• Title/Summary/Keyword: acute-toxicity

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Effect of Geumsuyukgunjeon on Airway Mucus Secretion and Mucin Production (금수육군전(金水六君煎)이 이산화황으로 유발된 흰쥐의 호흡기 점액 및 뮤신생성에 미치는 영향)

  • Kim, Eun Jin;Min, Sang Yeon;Kim, Jang Hyun
    • The Journal of Pediatrics of Korean Medicine
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    • v.29 no.2
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    • pp.26-36
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    • 2015
  • Objectives In this study, effect of Geumsuyukgunjeon (GYJ) on the increase in airway epithelial mucosubstances of rats with acute bronchitis and EGF-induced MUC5AC mucin production from human airway epithelial cells were investigated. Materials and Methods Hypersecretion of airway mucus was induced by exposure of rats to SO2 during 3 weeks. Effect of orally-administered GYJ during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats was assesed using histopathological analysis after staining the epithelial tissue with PAS-alcian blue. Possible cytotoxicity of GYJ was assessed by examining the potential damage of kidney and liver functions by measuring serum GOT/GPT activities and serum BUN and creatinine concentrations of rats and the body weight gain during experiment, after administering GYJ orally. Effect of GYJ on EGF-induced MUC5AC mucin production from human airway epithelial cells (A549) was investigated. Confluent A549 cells were pretreated for 30 min in the presence of GYJ and treated with EGF (25 ng/ml) for 24 hrs, to assess the effect of GYJ on EGF-induced MUC5AC mucin production using enzyme-linked immunosorbent assay (ELISA). Results (1) GYJ decreased the amount of intraepithelial mucosubstances of trachea of rats. (2) GYJ did not show kidney and liver toxicities and did not affect body weight gain of rats during experiment. (3) GYJ significantly inhibited EGF-induced MUC5AC mucin production from A549 cells. Conclusions The result from the present study suggests that GYJ might control both the mucus hypersecretion in vivo and do not show in vivo toxicity to liver and kidney functions after oral administration and the production of pulmonary mucin.

Synthesis, Physicochemical Properties and Antitumor Activity of 5-Fluorouracil Prodrugs (5-플로우로우라실 프로드럭의 제조, 물리화학적 성질 및 항암효과)

  • Jee, Ung-Kil;Lee, Gye-Won
    • YAKHAK HOEJI
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    • v.40 no.3
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    • pp.279-292
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    • 1996
  • To assess their stability as a prodrug of 5-fluorouracil (5-FU), four N-acyloxycarbonyl derivatives (1-(N-tert-butyloxycarbonyl)glycyloxymethyl-5-FU :BGFU, 1-(N-tert-butyloxycar bonyl)-leucyloxymethyl-5-FU:BLFU, 1-(N-tert-carbobenzyloxymethyl) glycyloxymethyl-5-FU:CGFU and 1-(N-tert-carbobenzlyoxymethyl)leucyloxymethyl-5-FU:CLFU) possessing differently protected amino acids, and two acetic acid derivatives (5FU-1-acetylpentane:FUAP and 5-FU-1-acetylhexane:FUAH) were synthesized and their physicochemical properties, hydrolysis kinetics, acute toxicity and antitumor activity were evaluated. The lipid-water partition coefficients of six 5-FU prodrugs were higher than that of 5-FU and their aqueous solubilities were in the following rank order; BGFU>FUAP>CGFU>BLFU>CLFU${\simeq}$FUAH. The hydrolysis of N-acyloxycarboyl derivatives, greater at higher pH, was enhanced in presence of liver homogenate or human plasma. Meanwhile, acetic acid ester derivatives, very stable, were hydrolyzed by liver homogenate. Absorption rate constants were 0.181, 0.121, 0.111, 0.168, 0.168, 0.116 and 0.125 $hr^{-1}$ for 5-FU, BGFU, BLFU, CGFU, CLFU, FUAP and FUAH, respectively. The cytotoxicity of N-acyloxycarbonyl derivatives was 4 to 5 times lower than that of 5-FU, but that of acetic acid ester derivatives was negligeble. The $LD_{50}$ values were 204, 325.97 (133.59, amount as 5-FU), 708.16 (262.13), 663.50 (211.77), 382.33 (192.54) and 272.33 (130.09) mg/kg for 5-FU, BGFU, CGFU, CLFU, FUAP and FUAH, respectively. While N-acyloxycarbonyl derivatives showed enhanced antitumor activity and therapeutic ratio (3.30, 3.06, 4.19, 3.11 and 1.81 for BGFU, BLFU, CGFU, CLFU and 5-FU, respectively), FUAH and FUAP showed a smaller therapeutic ratio (0.79 and 0.83).

