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새로운 Cephalosporin계 항생제 IDC-7181의 랫드에 대한 단회 및 4주반복 정맥투여 독성시험
장호송,황재식,신장우,정은용,신지순,이수해,이종성,강재훈,김기원,김윤배,남상윤,강종구 한국독성학회 2002 Toxicological Research Vol.18 No.2
This study was performed to evaluate single and repeated-dose toxicities of a new cephalosporin antibiatic agent IDC-7181 in Sprague-Dawley rats. IDC-7181 was injected intravenously to rats at dose levels of 0, 3.2, 16, 80, 400 and 2,000 mg/kg/day for single-dose toxicity study and at dose levels of 0, 10, 50 and 250 mg/kg/day for 4-week repeated-dose toxicity study. In both stduies, there were no dose-related changes in mortality, clinical signs, body weight changes, food and water consumption, opthalmoscpy, organ weights, urine analysis, biochemical examination, and hematological findings of all animals treated with IDC-7181. Gross and histopathological findings revealed no evidence of specific toxicity related to IDC-7181. These results suggest that the intravenouse maximum tolerated dose value of IDC-7181 may be over 250 mg/kg and LD_(50) value may be over 2,000 mg/kg in rats.
마우스에서 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD)에 의해 유발된 간독성에 대한 웅담의 방어효과
장호송,남상윤,강종구,Zhang, Hu-Song,Nam, Sang-Yoon,Kang, Jong-Koo 한국생약학회 2001 생약학회지 Vol.32 No.2
The effect of bear bile on 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD)-induced hepatotoxicity was investigated in 6-week-old C57BL/6 male mice. Bear bile (100 mg/kg or 500 mg/kg) was administered orally daily for 4 weeks, respectively. From the second week, $10\;{\mu}g/kg$ of TCDD was administered to the bear bile-treated animals orally once a week for 3 weeks (a total of $30\;{\mu}g/kg$). There were no specific clinical findings and significant body weight changes in all groups. Although the livers in TCDD-treated mice appeared a severe hypertrophy and many necrotic foci, and changed to yellow-brown color in gross findings, these lesions were remarkably reduced by bear bile administration. The elevated serum activities of alanine transaminase, aspartate transaminase, alkaline phosphatase, and lactate dehydrogenase due to TCDD were significantly decreased by bear bile treatment (P<0.05). The lipid peroxidation induced by TCDD was significantly prevented by bear bile administration (P<0.05). In histological examinations, there were a moderate necrosis of hepatic cells around central veins, severe cytoplasmic vacuolizations, inflammatory cell infiltrations, and remarkable fatty changes in the liver of TCDD-treated animals. However, the lesions were dose-dependently inhibited by the bear bile treatments. These findings indicate that bear bile may have a protective effect against TCDD-induced hepatotoxicity in mice.
새로운 Anthracycline계 항암제 Hyrubicin ID6105에 대한 유전독성연구
장호송,정미숙,이홍섭,유정수,김태영,김윤배,강종구 한국독성학회 2002 Toxicological Research Vol.18 No.4
The genotoxic potential of Hyrubicin ID6105, a novel anthracycline anticancer agent, was examined on bacterial mutagenicity, mammalian cell chromosome aberration and mouse micronucleus tests. In mutagenicity (Ames'') test, Salmonella typhimurium strain TA98, TA100, TA1535 and TA1537, and Escherichia coli WP2uvrA^- were treated with ID6105 at doses of 312.5, 625, 1,250, 2,500 and 5,000㎍/plate with or without a metabolic activation system (S9 mix). Interestingly, ID6105 significantly enhanced the number of revertant colonies of TA98 strain at all dose levels used, in the presence or absence of S9 mix, without affecting other strains of S. typhimurium and E. coli, In chromosome aberration test using cultured chinese hamster lung fibroblasts, ID6105 (1.25, 2.5 and 5㎍/ml) did not increase the number of aberrant cells, compared with vehicle control, in the presence or absence of S9 mix. In addition, ID6105 treatment (2.5, 5 and 10 mg/kg) did not induce micronucleated polychromatic erythrocytes in mice. Taken together, it is suggested that ID6105 might not affect chromosome integrity in mammalian systems in vitro and in vivo, although it may induce frame shift mutation of specific bacterial strain such as S. typhimurium TA98.
