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저널/프로시딩 상세정보

권호별목차 / 소장처보기

H : 소장처정보

T : 목차정보

한국독성학회지 = The Korean journal of toxicology 24건

  1. [국내논문]   $LD_{50}$의 독성학적 고찰  

    박현선 (성균관대학교 약학대학 ) , 홍채영 (성균관대학교 약학대학 ) , 오진아 (성균관대학교 약학대학 ) , 윤승천 (성균관대학교 약학대학 ) , 이병무 (성균관대학교 약학대학)
    한국독성학회지 = The Korean journal of toxicology v.12 no.2 ,pp. 143 - 154 , 1996 , 0258-2368 ,

    초록

    This paper reviews the toxicological role of median lethal dose ($LD_50$) based on animal and human data. Animal oral $LD_50$ values of eighty seven chemicals were collected and comparatively evaluated with human minimum toxic dose ($TD_50$). In general, animal $LD_50$ values were much higher than human $TD_50$. The ratios between $LD_50$ and TDlo were ranged from 0.01 and over 1000, suggesting safety factor of up to 1000 between humans and animals in the case of acute toxicity data. However, about 40% of chemicals investigated were within the ratio of 10. Although the cases (N=20) were small, $LD_50$ values of guinea pig were closer to human TDlo than those of other animal species. In interanimal species (rat, mouse, rabbit, dog), the ratios of $LD_50$ values were between 0.1 and 5 (up to 50-fold difference). When the data are analyzed by chemical strut-ares, human $TD_50$ values were very close to rat oral $LD_50$ values. These data suggest that rat oral $LD_50$ value might be a useful parameter predicting human TDlo and one animal species could be sufficient for acute toxicity test.

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  2. [국내논문]   대장균에서 발현된 인간 Cytochrome P450 1A1과 Rat NADPH-P450 Reductase와의 Fusion Protein의 효소 특성 연구  

    천영진 (한국화학연구소 안전성센터 ) , 정태천 (한국화학연구소 안전성센터 ) , 이현걸 (한국화학연구소 안전성센터 ) , 한상섭 (한국화학연구소 안전성센터 ) , 노정구 (한국화학연구소 안전성센터)
    한국독성학회지 = The Korean journal of toxicology v.12 no.2 ,pp. 155 - 161 , 1996 , 0258-2368 ,

    초록

    The enzymatic properties for NADPH-P450 reductase domain of a fusion protein between human cytochrome P450 1A1 and rat NADPH-P450 reductase expressed in Escherichia coli were investigated. The fusion plasmid pCW/1A1OR-expressed E. coli membrane showed high NADPH-cytochrome c reductase activity ($830.1\pm 85.8 nmol\cdot min^{-1}\cdot mg protein^{-1}$), while pCW control vector and P 450 1A1 expression vector pCW/1A1 showed relatively quite low activity ($4.35\pm 0.49, 3.27\pm 0.50 nmol\cdot min^{-1}\cdot mg protein^{-1}$, respectively). The kinetic curves for NADPH-cytochrome c reductase followed typical Michaelis-Menten kinetics. The $K_{max}$ and $V_{max}$ for NADPH-dependent reductase activity were $8.24\pm 2.61\mu $and $817.9\pm 60.8 nmol\cdot min^{-1}\cdot mg protein^{-1}$, respectively, whereas those for cytochrome c-dependent reductase activity were $19.97\pm 2.86\mu M$ and $1303.5\pm 67.1 nmol\cdot min^{-1}\cdot mg protein^{-1}$. The reductase activities were also compared with those of rat, porcine and human liver microsomes. The activity of pCW/ 1A1OR-expressed E. coli membrane was 15.2-fold higher than that of rat liver microsome. Treatment with benzo(a)pyrene, 7-ethoxyresorufin and $\alpha$-naphthofiavone which are known as specific substrates or inhibitor for human P450 1A1 increased NADPH-cytochrome c reductase activity of fusion protein in E. coli membrane dose-dependently. These results demonstrate that the membrane topology of fused enzyme may be important for activity of its NADPH-P450 reductase domain.

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  3. [국내논문]   Solid-Phase Extraction of Sulfamerazine from Shrimp Residue and Determination by Reversed Phase High Performance Liquid Chromatography  

    Jang, Won-Cheoul (Department of Chemistry, College of Natural Science, Dankook University ) , Heo, Gang-Joon (Laboratory of Aquatic Animal Disease, College of Veterinary Medicine, Chungbuk National University)
    한국독성학회지 = The Korean journal of toxicology v.12 no.2 ,pp. 163 - 169 , 1996 , 0258-2368 ,

    초록

    The focus of this study was to investigate the suitable analytical methods for measurement of sulfamerazine and its metabolite in shrimp hepatopancreas and tail tissue, in addition to the methods for the optimization of solid-phase extraction cartridge conditions and the elucidation of sulfamerazine concentrations in aqueous buffer using HPLC with UV and EC detectors. Compared with UV detector the EC detector appears to be 10 times more sensitive than that of the UV detector. After the shrimp was exposed to 10 ppm sulfamerazine, the accumulation levels of sulfamerazine and its metabolite in tail tissue, which is edible portion, were considerably lower than 0.1 ppm. The data indicate that sulfamerazine continues to be a candidate for use at levels of sulfamerazine concentration used in aquaculture of shrimp.

