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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Biomolecules & Therapeutics
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Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 3, Issue 4 - Dec 1995
Volume 3, Issue 3 - Sep 1995
Volume 3, Issue 2 - Jun 1995
Volume 3, Issue 1 - Mar 1995
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Chemoprotective Effect of Methanol Extract of Hedera rhombea Loaves on the Reversal of Cytochrome P-450 Activities Induced by Carbon Tetrachloride
Biomolecules & Therapeutics, volume 3, issue 4, 1995, Pages 245~250
The carbon tetrachloride(
) has been demonstrated to have a hepatotoxic effect in human or many other species. To investigate the enzyme induction of mixed function oxygenases in liver of male Sprague-Dawley rats a single 0.1, 0.5 mι/kg dose of carbon tetrachloride were given. At 24 hr after a single dose of 0.1 mι CC1
/kg weight, methanol extract of Hedera rhombea leaves was administered with 100, 500 mg/kg weight. Assays of 7-ethoxyresorufin-Ο-deethylation(EROD),7-benzyloxyresorufin-Ο-deathylation(BROD),4-nitro-phenol-UDP-glucuronosyltransferase(UDPGT), Western blot and RNA slot blot were used as representatives of the activities of cytochrome P-450 enzymes. The change of the activity of CYP1A1 form measured by EROD assay and Western analysis using 1-7-1 monoclonal antibody was not observed. The activity CYP2B1 form by BROD assay and using 2-66-3 monoclonal antibody was remarkably increased. Elevated level of CYP2B1 mRNA was shown by slot hybridization with 2B1-specific probe. Administration of methanol extract of Hedera rhombea leaves reversed the enzyme activity and the level of mRNA, which suggest the chemoprotective effect of methanol extracts of Hedera rhombea leaves to carbon tetrachloride hepatotoxlcity.
Antigenicity of DA-3002, a Genuine Recombinant Human growth Hormone, in Guinea Pigs and Mice
Biomolecules & Therapeutics, volume 3, issue 4, 1995, Pages 251~255
DA-3002 is a genuine human growth hormone produced by Dong-A Pharm. Co. Ltd. research laboratory using recombinant DNA technic. In this study, antigenic potential of DA-3002 was examined by active systemic anaphyaxis(ASA) in guinea pigs, mouse-rat passive cutaneous anaphylaxis(PCA) and passive hemagglutination(PHA) test as a part of safety research. DA-3002 induced anaphylactic shock in ASA test using guinea pigs Immunized with DA-3002 alone or DA-3002 incoporated into Freund's complete adjutant(FCA) when challenged with 10 times higher dose of anticipated clinical dose of DA-3002. In the mouse-rat PCA and PHA test, DA-3002 also showed positive results. DA-3002, therfore, was considered to produce IgE, IgG, and/or IgM in mice. The results of this study were similar to those of the other human growth hormones and these positive results were thought to be caused due to the fact that both DA-3002 and the other human growth hormones were heterogenous proteins to guinea pigs and mice. Considering the fact that DA-3002 is a genuine human growth hormone of which structure is identical with indigenous human growth hormone, DA-3002 is thought not to cause immunological problems in clinical use.
Capsaicinoids-induced Neurotoxic Desensitization in Guinea Pig: Antinociception and Loss of Substance P-like Immunoreactivity from Peripheral Sensory Nerve Endings in Bronchi
Jung, Yi-Sook ; Lee, Buyean ; Shin, Hwa-Sup ; Kong, Jae-Yang ; Park, No-Sang ; Cho, Tai-Soon ;
Biomolecules & Therapeutics, volume 3, issue 4, 1995, Pages 256~259
Antinociceptive and desensitizing effects of systemically administered capsaicinoids (capsaicin and KR25018) were investigated in guinea pig. Nociceptive sensitivity to chemical stimulus was examined to test sensory function, and the content of substance P-like immunorractivity (SP-LI) in bronchi was determined as a peripheral marker of capsaicin-sensitive primary afferent neurons. Guinea pigs were pretreated s.c. with several doses of capsaicin (1,2.5,5, 10 mg/kg) or KR25018 (1, 2.5, 5, 10 mg/kg) one week prior to the experiments. Frequency of eye wiping was significantly decreased by capsaicin and KR25018 in a pretreatment dosedependent manner. In capsaicin- or KR25018-pretreated guinea pigs, there was a significant loss of SP-LI in bronchial tissue extracts. In summary, a newly synthesized capsaicin analogue H725018 exhibited antinociceptive effect against chemical stimulus in guinea pig, with comparable potency to capsaicin. This desensitizing activity of capsaicin or KR25018 might be related to the loss of SP-LI in peripheral afferent nerves.