랫드에서 새로운 Anthracycline계 항암제 Hyrubicin ID6105에 대한 4주 반복투여 독성연구
장호송,서동석,인창훈,황재식,이수해,정미숙,신지순,이홍섭,유정수,김태영,김윤배,강종구 한국독성학회 2002 Toxicological Research Vol.18 No.4
Repeated-dose toxicity of hyrubicin ID6105, a novel anthracycline anticancer agent, was investigated in Sprague-Dawley rats. ID6105 was injected intravenously to rats at dose levels of 0.04, 0.2 or 1.0 mg/kg/day for 4 weeks. As a result, there were no dose-related mortality and specific clinical signs of all animals treated with the drug. However, body weight gain of both male and female rats treated with a high dose (1.0mg/kg/day) of ID6105 significantly decreased compared to control. Interestingly, the numbers of RBC and platelets, and concentration of hemoglobin remarkably increased, while protein synthesis was suppressed, which may be related to the atrophy of spleen, thymus and liver. Moreover, there were severe lymphocytic depletion in spleen and thymus as well as decrease in the number of hematopoletic cells in bone marrow. Also, degeneration of cardiac muscles and testicular germinal epithelia were observed. Taken together, it is suggested that long-term administration of ID6105 at high doses over 0.2mg/kg/day might cause hematopoietic and male reproductive system injuries, in addition to hepatic dysfunction.
YHB216 의 비글개에서 정맥내 단회 및 4 주 반복투여독성시험
장호송(Hu Song Zhang),정은용(Eun Yong Jung),신지순(Ji Soon Sin),안경규(Kyoung Kyu Ahn),최연식(Yeon Shik Choi),강종구(Jong Koo Kang),노용우(Yong Woo Roh),지형진(Hyeong Jin Ji),강민정(Min Joung Kang),이종욱(Jong Wook Lee) 한국응용약물학회 2002 Biomolecules & Therapeutics(구 응용약물학회지) Vol.10 No.1
N/A Recently, recombinant human erythropoietin (rHu-EPO) has been used to treat various types of anemia. YHB216 is a new rHu-EPO developed by Yuhan Research Institute. In this study, we investigated the single dose and 4-week repeated dose toxicity of YHB216 in Beagle dogs. In the single dose toxicity study, YHB216 was administered intravenously at single dose levels of 0 and 25,000 IU/㎏ to dogs (2 dogs/sex/ group). There were no treatment-related changes in survivals, clinical signs, body weight gain, hematological values, blood chemical values, and necropsy finding during experimental period. In the repeated dose toxicity study, YHB216 was administered intravenously to dogs for 4 weeks at the dose levels of 0, 100, 500, and 2,500 IU/㎏ (3 dogs/sex/group). There were no toxicologically significant changes in clinical signs, body weights, food and water consumptions, ophthalmoscopy, urinalysis and blood chemistry. There were increased values of red blood cell, hemoglobin, and hematocrit at all treated groups. Spleen revealed increased weight and extramedullary hematopoiesis at 500 IU/㎏ or more. These changes are all considered to be pharmacology-related effects and were recovered after 4-week recovery period. From these results, it is concluded that LD_50 value was above 25,000 IU/㎏ in the single dose toxicity study of YHB216 in dogs and the no observed adverse effect level (NOAEL) was 100 IU/㎏/day in the repeated dose toxicity study of YHB216 in dogs.