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  4. [국내논문]   Behavioral Effects of Mianserin on the Developmental Toxicity of Cocaine  

    Kang, Dong-Won (Department of Pharmacology, Yonsei University College of Medicine, Seoul, 120-752 ) , Kim, Dong-Goo (Department of Pharmacology, Yonsei University College of Medicine, Seoul, 120-752)
    한국독성학회지 = The Korean journal of toxicology v.12 no.2 ,pp. 171 - 179 , 1996 , 0258-2368 ,

    초록

    To investigate the involvement of $5-HT_{2A}/ 5-HT_{2C} receptors in the developmental toxicity of cocaine in rats, mianserin (2.5 mg/kg), a $5-HT_{2A}/5-HT_{2C}$ receptor antagonist, and/or cocaine HCl (45 mg/kg) were administered intraperitoneally (i.p.), during postnatal days (PND) 7-13. Behavioral assessments for the rat pups were done after 100 days of age by using the progressive ratio schedule of reinforcement (FR 1-FR 128, doubled everyday) and cocaine challenge (5, 15 or 30 mg/kg i.p.) upon established FR 32 behavior. Cocaine injected just prior to the FR 32 session suppressed the established FR 32 responding in a dose-dependent manner. The low dose of cocaine did not affect the FR 32 responding, while the high dose of cocaine suppressed it in all experimental groups. However, by the middle dose of cocaine, rats previously received water-cocaine in their early life showed a marked resistance to cocaine-induced behavioral suppression, and this resistance was not observed in rats received both mianserin and cocaine in their early life. These results suggest that $5-HT_{2A}/ 5-HT_{2C}$ receptors may have an important role for the persistently altered behavioral sensitivity to cocaine caused by exposure to cocaine during development.

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  5. [국내논문]   Sanjoinine-A의 중추신경계작용 및 일반약리작용  

    박찬웅 (서울대학교 의과대학 약리학교실 ) , 김용식 (서울대학교 의과대학 약리학교실 ) , 한병훈 (서울대학교 천연물과학연구소 ) , 박종완 (서울대학교 의과대학 약리학교실 ) , 장인진 (서울대학교 의과대학 약리학교실 ) , 최정윤 (서울대학교 의과대학 약리학교실 ) , 정동복 (서울대학교 의과대학 약리학교실 ) , 이윤송 (서울대학교 의과대학 약리학교실 ) , 김명석 (서울대학교 의과대학 약리학교실)
    한국독성학회지 = The Korean journal of toxicology v.12 no.2 ,pp. 181 - 194 , 1996 , 0258-2368 ,

    초록

    The effects of Sanjoinine-A, an alkaloid isolated from Zizyphus spinosus semens, on central nervous system and general pharmacology were studied. In summary, Sanjoinine-A depress the spontaneous locomotor activity without motor incoordination and it has slight analgesic effect. Those effects are qualitatively similar to that of diazepam but its potency is much lower than diazepam(20 times). Sanjoinine-A does not depress the electric or pentylenetetrazole induced convulsion. Those effects are dissimilar with that of diazepam. Sanjoinine-A slightly depress the spontaneous or acethylchollne induced motility of smooth muscles but degree of depressant effect was variable to tissues. Sanjoinine-A does not show any effects on digestive system, blood, kidney fuction and neural ganglion.

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  6. [국내논문]   Endotoxin에 의해 생성된 혈관의 nitric oxide가 교감신경계에 미치는 영향  

    박관하 (군산대학교 해양산업대학 수족병리학과)
    한국독성학회지 = The Korean journal of toxicology v.12 no.2 ,pp. 195 - 201 , 1996 , 0258-2368 ,