Effects of Glycerol on the Oxygen Free Radical Reactions and Renal Functions in the Renal Cortex of Rats
Biomolecules & Therapeutics, volume 3, issue 4, 1995, Pages 260~265
In an attempt to define the early biochemical determinants that participate in the pathogenesis of glycerol-induced nephrotoxicity, especially focusing on oxygen free radicals, we studied malondialdehyde (MDA) level and the activities of catalase and superoxide dismutase in the renal cortex of rats, and the concentrations of blood urea nitrogen(BUH) and serum creatinine of rats at 24hr after the injection of a 50% solution of glycerol. Sprague-Dawley albino rats weighing 240 to 260 mg were injected intramuscularly with a 50% solution of glycerol(2 mι/kg, 4 mι/kg and 8 mι/kg). The group treated with glycerol showed significantlv higher MDA level and catalase activity, lower SOD activity and higher BUN and serum creatinine concentrations at 24 hr after the injection as compared to those of control group. These results suggest that the excessive oxygen free radicals resulting from the depression of SOD activity is an important determinant in the pathogenesis of glycerol-induced nephrotoxicity.
A Monoclonal Anti-peptide Antibody against
2-adrenergic Receptor Which Specifically Binds [
Shin, Chan Young ; Noh, Min Su ; Lee, Sang Derk ; Lee, Sang Bong ; Ko, Kwang Ho ;
Biomolecules & Therapeutics, volume 3, issue 4, 1995, Pages 266~272
The analysis of membrane receptors for hormones and neurotransmitters has progressed considerably by pharmacological and biochemical means and more recently through the use of specific antibodies. To generate and characterize a moloclonal antibody against
-adrenergic receptor, a synthetic
2-adrenergic receptor peptide (Phe-Gly-Asn-Phe-Trp-Cys-Phe-Trp-Thr-Ser-lle-Asp-Val-Leu) which may comprise part of
-adrenergic receptor ligand binding pocket was coupled to Keyhole Limpet Hemocyanin (KLH) and used as an immunogen. Male BALB/C mice were immunized with this antigen and the immunized spleen was fused with myeloma SP2/0-Ag14 cells to produce monoclonal antibodies. Two clones were obtained but one of monoclonal antibodies, mAb5G09, was used throughout in this study because the other clone, mAb5All showed weak immunoreactivity against KLH as well. The mouse monoclonal antibody mAb5G09 produced in this study showed immunoreactivity to peptide-KLH conjugates and also to human A43l cells and guinea pig lung
2-adrenergic receptor as revealed by ELISA and western blot. In the course of determination of the effects of mAb5G09 on
-receptor ligand binding, it was observed that mAb5G09 specifically bound
-adrenergic radioligand [
H]dihydroalprenolol (DHA) with a dissociation constant (Kd) of 60 nM. The [
H]DHA binding activity of mAb5G09 had characteristics of immunoglobulins and the binding activity was not observed in the control anti-KLH monoclonal antibody. The monoclonal antibody, mAb5G09 produced in this study may provide useful models for the study of the structure of receptor binding sites.
The Effect of Methamphetamine on the Pulmonary Metastasis of B16 Melanoma Cells
Biomolecules & Therapeutics, volume 3, issue 4, 1995, Pages 273~278
The effect of methamphetamine on the pulmonary metastasis was investigated in C57BL/6 mice injected with Bl6 melanoma cells. Bl6 melanoma cells (2
cells) were injected intravenously into 5~7 weeks old C57BL/6 mice. Mice were then treated intraperitoneally with methamphetamine either acutely (two times with one week interval) or subchronically (daily for 14 days). Degree of pulmonary metastasis was investigated and specific immunologic parameters such as natural killer cell cytotoxicity(NKCC), antibody-dependent cellular cytotoxicity(ADCC) and blastogenic responses of splenocytes were examined. Mice which had been subchronically treated with methamphetamine showed significant decreases in the number of pulmonary metastasis of Bl6 melanoma cells, NKCC and ADCC without a significant change in blastogenic responses. In the acutely-treated group, slight trends of decrease in the numbers of pulmonary metastasis, NKCC and ADCC were observed without statistical significances whereas there was a significant increase in blastogenic responses. The mechanism underlying the decrease in the degree of metastasis despite diminished NKCC and ADCC after methamphetamine treatment and the relationship between the degree of pulmonary metastasis and duration of methamphetamine treatment remain to be investigated.