금은화(Flos lonicerae) 추출물의 Fischer 344/N 랫드를 이용한 90일간 반복 경구투여 독성시험
한충택,장호송,강상철,길기현,공광한,김도형,안태환,배진숙,고현규,한명규,김학수,허현숙,박은미,송시환,김갑호,박찬구,이현걸,Han, Zhong-Ze,Zhang, Hu-Song,Kang, Sang-Chul,Gil, Ki-Hyun,Kong, Kwang-Han,Kim, Do-Hyung,Ahn, Tae-Hwan,Bae, Jin-Sook,Go, Hyeon-Kyu,Ha 대한수의학회 2008 大韓獸醫學會誌 Vol.48 No.4
This study was performed to evaluate repeated-dose oral toxicities of Flos lonicerae extract in Fischer 344/n rats. Flos lonicerae was administered orally to rats at dose levels of 0, 37, 111, 333, 1,000 and 2,000 mg/kg/day. Each group consisted of 10 rats of each gender. The Flos lonicerae extract was given once a day, 5 times a week, for 90 day repeatedly. This study was conducted in accordance with the Protocol of Korea National Toxicology Program and The Standards of Toxicity Study for Medicinal Products. In the present study, there were no toxicologically significant changes in mortality, clinical signs, body weight gains, ophthalmoscopy, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histopathology, estrus cycle and sperm examination of all animals treated with Flos lonicerae extract. These results suggest that the oral no observed adverse-effect level of the test item, Flos lonicerae extract, in rats is higher than 2,000 mg/kg/day in both genders. The target organs were not established.
백굴채(Chelidonium majus) 추출물의 Fischer 344/N 랫드를 이용한 90일간 반복 경구투여 독성시험
김도형,장호송,김광호,강상철,김학수,길기현,공광한,안태환,배진숙,고현규,김갑호,박찬구,이현걸,송시환,한충택,Kim, Do-Hyung,Zhang, Hu-Song,Kim, Kwang-Ho,Kang, Sang-Chul,Kim, Hak-Soo,Gil, Ki-Hyun,Kong, Kwang-Han,Ahn, Tae-Hwan,Bae, Jin-Sook,Go, Hyeon-K 대한수의학회 2009 大韓獸醫學會誌 Vol.49 No.1
This study was performed to evaluate repeated-dose oral toxicities of Chelidonium majus extract in Fischer 344/N rats. Chelidonium majus extract was administered orally to rats at dose levels of 0, 25, 74, 222, 666 and 2,000 mg/kg/day. Each group consisted of 10 rats of each gender. The Chelidonium majus extract was given once a day, 5 times a week, for 90 day repeatedly. This study was conducted in accordance with the Protocol of Korea National Toxicology Program (issued by National Institute of Toxicological Research) and The Standards of Toxicity Study for Medicinal Products (issued by Korea Food and Drug Administration). In the present study, There were no toxicologically significant changes in mortality, clinical signs, body weight gains, ophthalmoscopy, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histopathology, estrus cycle and sperm examination of all animals treated with Chelidonium majus extract. These results suggest that the oral no observed adverse-effect level of the test item, Chelidonium majus extract, in rats is higher than 2,000 mg/kg/day in both genders. The target organs were not established.
Cephalosporin계 항생제 IDC7181에 대한 항원성시험
신지순(Ji Soon Sin),장호송(Hu-Song Zhang),최은경(Ehn-Kyoung Choi),권운(Woon Kwon),채희열(Hee-Youl Chai),조영민(Young Min Cho),김윤배(Yun-Bae Kim),강종구(Jong-Koo Kang) 한국독성학회 2003 Toxicological Research Vol.19 No.4
Antigenic potential of a novel cephalosporin, IDC7181 was examined a active systemic anaphylaxis (ASA) and passive cutaneous anaphylaxis (PCA) test, in guinea pig and mouse-rat models, respectively. In ASA test, IDC7181 induced the signs of restlessness in a few animals immunized with a high dose (100 mg/kg) of IDC7181 alone or in combination with Freund's complete adjuvant (FCA). In PCA test, only one of ten sera from the animals immunized with a high dose (100 mg/kg) of IDC7181 in the absence or presence of FCA showed positive reaction. The positive reaction,<br/> induced by IDC7181, which may be due to β-lactam ring, in ASA and PCA tests were negligible in comparison with those of traditional cephalosporins. Taken together, it is suggested that IDC7181 do<br/> not cause immunological problems in clinical dosage.