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Changes in Glucose Concentrations and Activities of Cholinesterase in Serum, Brain and Spinal cord in Mice following Orally Administration of Parathion (Parathion을 경구투여한 Mouse의 체내 Cholinesterase 활성도 및 Glucose함량 조사)

  • 도재철;이창우;차우양;손재권;정종식
    • Korean Journal of Veterinary Service
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    • v.15 no.1
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    • pp.58-66
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    • 1992
  • The insecticide p-nitropheny diethyl thiophospate is alse known by the symbol E.605 and a legion of trade names including “parathion”. The insecticide is widely used in agriculture, but it is highly toxic and now clear that parathion behaves like a cholinergic drug by inhibiting the enzyme cholinesterase. In order to know acute toxicity and the changes of glucose concentrations and activity according to time lapsed in female mice given orally single with the half dose to $LD_{50}$ of parathion, glucose contents and cholinesterase activities in serum as well as cholinesterase activities in whole brain and spinal cord were investigated, otherwise median lethal dose ($LD_{50}$) of parathion given orally against female mice was determined. The results obtained were summerized as follows ; 1. $LD_{50}$ value of parathion given orally to female mice was 7.1mg/kg(95% confidence limits, 3.8-13.1mg/kg) 2. The inhibition rate of cholinesterase activities in serum of parathion-administrated mice according to time lapsed were peakly decreased to 61% after 30 minutes in comparison to control group, but activities were completely recovered after 48 hours. 3. The inhibition rate of cholinesterase activities in whole brain of parathion-administrated mice according to time lapsed were peakly decreased to 49% after 2 hours in completely recovered after 24 hours. 4. The inhibition rate of cholinesterase activities in spinal cord of parathion-administrated mice according to time lapsed were peakly decreased to 57% after 2 hours in comparison to control group, but activities were completely recovered after 48 hours. 5. The changes of glucose contents in serum of parathion-administrated mice according to time lapsed and in directly after death due to parathion poisoning were no significantly difference.

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Effect of Continuous Exposure to Reactive Oxygen Species on ${\gamma}$-Glutamyltranspeptidase Expression and Activity in HepG2 Cells (HepG2 세포에서 지속적인 활성 산소 노출이 ${\gamma}$-Glutamyltranspeptidase 발현과 활성에 미치는 영향)

  • Kim, Young-Whan;Choe, Dal-Ung
    • Journal of Environmental Health Sciences
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    • v.30 no.3
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    • pp.230-238
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    • 2004
  • The adverse health effects of a number of environment pollutions are related to the formation of free radicals. Induction of antioxidant defensive system in the response to an oxidative attack is an essential element of the cell to survive. CYP2E1 is easily induced by organic solvents and induces continuous formation of reactive oxygen species (ROS). ${\gamma}$-Glutamyltranspeptidase (${\gamma}$GT) plays an important role in glutathione metabolism and xenobiotic detoxification. To evaluate the characteristic of oxidative stress which induces GGT expression and to understand human antioxidant defensive response against oxidative stress induced by CYP2E1, we studied regulation of ${\gamma}$GT enzyme expression in response to various oxidative stresses in human HepG2 cells. The ${\gamma}$GT activity was not modified after exposure of acute oxidative stress inducing agents (ferric nitrilotriacetate, cumene hydroperoxide, ADP-Fe, O-tetradecanoylphorbol-13-acetate, tumor necrosis factor-alpha). To induce continuous exposure of cells to ROS, HepG2 cells were transfected by human CYP2E1 gene transiently. The CYP2E1 activity was verified with chlorzoxazone hydroxylation. Transfection of CYP2E1 showed continuous 60% increase in intracellular ROS and 240 % increase in microsomal ROS. CYP2E1 overexpressing cells showed increased ${\gamma}$GT activity (2.5-fold). The observed enhancement of ${\gamma}$GT activity correlated with a significant increase of ${\gamma}$GT mRNA (2.1-fold). Treatment with antioxidant strongly prevented the increase in ${\gamma}$GT activity. The CYP2E1 overexpression did not modify toxicity index and increased glutathione levels. These results show that continuous exposure of cells to ROS produced by CYP2E1 up-regulates ${\gamma}$GT; This may be one of the adaptive antioxidant responses of cells to oxidative insult. Present study also suggests that the induction of ${\gamma}$GT could be used as a marker of oxidative stress induced by exposure to organic solvents.

