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A 90-day repeated-dose oral toxicity study on Flos lonicerae extract in Fischer 344/N rats
2008
Han, Zhong-Ze (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Zhang, H.S. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Kang, S.C. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Gil, K.H. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Kong, K.H. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Kim, D.H. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Ahn, T.H. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Bae, J.S. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Go, H.K. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Han, M.K. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Kim, H.S. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Heo, H.S. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Park, E.M. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Song, S.W. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Kim, K.H. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Park, C.K. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea) | Lee, H.K. (Preclinical Research Center, ChemOn, Yongin, Republic of Korea), E-mail: leehk@chemon.co.kr
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.
اظهر المزيد [+] اقل [-]Effect of repeated Paecilomyces japonica treatment on rats
2014
Kim, Y.B., Korea Institute of Toxicology, Daejeon, Republic of Korea | Hong, D.H., Chungnam, National University, Daejeon, Republic of Korea | Cho, E.S., Chungnam, National University, Daejeon, Republic of Korea | Im, W.J., Korea Institute of Toxicology, Daejeon, Republic of Korea | Kim, I.H., DAEWOONG Pharmaceutical Co., Yongin, Republic of Korea | Son, H.Y., Chungnam, National University, Daejeon, Republic of Korea
Cordyceps is a fungus used as a traditional medicine in China, Japan, and Korea. Paecilomyces (P.) japonica is a new cordyceps that was recently cultivated on silkworm pupae in Korea. The present study evaluated the toxicological effects of P. japonica in rats. Forty rats were treated with oral doses of P. japonica (0, 20, 100, or 500 mg/kg/day) for 4 weeks. Twenty additional rats were treated with 0 or 500 mg/kg/day of P. japonica for 4 weeks and then maintained for 2 weeks without treatment. Clinical signs, body weight, food and water consumption, and organ weight as well as hematology, serum biochemistry, and histopathology data were examined. Body weight gain of the group treated with 500 mg/kg/day was significantly reduced. Microscopically, karyomegaly, single cell necrosis, and mitosis were observed in the renal tubular epithelium of all treated groups. In conclusion, P. japonica caused a reduction of body weight and renal injury in rats. The no observed adverse effect level (NOAEL) of P. japonica was less than 20 mg/kg/day.
اظهر المزيد [+] اقل [-]Flurbiprofen toxicity in 2 dogs
2013
Lee, Y., Seoul National University, Seoul, Republic of Korea | Nam, E.H., Seoul National University, Seoul, Republic of Korea | Park, S.H., Seoul National University, Seoul, Republic of Korea | Song, C.Y., Seoul National University, Seoul, Republic of Korea | Lee, Y.U., Seoul National University, Seoul, Republic of Korea | Lee, J.M., Seoul National University, Seoul, Republic of Korea | Park, J.H., Seoul National University, Seoul, Republic of Korea | Hwang, C.Y., Seoul National University, Seoul, Republic of Korea
Two dogs were presented with melena, vomiting and depression after accidental swallowing of candy form of Strepsils (flurbiprofen), which is one of non-steroidal anti-inflammatory drugs used in human medicine for controlling a sore throat. These dogs had common signs of anemia induced by gastrointestinal ulceration and hemorrhage with azotemia and leukocytosis. The dogs were treated with blood transfusion, fluid therapy, proton-pump inhibitor, antiemetics, mucus protectant and antibiotic. Although most of clinical signs of two dogs were resolved, azotemic problem with evidence of renal injury have remained.
اظهر المزيد [+] اقل [-]Oxidative Stress in C100 Cells Induced by Combined Treatment of Benzo(a)pyrene and/or 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD)
Bae, M.O.;Choi, K.H.;Lee, H.J.;Kim, H.W.;Kim, J.S.;Hwang, S.K.;Park, J.H.;Cho, H.S.;Cho, M.H.(Seoul National University, Seoul, Republic of Korea)E-mail:mchotox@snu.ac.kr
When an organism is exposed to various toxicants chronically, reactive oxygen species(ROS) are accumulated and eventually result in several biological effects from gene expression to cell death. In the present study we investigated the oxidative damage of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin(TCDD) and/or benzo(a)pyrene (B(a)P) in C100 cells. C100 cells treated with TCDD(30 nM) and B(a)P(3 μM) underwent diverse oxidative stress as determined through thiobarbituric acid-reactive substances(TBARS) formation, DNA fragmentation, DNA single strand break(SSB) assay, immunohistochemical staining of 8-hydroxy-2'-deoxyguanosine(8-OHdG), and mRNA expressions of antioxidant enzymatic genes such as Cu/Zn-SOD gene, GPx(glutathione peroxidase 5) gene, and catalase gene.