    초록

    Endotoxic shock causes death in humans and animals via extreme hypoperfusion of peripheral organs. A massive production of nitric oxide (NO) both from the endothelical cells and smooth muscle cells has been proposed as a possible mechanism in this process. Since NO attenuated the contractility to vasoconstricting agents such as norepinephrine (NE) by directly acting on the smooth muscle cells, this mechanism was considered mainly as a postsynaptic mechanism. In this research it was investigated whether NO, thus released, also participates in the presynaptic events for the regulation of vascular tone in endotoxic shock. The role of NO was studied by adding NO donors or NO synthase inhibitor $N^\omega $methyl-L-arginine (NMA) in stimulated sympathetic nerves of the mesenteric vascular bed and the Langendorff heart of rats. Sodium nitroprusside (SNP), an NO donor, reduced the pressor responses of isolated mesenteric artery either to electrical stimulation or exogenously administered phenylephrine (PE). In this mesentery, although neither agent influenced NE release, in the presence of the adrenergic $\alpha_2$-receptor antagonist yohimbine, elecrical stimulation-evoked NE release was augumented by SNP. In the heart SNP facilitated the NE release induced by electrical stimulation, while NMA had no effect. From these results it is proposed that there exists a local reflex phenomenon in the junction between the sympathetic nerve terminals and the smooth muscle of resistance blood vessels; by which sympathetic responses are reduced by NO at the postjunctional level while NO facilitates NE release contributing to augumentation of sympathetic tone. All these facts suggest that NO produced during endotoxic shock has dual effects: whereas NO blunts the vasoconstrictive activity of NE at the postsynaptic level, NO presynaptically facilitates the release of NE from sympathetic nerve terminals.

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  7. [국내논문]   Methanol이 배양된 흰쥐 해마의 신경세포 및 신경교 세포의 성장에 미치는 영향  

    이정임 (이안과 의원 ) , 조병채 (이화여자대학교 의과대학 안과학실 ) , 배영숙 (이화여자대학교 의과대학 약리학실 ) , 이경은 (이화여자대학교 의과대학 약리학실)
    한국독성학회지 = The Korean journal of toxicology v.12 no.2 ,pp. 203 - 211 , 1996 , 0258-2368 ,

    초록

    Methanol has been widely used as an industrial solvent and environmental exposure to methanol would be expected to be increasing. In humans, methanol causes metabolic acidosis and damage to ocular system, and can lead to death in severe and untreated case. Clinical symptoms are attributed to accumulation of forrnic acid which is a metabolic product of methanol. In humans and primates, formic acid is accumulated after methanol intake but not in rodents due to the rapid metabolism of methanol. Neverthless, the developmental and reproductive toxicity were reported in rodents. Previous reports showed that perinatal exposure to ethanol produces a variety of damage in human central nervous system by direct neurotoxicity. This suggests that the mechanism of toxic symptoms by methanol in rodents might mimic that of ethanol in human. In the present study I hypothesized that methanol can also induce toxicity in neuronal cells. For the study, primary culture of rat hippocampal neurons and glias were empolyed. Hippocampal cells were prepared from the embryonic day-17 fetuses and maintained up to 7 days. Effect of methanol (10, 100, 500 and 1000 mM) on neurite outgrowth and cell viability was investigated at 0, 18 and 24 hours following methanol treatment. To study the changes in proliferation of glial cells, protein content was measured at 7 days. Neuronal cell viability in culture was not altered during 0-24 hours after methanol treatment. 10 and 100 mM methanol treatment significantly enhanced neurite outgrowth between 18-24 hours. 7-day exposure to 10 or 100 mM methanol significantly increased protein contents but that to 1000 mM methanol decreased in culture. In conclusion, methanol may have a variety of effects on growing and differentiation of neurons and glial cells in hippocampus. Treatment with low concentration of methanol caused that neurite outgrowth was enhanced during 18-24 hours and the numbers of glial cell were increased for 7 days. High concentration of methanol brought about decreased protein contents. At present, the mechanism responsible for the methanol- induced enhancement of neurite outgrowth is not clear. Further studies are required to delineate the mechanism possibly by employing molecular biological techniques.

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  8. [국내논문]   만성 속발성 신질환 모델동물에서 콜라젠 변화의 지표   피인용횟수: 1

    남정석 (서울대학교 수의과대학 공중보건학실 ) , 김기영 (원광대학교 의과대학 병리학교실 ) , 이영순 (서울대학교 수의과대학 공중보건학실)
    한국독성학회지 = The Korean journal of toxicology v.12 no.2 ,pp. 213 - 221 , 1996 , 0258-2368 ,