Effect of Kalopanaxii Cortex Extract on Experimentally Induced Liver Damage in Rabbits (해동피추출물이 실험적으로 유발된 가토의 간장기능장애에 미치는 영향)

  • Jun, Sung-Joo;Sheo, Hwa-Joong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.18 no.3
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    • pp.273-278
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    • 1989
  • This study was carried out to investigate effects of Kalopanaxii Cortex extract(K. C. E,) on $CCI_4$-induced liver damage in rabbits and acute toxicity in mice. 1. $LD_{50}(mg/kg)$ of K. C. E. was 7.3g/kg by intraperitoneal administration in mice. 2. K. C. E. groups showed more rapid recovery than the control group in $CCI_4$-intoxicated rabbits and 800mg/kg was the most effective. 3. SGPT and alkaline phosphatase activity showed and apparent decreasing effect within 14 days and 2 days respectively in 800mg/kg. 4. The levels of total cholesterol and total bilirubin showed and apparent decreasing effect within 10 days and 6 days respectively in 800mg/kg. It is suggested that K. C. E. can be administered not only as a therapeutic agent but also a healthy food to shorten the recovery time of hepatic function in liver diseases.

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Protective Effects of Food Including Hovenia dulcis on Acute Alcohol Intoxication (급성 알코올 중독에서 헛개나무 추출물을 포함한 식품 조성물의 보호 효과)

  • Choi, Geun-Ho;Kim, Jong-Gwan;Kwon, Seoung-Taek
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.8
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    • pp.1107-1112
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    • 2011
  • Over-consumption of alcohol leads to many side-effects such as malnutrition, liver disease, and neuronal disorders and many investigators have tired to identify methods for preventing the side-effects of drinking. In this study, we demonstrated the protective effect of a new food component, SAC-1, containing Hovenia dulcis Thumb and Lonicera caerulea Thumb extract against the side-effects of drinking. We observed that blood alcohol concentration, glutamic oxaloacetate transaminase, lipid peroxidation, and total glutathione level decreased significantly in plasma and liver of mice fed the SAC-1 extract before alcohol intoxication. In particular, SAC-1 had more of a protective effect than that of Hovenia dulcis Thumb extract alone. These results suggest that SAC-1 should further be developed to treat alcohol detoxification and stimulate antioxidative potentials.

Anxiolytic effect of leaf galls extracts of Pipernigrum Linn. in Swiss Albino mice

  • Rajesh, R;Sathiyanarayanan, L;Arulmozhi, S;Ruby, Ruby
    • Advances in Traditional Medicine
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    • v.9 no.2
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    • pp.142-148
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    • 2009
  • Anxiety disorders are one of the serious problems which need proper therapy devoid of side effects of presently available medicines. The present study evaluates the anxiolytic and sedative activity of leaf galls of Piper nigrum Linn. in Swiss Albino mice. The pet. ether, chloroform, ethyl acetate and ethanol extracts of leaf galls of Piper nigrum Linn were obtained by continuous soxhlet extraction. The prepared extracts were found to be safe up to 2000 mg/kg body weight of mice in the acute toxicity study. Each extract was assessed for anxiolytic activity in Swiss Albino mice by elevated plus Maze, open field test, rota rod test and phenobarbitone induced sleeping time test. In the Elevated Plus Maze test, the pet.ether extract and chloroform extract at a dose of 50 mg/kg b.w. orally, significantly (P < 0.01) increased the number of entries and time spent in open arm comparable with standard diazepam at the dose of 10 mg/kg. b.w. p.o. In the open field test, pet. ether extract (50 mg/kg b.w. p.o.) showed significant increase (P < 0.01) in ambulation and activity in the center. Chloroform extract (50 mg/kg b.w p.o.) was significant (P < 0.05) for both ambulation and center activity. Pet. ether extract (50 mg/kg b.w. p.o) also showed significant activity (P < 0.01) in rota rod test. All the results are comparable with standard diazepam at the dose of 1 mg /kg b.w, p.o. Moreover all the extracts showed significant (P < 0.01) increase in the phenobarbitone induced sleeping time among which pet.ether showed more prominent activity (36%) comparable with control. The results revealed that, the active pet.ether extract and chloroform extract of leaf galls of Piper nigrum Linn is worthwhile to develop the bioactive principle for anxiolytic activity.