اظهر المزيد [+] اقل [-]Evaluation of thermally cross-linked superparamagnetic iron oxide nanoparticles for the changes of concentration and toxicity on tissues of Sprague-Dawley rats
2014
Hue, J.J., Chungbuk National University, Cheongju, Republic of Korea | Lee, H.J., Gyeongsang National University, Jinju, Republic of Korea | Jon, S.Y., School of Life Science, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea | Nam, S.Y., Chungbuk National University, Cheongju, Republic of Korea | Yun, Y.W., Chungbuk National University, Cheongju, Republic of Korea | Kim, J.S., Chungbuk National University, Cheongju, Republic of Korea | Lee, B.J., Chungbuk National University, Cheongju, Republic of Korea
This study was investigated the change of concentration and toxicity of thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) on tissues of Sprague-Dawley rats. TCL-SPION at the dose of 15 mg/kg body weight was intravenously injected into the tail vein of the male Sprague-Dawley rats. The fate of TCL-SPION in serum, urine and tissues was observed during 28 days. Serum iron level was maximal at 0.25 h post-injection and gradually declined thereafter. In addition, the sinusoids of liver and the red pulp area of spleen were mainly accumulated iron from 0.5 h to 28-day post-injection. In kidney, iron deposition was detected in the tubular area until 0.5 h after injection. Malondialdehyde concentration in the liver slightly increased with time and was not different with that at zero time. In the liver and spleen, TNF-¥�and IL-6 levels of TS treated with TCL-SPION were not different with those of the control during the experimental period. From the results, TCL-SPION could stay fairly long-time in certain tissues after intravenous injection without toxicity. The results indicated that TCL-SPION might be useful and safe as a contrast for the diagnosis of cancer or a carrier of therapeutic reagents to treat diseases.
اظهر المزيد [+] اقل [-]Differential gene expression pattern in brains of acrylamide-administered mice
2012
Han, C.H., Jeju National University, Jeju, Republic of Korea
The present study was performed to evaluate the relationship between the neurotoxicity of acrylamide and the differential gene expression pattern in mice. Both locomotor test and rota-rod test showed that the group treated with higher than 30 mg/kg/day of acrylamide caused impaired motor activity in mice. Based on cDNA microarray analysis of mouse brain, myelin basic protein gene, kinesin family member 5B gene, and fibroblast growth factor (FGF) 1 and its receptor genes were down-regulated by acrylamide. The genes are known to be essential for neurofilament synthesis, axonal transport, and neuro-protection, respectively. Interestingly, both FGF 1 and its receptor genes were down-regulated. Genes involved in nucleic acid binding such as AU RNA binding protein/enoyl-coA hydratase, translation initiation factor (TIF) 2 alpha kinase 4, activating transcription factor 2, and U2AF 1 related sequence 1 genes were down-regulated. More interesting finding was that genes of both catalytic and regulatory subunit of protein phosphatases which are important for signal transduction pathways were down-regulated. Here, we propose that acrylamide induces neurotoxicity by regulation of genes associated with neurofilament synthesis, axonal transport, neuro-protection, and signal transduction pathways.
اظهر المزيد [+] اقل [-]A 90-day repeated-dose oral toxicity study on Chelidonium majus extract in Fischer 344/N rats
2009
Kim, D.H., Preclinical Research Center, ChemOn, Yongin, Republic of Korea | Zhang, H.S., Preclinical Research Center, ChemOn, Yongin, Republic of Korea | Kim, K.H., Preclinical Research Center, ChemOn, Yongin, Republic of Korea | Kang, S.C., Preclinical Research Center, ChemOn, Yongin, Republic of Korea | Kim, H.S., Preclinical Research Center, ChemOn, Yongin, Republic of Korea | Gil, K.H., Preclinical Research Center, ChemOn, Yongin, Republic of Korea | Kong, K.H., Preclinical Research Center, ChemOn, Yongin, Republic of Korea | Ahn, T.H., Preclinical Research Center, ChemOn, Yongin, Republic of Korea | Bae, J.S., Preclinical Research Center, ChemOn, Yongin, Republic of Korea | Go, H.K., Preclinical Research Center, ChemOn, Yongin, Republic of Korea | Kim, K.H., Preclinical Research Center, ChemOn, Yongin, Republic of Korea | Park, C.K., Preclinical Research Center, ChemOn, Yongin, Republic of Korea | Lee, H.K., Preclinical Research Center, ChemOn, Yongin, Republic of Korea | Song, S.W., Preclinical Research Center, ChemOn, Yongin, Republic of Korea | Han, Z.Z., Preclinical Research Center, ChemOn, Yongin, Republic of Korea
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.