Study on the Inhibitory Effects of Diallyl Sulfide and/or Diallyl Disulfide in the Rat Hepntocarcinogenesis
Biomolecules & Therapeutics, volume 3, issue 4, 1995, Pages 279~287
This study examined the anti-cancer effects of diallyl sulfide(DAS) and/or diallyl disulfide(DDS), major components of garlic oil, with the DEN-PH model in rats, by the numbers and areas per cm
of induced glutathion S-transferase placental form(GST-P) positive foci and silver-stained nucleolar organizer regions(Ag-NORs) counts per nuclei in liver as indicator. Sprague-Dawley(SD) rats were given the diethylnitrosamine(DEN, 200 mg/kg, i.p.) as initiator and 2 weeks later, in experiment 1, rats were treated with DAS(200 mg/kg, i.g.) and/or DDS(50 mg/kg, i.g.) for 6 weeks, respectively and concomitantly and also were given the same dose of DAS and/or DDS prior to DEN treatment for 2 weeks, and in experiment II, rats were treated with potential cancer promoter, 2-acetylaminofluorene (2-AAF, 20 mg/kg, i.g.). The DAS and/or DDS were treated prior to 2-AAF for 8 weeks, respectively and concomitantly. Then the anti-promoting effects of DAS and/or DDS were assessed. All rats were subjected to the two-thirds partial hepatectomy(PH) at week 3 and sacrificed at week 8. In experiment I, DAS and/or DDS treatment only prior to DEN showed inhibition of the development of GST-P positive foci. In experiment II, DAS and/or DDS treatment prior to 2-AAF promotion showed obvious inhibition of the development of GST-P positive foci in numbers and areas and AgNORs counts. In conclusion, We found DAS and/or DDS had the preventive effects on the hepatocarcinogenesis in rats and the concomitant treatment had some additive effects compared with the each treatment and AgNORs counts correlated well with the preneoplastic hepatic lesion.
Effect of Lead Intoxication on Thiamine Content and Transketolase Activity in the Brain of Rats
Ryu, Jae-Ryeong ; Cheong, Jae-Hoon ; Kim, Hye-Chung ; Lee, Sang-Derk ; Ko, Kwang-Ho ;
Biomolecules & Therapeutics, volume 3, issue 4, 1995, Pages 288~293
In the present study, we tested whether lead intoxication could change the thiamine content and the activity of transketolase, one of thiamine-dependent enzymes, in the brain of rats. It was also tested whether administration of excessive thiamine can reverse the toxic manifestation of lead in the lead intoxicated rats. Four groups of Wistar rats were prepared: 1) control group, 2) lead treated group, 3) lead plus thiamine treated group and 4) thiamine deficient group. Each group of animals was divided into three subgroups based on ages: 3, 7 and 16 weeks. Lead concentration, thiamine content and the activity of transketolase in three different brain regions, i.e.,, telencephalon, brain stem and cerebellum, were measured in each group. Lead concentrations in brain regions of the lead treated group were significantly higher than those of the control group, and those of the lead plus thiamine treated group were significantly decreased from those of the lead treated group. Thiamine contents in the brain regions of the lead treated group were significantly lower than those of the control group, and those of the lead plus thiamine treated group were recovered back to those of the control group. Activities of transketolase in the brain regions of the lead treated group and the thiamine deficient group were significantly lower than those of the control group, while those of the lead plus thiamine treated group were higher than the lead treated group. The results from the present study suggest that neurotoxicity following lead intoxication in rats may be mediated, at least in part, through the changes of thiamine status and consequently thiamine-dependent biochemical reactions such as theactivity of transketolase.