The Fate and Factors Determining Arsenic Mobility of Arsenic in Soil-A Review

  • Lee, Kyo Suk;Shim, Ho Young;Lee, Dong Sung;Chung, Doug Young
    • Korean Journal of Soil Science and Fertilizer
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    • v.48 no.2
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    • pp.73-80
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    • 2015
  • Arsenic which is found in several different chemical forms and oxidation states and causes acute and chronic adverse health effects is a toxic trace element widely distributed in soils and aquifers from both geologic and anthropogenic sources. Arsenic which has a mysterious ability to change color, behavior, reactivity, and toxicity has diverse chemical behavior in the natural environment. Arsenic which has stronger ability to readily change oxidation state than nitrogen and phosphorus due to a consequence of the electronic configuration of its valence orbitals with partially filled states capable of both electron donation and acceptance although the electronegativity of arsenic is greater than that of nitrogen and similar to that of phosphorus. Arsenate (V) is the thermodynamically stable form of As under aerobic condition and interacts strongly with solid matrix. However, it has been known that adsorption and oxidation reactions of arsenite (III) which is more soluble and mobile than As(V) in soils are two important factors affecting the fate and transport of arsenic in the environment. That is, the movement of As in soils and aquifers is highly dependent on the adsorption-desorption reactions in the solid phase. This article, however, focuses primarily on understanding the fate and speciation of As in soils and what fate arsenic will have after it is incorporated into soils.

An Outer Membrane Protein Preparation as a Vaccine against Pseudomonas aeruginosa Infection

  • Park, Wan-Je;Cho, Yang-Je;Ahn, Dong-Ho;Jung, Sang-Bo;Lee, Na-Gyong;Kim, Hyun-Su;Hahm, Kyung-Soo;Kim, Yu-Sam
    • Journal of Microbiology and Biotechnology
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    • v.7 no.2
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    • pp.144-150
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    • 1997
  • We developed a simple and efficient method to prepare a Pseudomonas vaccine of outer membrane (OM) proteins free from lipopolysaccharide (LPS). A three step purification process including extraction, ultrafiltration and ultracentrifugation effectively removed LPS from the OM protein fraction. Approximately 2 mg of the OM proteins was obtained from 1 g of wet cell. LPS contaminant in the vaccine preparation was less than 0.003% (w/w) of protein and protease activity was not detectable. To achieve a wide range of protection, OM proteins prepared from four attenuated P. aeruginosa strains were mixed in equal amounts and used as a vaccine, which elicited in rabbits a high titer of antibody reactive to all of the seven Fisher types. The antisera from the immunized rabbit had a strong reactivity to vaccine proteins larger than 25 kDa. In a burned mouse infection model, immunization with the vaccine significantly enhanced bacterial clearance in the Pseudomonas infected skin. The vaccination also provided mice an excellent protection against Pseudomonas infection (11, 16). Data on antigenicity, mutagenicity, acute, subacute toxicity and pharmacological tests confirmed the safety of the vaccine (1, 3, 10, 12, 17). These data demonstrate that this method can be applied to manufacture a bacterial vaccine of OM proteins with safety and prophylactic efficacy at a practical low cost.

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Efficacy of Three Different Plant Species for Arsenic Phytoextraction from Hydroponic System

  • Tiwari, Sarita;Sarangi, Bijaya Ketan;Pandey, Ram Avatar
    • Environmental Engineering Research
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    • v.19 no.2
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    • pp.145-149
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    • 2014
  • Arsenic (As) is one of the heavy metals which causes acute bio-toxicity even at low concentration and has disastrous effect on environment. In some countries, As contamination has become alarming and increasing day by day as consequences of unsustainable management practices. Many existing physical, chemical and biological processes for As removal from water system are not feasible due to techno-economic limitations. The present study highlights the scope of biological strategy for As removal through phytoextraction. Arsenic uptake and accumulation in the biomass of three plant species and their As tolerance abilities have been investigated to develop an efficient phytoextraction system in combination of these plant species. Three non-crop plant species, Pteris vittata; Mimosa pudica, and Eichhornia crassipus were treated with 0-200 mg/L As in liquid nutrient solution for 14 days. P. vittata accumulated total 9,082.2 mg (8,223 mg in fronds) As/kg biomass and Eichhornia total 6,969 mg (4,517 mg in fronds)/kg biomass at 200 mg/L As concentration, respectively. Bioaccumulation factor (BF) and translocation factor (TF) were estimated to differentiate between excluders, accumulators and accumulation in above ground biomass. Pteris and Eichhornia have highest BF (67 and 17) and TF (64 and 3), respectively. In contrast, Mimosa accumulated up to 174 mg As/kg plant biomass which is low in comparison with other two plants, and both BF and TF were ${\leq}1$. This study reveals that Pteris and Eichhornia are As hyperaccumulator, and potential candidates for As removal from water system.