اظهر المزيد [+] اقل [-]Acute and subacute toxicity of trichlorfon in guppies (Poecilia reticulata)
2009
Heo, G.J., Chungbuk National University, Cheongju, Republic of Korea | Shin, G.W., Chonbuk National University, Jeonju, Republic of Korea
The aim of the present study was to determine the acute and subacute potential of trichlorfon in guppies (Poecilia reticulata). We first defined the 24h median tolerance limit (TLm∧24h) of the fish to trichlorfon. Guppies were then treated with TLm∧24h and 1/10 TLm∧24h trichlorfon concentrations to evaluate of any histological alterations occurred. The TLm∧24h value of trichlorfon was 11 ppm. This concentration resulted in acute toxicity to the gills and kidneys with edema, hyperplasia of the gill lamellae, and vacuolated degeneration and necrosis of renal tubular cells. In the case of subacute toxicity using a 10-fold dilution of the TLm∧24h value (1.1 ppm), no behavioral changes, external lesions or histopathological changes were observed. Therefore, safe concentration of trichlorfon might be 1.1 ppm in guppy for controlling parasitic infections.
اظهر المزيد [+] اقل [-]Toxicological effects of perfluorooctanoic acid in rats
2008
Kim, Y.H. (Chungnam National University, Daejeon, Republic of Korea) | Cho, E.S. (Chungnam National University, Daejeon, Republic of Korea) | Kim, A.Y. (Chungnam National University, Daejeon, Republic of Korea) | Kim, S.H. (Chungnam National University, Daejeon, Republic of Korea) | Park, M.S. (Chungnam National University, Daejeon, Republic of Korea) | Cho, S.W. (Chungnam National University, Daejeon, Republic of Korea) | Ryu, S.Y. (Chungnam National University, Daejeon, Republic of Korea) | Jung, J.Y. (Chungnam National University, Daejeon, Republic of Korea) | Son, H.Y. (Chungnam National University, Daejeon, Republic of Korea), E-mail: hyson@cnu.ac.kr
Perfluorooctanoic acid (PFOA), a member of the perfluoroalkyl acids that have wide commercial applications, is persistent organic pollutants widely spread throughout the environment and human population. But little is known about the adverse biological effects of the PFOA. In the present study, the toxicological effects of PFOA were investigated in rats. Sprague-Dawley rats (N = 10 in each group) were orally administered with PFOA in drinking water for 4 weeks (0, 100, 200, or 400 ppm in male, and 0, 200, 400, or 800 ppm in female). These female rats given 800 ppm died during the study. PFOA treatment decreased the body weight gain and increased the liver weights in both genders. Serum biochemical investigations revealed significant increases in the aspartate aminotransferase, alanine transaminase, alkaline phosphatase, blood urea nitrogen, total cholesterol, and total bilirubin in male but in female. Serum estradiol (E2) levels were increased in all treated in all treated rats. Histopathologically, hepatocellular hypertrophy around central vein was noted in the liver of treated rats. No significant histopathological change were noted in other organs. In conclusion, PFOA induced toxicological changes in the liver and increased serum E2 level which was not related to histopathological changes of endocrine and reproductive system.
اظهر المزيد [+] اقل [-]Subacute toxicological study of PG102, a water-soluble extract derived from Actinidia arguta, in SD rats
2008
Hong, E.S. (Helixir Co., Seoul, Republic of Korea) | Kim, M.J. (Helixir Co., Seoul, Republic of Korea) | Kwon, E.J. (Helixir Co., Seoul, Republic of Korea) | Kim, L.H. (Seoul National University, Seoul, Republic of Korea) | Kim, D.H. (Seoul National University, Seoul, Republic of Korea) | Eo, H.K. (Helixir Co., Seoul, Republic of Korea) | Park, E.J. (Helixir Co., Seoul, Republic of Korea) | Kim, S.Y. (Seoul National University, Seoul, Republic of Korea) | Kim, S.H. (Helixir Co., Seoul, Republic of Korea), E-mail: seonhee@helixir.co.kr
It was previously found that PG102, a water-soluble extract derived from Actinidia arguta, was able to modulate Th1/Th2 pathways and suppress IgE production resulting in dramatic amelioration of atopic dermatitis in NC/Nga mouse and hairless rat models. In order to evaluate the subacute toxicity of PG102, female and male SD rats were daily fed with various doses of PG102 for 4 weeks. Six week old SD rats were randomly divided into 4 groups and orally administrated with 100-, 300-, and 1,000-mg/kg of PG102 as well as the vehicle only. At the end of the study, no significant differences in the body and organ weights were observed between control and treated rats of both genders. Hematological and blood chemical analysis showed little differences between the animal groups. Neither gross abnormalities nor histopathological changes were found. PG102 produced little or no subacute toxicity and could be used as a safe nutraceutical for the treatment of individuals with allergic diseases including atopic dermatitis.
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