Mutagenicity Study of DA-3002, an Authentic Recombinant Human Growth Hormone(rhGH)
Biomolecules & Therapeutics, volume 3, issue 4, 1995, Pages 294~300
DA-3002, an authentic recombinant human growth hormone(rhGH), was examined for mutagenicity in the reverse mutation test on bacteria, in the chromosomal aberration test on cultured mammalian cells and in the micronucleous test on mice. The reverse mutation test was performed by a plate incorporation method with or without a metabolic activation system(S9 Mix) using Salmonella typhimurium strain TA100, TA1535, TA98 and TA1537. DA-3002 did not significantly increase revertant colonies in any of the test strains under any conditions at dose levels ranging from 0.0125 to 0.4 IU/plate, compared with the vehicle control. In the chromosomal aberration test using cultured Chinese hamster lung(CHL) cells, DA-3002 did not increase the number of aberrant cells in the presence or absence of S9 mix at concentrations of 0.0125 IU/mι to 0.4 IU/mι, compared with the vehicle control. In the micronucleus test, male ICR mice were given DA-3002 intraperitoneally at a dose level of 20, 40 and 80 lU/kg. The incidence of bone marrow micronucleated polychromatic erythrocytes in the DA-3002 treated mice did not differ from that of the vehicle control. These results indicate that DA-3002 doesn't have mutagenic potential under the present test conditions.
Effects of Crude Ginseng Saponin on the Thromboxane Synthesis in Lipopolysaccharide-stimulated Macrophages
Ryu, Jae-Ha ; Lee, Soo-Hwan ; Moon, Chang-Hyun ; Han, Yong-Nam ; Han, Byung-Hoon ;
Biomolecules & Therapeutics, volume 3, issue 4, 1995, Pages 301~303
Crude ginseng saponin fraction reduced the production of thromboxane
in the lipopolysaccharide-stimulated macrophages. Several kinds of crude saponins showed variant potency that might be caused by the compositional difference of ginseng saponins. From the metabolic labeling experimental data, this reduction of thromboxane
formation, at least in part, resulted from the reduction of protein synthesis of inducible isozyme of cyclooxygenase(COX-2). This activity may be resulted from the fact that ginseng saponins have steroidal moiety in their structures.
Effect of Vitamin C on Hepatic Biliary and Microsomal Function in Hepatic Ischemia/reperfusion
Biomolecules & Therapeutics, volume 3, issue 4, 1995, Pages 304~310
This study was done to investigate the effect of vitamin C on hepatic biliary and microsomal function during ischemia and reperfusion. Rats were treated with vitamin C(20, 100, 400, 1600 mg/kg) or with vehicle(saline) and then subjected to 60 min no-flow hepatic ischemia in vivo. Control animals were time-matched sham ischemic animals. After 1 or 5 hr of reperfusion, bile was collected, blood was obtained from the abdominal aorta, and liver microsomes were isolated. In vehicle-treated ischemic rats, serum ALT and AST levels peaked at 5 hr and were significantly attenuated by vitamin C 20 mg/kg and 100 mg/kg treatment. Similarly, hepatic wet weight-to-dry weight ratio was decreased in the vehicle-treated ischemic group. Vitamin C 20 mg/kg and 100 mg/kg treatment minimized the increase in this ratio. Lipid peroxidation was elevated in vehicle-treated ischemic group, but this elevation was also inhibited by vitamin C 20 mg/kg and 100 mg/kg treatment. Bile flow and cholate output, but not bilirubin output, were markedly decreased by ischemia/reperfuzion. Vitamin C 20 mg/kg and 100mg/kg treatment restored the secretion but vitamin C 1600 mg/kg reduced the cholate output. Cytochrome P-450 content was decreased by ischemia/reperfusion and restored by vitamin C 20 mg/kg and 100 mg/kg treatment to the level of sham operated group but decreased by vitamin C 1600 mg/kg. Aminopyrine N-demethylase activity was decreased and aniline p-hydroxylase activity was increased by ischemia/reperfusion. The changes in the activities of aminopyrine were prevented by vitamin C 20 mg/kg and 100 mg/kg treatment, but not by 400 mg/kg and 1600 mg/kg treatment. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory functions as well as microsomal drug metabolizing systems, small doses(20, 100 mg/kg) of vitamin C significantly ameliorates and large doses(400, 1600 mg/kg) of vitamin C aggravated these ischemia/reperfusion-induced changes.
