• YAKHAK HOEJI
• /
• v.40 no.3
• /
• pp.279-292
• /
• 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).

• Korean Journal of Veterinary Service
• /
• v.15 no.1
• /
• pp.58-66
• /
• 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.

• Journal of Environmental Health Sciences
• /
• v.30 no.3
• /
• pp.230-238
• /
• 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.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.18 no.3
• /
• pp.273-278
• /
• 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.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.40 no.8
• /
• pp.1107-1112
• /
• 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.

• Advances in Traditional Medicine
• /
• v.9 no.2
• /
• pp.142-148
• /
• 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.

• Korean Journal of Soil Science and Fertilizer
• /
• v.48 no.2
• /
• pp.73-80
• /
• 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.

• Journal of Microbiology and Biotechnology
• /
• v.7 no.2
• /
• pp.144-150
• /
• 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.

• Environmental Engineering Research
• /
• v.19 no.2
• /
• pp.145-149
• /
• 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.

• Journal of Preventive Medicine and Public Health
• /
• v.26 no.2 s.42
• /
• pp.231-250
• /
• 1993

Thirty five male Sprague-Dawley rats were treated with cadmium chloride solution ranging from 0.2 to 3.2mg $CdCl_2/kg$ by intravenous single injection. At 48 hours after administration of cadmium, total cadmium, MT bound cadmium and histopathologic finding in liver, kidney, lung, heart, testis, metallothionein in liver, kidney and total cadmium in bleed were examined. Tissue cadmium concentration was highest in liver, followed by in kidney, heart, lung and testis. Cadmium bound to rnetallothionein (MT-Cd) and ratio of MT-Cd to total cadmium were increased in liver and kidney dependently of cadmium exposure dose, but not significantly changed in other organs. On histopathologic finding, the most susceptible organ was heart in considering cadmium exposed dose, but testis in considering cadmium concentration. Blood cadmium concentration was increased with dose-dependent pattern, and significantly correlated with tissue cadmium concentration, so that we may estimate tissue cadmium concentration by measurement of blood cadmium concentration. Metallothionein in liver and kidney was increased with dose-dependent pattern, higher in liver than in kidney, and was significantly correlated with tissue cadmium concentration. However, metallothionein induction efficiency of tissue cadmium(${\mu}g\;MT/{\mu}g\;Cd$) was eater in liver than in kidney, and reverse to tissue concentration or exposed dose of cadmium.