    초록

    In order to develop a suitable secondary renal disease model and diagnostic markers of renal disease in the rat, the change of PIIIP (aminoterminal procollagen III peptide) in serum and hydroxyproline levels in the renal tissue that reflect the synthesis of extracellular matrix (ECM) during development of experimental renal diseases were observed. Two types of experimental primary diseases, diabetes mellitus administrated by streptozotocin (STZ, 75 mg/kg, i.p.) and liver cirrhosis produced by bile duct ligation/scission (BDL/s) operation, were induced. The hydroxyproline level increased according to the high PIIIP and NCl(carboxyterminal procollagen IV peptide) in Western blot analysis as early as 1 week in the STZ treated-rat kidney. Increased renal ECM was observed at 15 weeks in STZ and BDL/s model under the microscopic examination. High PAS positive reaction was found in capillary basement membrane in STZ treated-rats and mesangium in BDL/s operated rats at this time, showing the histological characteristics of diabetic nephropathy and cirrhotic glomerulonephritis in human, respectively. Such secondary renal failure were supported by additional tests including urinalysis and renal function test. The serum PIIIP detected by ELISA was a useful parameter to estimate synthesis rate of renal ECM during development of renal disease without extrarenal fibrosis i.e. liver cirrhosis in rats. This study is proposed that STZ treatment or BDL/s operation may be a suitable experimental animal model for the induction and development of chronic secondary renal diseases. Morover, it was found that hydroxyproline level in renal tissues was a good parameter of the change of renal ECM at the early stage of the diseases without apparent histological changes. Especially, serum PIIIP could be a choice as a diagnostic or prognostic marker during the development of renal diseases in rats.

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  9. [국내논문]   마우스에 있어서 Pyrimethamine과 Folic acid의 병용에 의한 태아독성 상승효과  

    정문구 (한국화학연구소 안정성연구센터 ) , 조규혁 (한국화학연구소 안정성연구센터 ) , 김종춘 (한국화학연구소 안정성연구센터 ) , 홍기창 (고려대학교 자연자원대학 ) , 한상섭 (한국화학연구소 안정성연구센터)
    한국독성학회지 = The Korean journal of toxicology v.12 no.2 ,pp. 223 - 230 , 1996 , 0258-2368 ,

    초록

    The increased embryotoxicity of the antifolate drug pyrimethamine (PYM) with concomitant dietary dosing of folic acid (FA) was examined in mice. The preventive effects of folinic acid (FNA) on PYM embryotoxicity were also examined. Six groups were constructed: PYM I (pyrimethamine 80 ppm), PYM II (pyrimethamine 150 ppm), PYM II+FNA (pyrimethamine 150 ppm and folinic acid 12 mg/kg/day), PYM II+FA (pyrimethamine 150 ppm and folic acid 350 ppm), FA (folic acid 350 ppm) and a control group. The agents were administered for 7 days from day 6 throughout 12 of gestation. PYM and FA were administered with mashed feed and FNA was intraperitoneally injected. The high incidence of fetal realformations was observed in the PYM II group; these included kinky tail, open eyelids, club foot, cleft palate, absence of the pulmonary lobe, diaphragmatic hernia, fused sternebrae, fused cervical or thoracic vertebral arch, among others. All embryos of the PYM II+FA group were resorbed. No realformed fetuses were observed in the PYM II+FNA group. These results show that the concomitant dosing of FA augments PYM embryotoxicity. The preventive effects of FNA were also observed.

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  10. [국내논문]   Diazinon, Toxaphene, Endrin과 그 혼합물의 독성효과  

    김종수 (경상대학교 수의과대학 ) , 하대식 (경남보건환경연구원 ) , 손성기 (경상남도 가축위생 시험소)
    한국독성학회지 = The Korean journal of toxicology v.12 no.2 ,pp. 231 - 236 , 1996 , 0258-2368 ,

    초록

    The toxicity of the mixture of diazinon, toxaphene(TOX) and/or endrin was studied in ICR male mice(18-22 g) by oral intubation, in corn oil, daily for up to 14 days. On day 15, the exposure was discontinued and animals were monitored for an additional period of 7 days for the possible reversibility of the toxicity. The body weight gain decreased with the mixtures, as well as with the individual pesticides, during the 14-day period. TOX and TOX containing mixtures significantly increased the liver/body weight ratio. The serum glutamic pyruvic transaminase level increased at 23~374% in diazinon, TOX, and endrin or their mixture group. The cholinesterase(ChE) activity in the serum and brain was inhibited in the animals of the group of diazinon(5, 10 mg/kg) and diazinon(5 mg/kg) containing mixtures. TOX(40, 80 mg/kg) caused initial inhibitory effects on the serum ChE Day 1. but there is little effects on the brain ChE levels. endrin(5,10 mg/kg) results in significantly elevated levels of the serum ChE, with substantial decreases in the brain ChE activity. TOX and TOX containing mixtures decreased the pentobarbital(60 mg /kg, ip., in saline) induced sleep. The effects produced by this pesticides singly, as well as by their mixtures, appeared to be reversible in nature. The toxic effects exhibited by the mixtures of diazinon(5 mf/kg), TOX(40 mg/kg), and /or endrin(5 mg/kg) were found to be the resultant of the effect showed by their components individually.

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