Purification, Characterization and Cellular Localization of Klebsiella aerogenes UreG Protein
Lee, Mann-Hyung ;
Biomolecules & Therapeutics, volume 3, issue 4, 1995, Pages 311~315
The K. aerogenes ureal gene product was previously shown to facilitate assembly of the crease metallocenter (Lee, M. H., Mulrooney, S. B., Renner, M. J., Markowicz, Y., and Hausinger, R. P. (1992) J. Bacteriol. 174, 4324-4330). UreG protein has now been purified and characterized. Although the protein is predicted to possess a putative NTP-binding P-loop motif, equilibrium dialysis studies showed negative results. Immunogold electron microscopic studies using polyclonal antibodies directed against UreG protein confirm that UreG is located in the cytoplasm as predicted in the DNA sequence.
Safety Evaluation of LB10522, a New Cephalosporin Antibiotic
Kim, Seong-Il ; Raffi Mikaelian ; Kwak, Jin-Hwan ; Kim, In-Chull ; Lee, Chang-Ho ;
Biomolecules & Therapeutics, volume 3, issue 4, 1995, Pages 316~321
All the pharmacological studies of LB17522 described here were carried out with high doses (fifteen to sixty times of the therapeutic dose) to determine an indication of potential side effects in clinical use in terms of the acute clinical signs, cardiovascular and central nervous system. LB10522 does not produce any observable clinical signs except for the symptoms such as moist eye, skin rash, slight salivation, vomitting, and slightly reduced activity. The effects of LB10522 on the hemodynamics and cardiac function of anesthetized beagle dogs are as follows; heart rates and mean arterial blood pressure had a tendency to increase mildly, which is a normal finding in anesthetized dogs. All the animals except for one showed relatively stable respiratory rates throughout the observation period. Each animal treated with LB10522 showed slight increase in the left cardiac work and left ventricular stroke work which are mainly related to corresponding increases in cardiac output. Femoral blood flow were shown to be increased in some animals treated with LB10522. The epileptogenic activities of various cephalosporins were assessed by a direct intracerebral injection of appropriate concentration of test articles. The CD
values (nmol) obtained from the analysis of the dose-response data are as follows; 78.2, 175.3, 156.3, and 53.5 for cefazolin, cephaloridine, ceftazidime, and LB 10522, respectively. LB10522 seems to be equipotent with cefazolin or to be three times more potent than cephaloridine and ceftazidime in causing adverse CNS stimulation. Taken into consideration all the information obtained, LB10522 is not supposed to induce much changes in the functions examined in these studies in man at therapeutic doses.s.
Safety Evaluation of LB20304, a New Quinolone Antibiotic
Kim, Seong-Il ; Kim, Hee-Jin ; Kwak, Jin-Hwan ; Kim, In-Chull ; Lee, Chang-Ho ;
Biomolecules & Therapeutics, volume 3, issue 4, 1995, Pages 322~326
General pharmacology of LB20304, a quinolone antibiotic, were examined in terms of general behaviour, cardiovascular, and central nervous system. LB20304 at oral dose of 2,000 mg/kg did not induce significant behavioural changes in mice. In contrast with ciprofloxacin, LB20304 at dose of 20 mg/kg, iv. did not show any observable effects on the blood pressure in rats. Displacement of [
H]muscimol binding to the rat brain synaptic membranes was measured. LB20304 was shown to be about five times less potent than ciprofloxacin in specific GABA receptor binding. Drug interaction between LB20304 and 4-biphenyl acetic acid, an active metabolite of fenbufen, was assessed in mice by measuring convulsion and/or subsequent death. A single oral pretreatment with 4-BPA at 400 mg/kg increased the incidence of convulsion and death after oral administration of ciprofloxacin at the doses of 25, 50, and 100 from zero of five to three of five, two of five, and four of five, respectively, whereas LB20304 alone or combination with 4-BPA caused neither convulsions nor death at the doses of 12.5, 25, 50, and 100 mg/kg, respectively. Quinolones-induced epileptogenic activities were assessed by a direct intracerebral injection of test articles. The CD
values (nmole) are as follows; 169.47, 35.36, 105.29, and 88.67 for LB20304, ciprofloxacin, of loxacin, and lomefloxacin, respectively. From these data, LB 20304 at therapeutic doses seems to be much more safe than any other quinolones tested.d.