviors in ICR mice. Intraperitoneal injection of NMDA induced repetitive grooming and tail biting/licking behaviors in a dose- and age-dependent manner. Nociceptive and repetitive behaviors were more prominent in juvenile mice than adult mice. We did not observe extensive blood brain barrier breakdown or neuronal cell death after peritoneal injection of NMDA, indicating limited neurotoxic effects despite a significant increase in NMDA concentration in the cerebrospinal fluid. These findings suggest that the observed behavioral changes were not mediated by general NMDA toxicity. In the hot plate test, we found that the latency of paw licking and jumping decreased in the NMDA-exposed mice especially in the 75 mg/kg group, suggesting increased nociceptive sensitivity in NMDA-treated animals. Repetitive behaviors and increased pain sensitivity are often comorbid in psychiatric disorders (e.g., autism spectrum disorder). Therefore, the behavioral characteristics of intraperitoneal NMDA-administered mice described herein may be valuable for studying the mechanisms underlying relevant disorders and screening candidate therapeutic molecules.

• Environmental Analysis Health and Toxicology
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• 제18권2호
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• pp.145-153
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• 2003

The goal of this study is to develop a biomarker used in monitoring abnormal behaviors of Japanese medaka (Oryzias latipes) as a model organism caused by hazardous chemicals. Japanese medaka was treated by copper of appropriate sublethal concentrations after starvation for 48 hr. The untreated individuals showed common behavioral characteristics (i.e. , smooth and linear movements). Locomotive activity of the fish was monitored using an image processing and automatic data acquisition system. When treated with copper (100 ppb), the fish showed shaking patterns more frequently. As the concentration of copper increased to 1,000 ppb, activity decreated, and the fish showed an erratic movement. Fish were exposed to copper at various concentrations (0,100 and 1,000 ppb) for 24 hrs, and acetylcholine esterase (AChE) activity was observed. When fish were exposed to 1,000 ppb of copper, the body AChE activities appeared to decrease but the head AChE activities showed little change. Expressions of tyrosine hydroxylase (TH) protein in the different organs from both head (brain) and body (kidney) portions affected by the copper treatment were analyzed using immunohistochemical technique compared with control. Five organs of the fish (olfactory bulb, hyothalamus, optic lobe, pons and myelencephalon regions) showed a relatively strong TH protein expression in the control experiment. A differential expression of TH, however, was observed in the treatment (100 ppb and 1,000 ppb). The treatment (1,000 ppb) significantly suppressed TH protein production in the brain regions. In kidney, however, the same treatment caused little suppression compared with the control. Copper appeared to be less effective in suppression of TH than diazinon, a known TH suppressor. It was concluded that TH could be used at a potential biomarker to monitor the acute copper toxicity in Japanese medaka.

• Toxicological Research
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• 제17권
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• pp.135-138
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• 2001

Female Wistar rats were randomly divided into 5 groups: Control, received distilled water; Low lead, received 0.5 g/ιlead (as acetate) in drinking water; High lead, received 2.0 g/ιlead; Low lead + Minerals, received 0.5 g/ιlead in drinking water and received minerals (Ca$^{2+}$, 25 mg/kg/day; Fe$^{3+}$, 0.47 mg/ kg/day; Zn$^{2+}$, 0.33 mg/kg/day; Se, 0.83 $\mu\textrm{g}$/kg/day) by gavage; High lead + Minerals, received 2.0 g/ιlead and received the same minerals. Animals exposure to lead was from 10 days before mating till postnatal day 21; and the minerals was administered from the first day of pregnancy and during lactation. No statistical difference was found either in body weights or in blood lead levels between the pups received minerals and those only exposed to lead at the same dose. The developmental and behavioral teratological effects of lead on pups, such as time-lag of eye opening, pinna detachment, fur developing, incisor eruption, ear unfolding, and surface righting were observed in this study; and the minerals decreased the toxicity of lead either in low or in high lead exposure pups. The numbers of step-down were significantly increased in lead exposed animals, and the effect of intervention by the minerals was appeared only in the pups exposed to low lead. The ChAT activity and levels of glutamate and aspartate in hippocampus decreased in treated animals compared to control animals, no effect of intervention by the minerals was found. The results of this study indicate that the applied multi-minerals can alter the outcome of develop-mental lead poisoning in rats.s.s.s.

• 대한수의학회지
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• 제51권3호
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• pp.185-191
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• 2011

Trimethyltin chloride (TMT) has been used as a neurotoxin for inducing brain dysfunction and neuronal death. Neuronal death in the hippocampus by TMT may generate excessive nitric oxide, but there are few studies about nitric oxide synthase enzyme involved in the synthesis of nitric oxide. The purpose of present study is to analyze the TMT toxicity in each region of rat hippocampus. To evaluate the involvement of nitric oxide, we analyzed the effects of aminoguanidine known as a selective inhibitor for inducible nitric oxide synthase on behavioral changes and the hippocampus of rat by TMT toxicity. 6-week-old male Sprague-Dawley rats were administered with a single dose of TMT (8 mg/kg b.w., i.p.) and the control group was similarly administered with distilled water. TMT + aminoguanidine-treated groups were administered with aminoguanidine (10 mg/kg or 100 mg/kg b.w., i.p.) for 3 days prior to TMT injection. The rats were sacrificed 2 days after TMT administration. In the TMT-treated group, a number of cell losses were seen in CA1, CA3 and the dentate gyrus. In the TMT + aminoguanidine-treated group, neuronal death was seen in CA1 and CA3, but reduced in the dentate gyrus compared to the TMT-treated group. Western blot analysis showed that cleaved caspase-3 expression was increased in the TMT-treated group compared to the control group. However, the expression significantly declined in the TMT + aminoguanidine-treated group. The present findings suggest that inducible nitric oxide synthase is involved in neuronal death induced by TMT.