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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Biomolecules and Therapeutics
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Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 2, Issue 4 - Dec 1994
Volume 2, Issue 3 - Nov 1994
Volume 2, Issue 2 - Aug 1994
Volume 2, Issue 1 - Apr 1994
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Protective Effect of Brazilin on Cisplatin Nephrotoxicity
Kong, Jae-Myeong ; Seo, Kyung-Won ; Choung, Se-Young ;
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 103~107
Cisplatin is one of the most effective antitumor agents currently available for cancer therapy. However, its clinical use has been limited by its severe side effects, especially nephrotoxicity. Therefore, brazilin, which has a radical scavenging effect, was given intraperitoneally to evaluate the effect on cisplatin nephrotoxicity in rats. Remarkable protective effects against nephrotoxicity of cisplatin were observed when brazilin was administered to rats simultaneously with cisplatin. Hepatotoxicity induced by combination treatment of cisplatin and brazilin was evaluated by measuring serum glutamic pyruvate transaminase and serum glutamic oxalate transaminase. Combination treatment did not affect the levels of sGPT and SGOT, and any combination treatment did not induce metallothionein in kidney. Brazilin which has radical scavenging effect directly reduced nephrotoxicity of wisplatin in vivo. Thus, it seems that nephrotoxicity of cisplatin was caused by free radicals. The present results Indicate that brazilin, when it is given with cisplatin, may provide protection against cisplatin nephrotoxicity in rats.
Studies on Hypersensitivity of Recombinant Hepatitis B Vaccine (LBD-008) in Mice and Guinea pigs
Park, Jong-Il ; Ha, Chang-Su ; Han, Sang-Seop ;
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 108~113
Toxicity study of recombinant hepatitis B vaccine (LBD-008), a newly developed drug for acute and chronic hepatitis, was investigated in mice and guinea pigs. 1. Mice showed no production of antibodies against LBD-008 inoculated with aluminum hydroxide gel (Alum) as an adjuvant, judged by the heterologous anaphylaxis (PCA) test using rats. On the other hand, antibodies against ovalbumin (OVA) inoculated with alum were definitely detected. 2. In the studies with guinea pigs, both the inoculation of LBD-008 only and of LBD-008 with complete Freund's adjuvant (CFA) as an adjuvant did not produce positive reactions in any of homologous active systemic anaphylaxis (ASA). On the other hand, the inoculation of ovalbumin with complete Freund's adjuvant (CFA) produced positive reaction in both of PCA and ASA. 3. These findings suggested that LBD-008 has no antigenic potential in mice or guinea pigs.
Studies on Digitalis Receptor Desensitization in Rat Ventricle
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 114~119
H]Ouabain binding parameters (
) to control rat ventricular strips and Langendorff preparations which were not previously exposed to ouabain were compared with those to both preparations that had been first exposed to a complete ouabain dose range of dose-response curve (10
M). In rat ventricular strips and Langendorff perfused heart preparations, cumulative dose-response curves of ouabain revealed biphasic positive inotropic effects, a "low-dose" effect and a "high-dose" effect with E
values of 0.5
M and 35
M ouabain, respectively. The "low-dose" effect in ventricular strip disappeared or was diminished significantly when the ouabain dose-response curve was repeated after the washout of the effects of the first dose-response curve, whereas there were no significant differences in the maximal "high-dose"effect in both exposures to oubain. However, both of the control and ouabain-preexposed Langendorff perfused hearts revealed the same low-dose effects. The
value for [
H] ouabain binding and the ouabain binding site concentration (
) estimated by [
H]ouabain displacement assay in control preparations were 230 nM and 2 pmol/mg protein, respectively. [
H]Ouabain binding parameters were not changed by repeated exposure to high concentrations of ouabain. These results suggest that digitalis receptor desensitization in the rat ventricular strip may due to the change of post-receptor events induced by ouabain binding to a high affinity site (
Determination of Remained Host Derived Proteins in the Commercially Available Biotechnological Products Using a Sandwich Enzyme Linked Immunosorbent Assay Method
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 120~125
We obtained the total protein antibodies of Saccharomyces cerevisiae KCTC 1720 and Escherichia coli K-12 from the rabbit and the guinea pig to determine the host-derived proteins which may be remained in biotechnological products. The protein concentration of rabbit antibodies was 4.05 mg/mι in the case of yeast, 7.14 mg/mι in the case of E. coli and that of guinea pig antibodies was 1.90 mg/mι in the case of yeast, 7.17 mg/mι in the case of E. coli, respectively. To determine remained host-derived proteins in biotechnological products which produced by the hosts, S. cerevisiae or E. coli, we used a sandwich enzyme linked immunosorbent assay method in 96 well microplate. When the method applied to determine the remained host-derived proteins in commercial biotechnological products, it detected less than 3.5 ng/vial in human growth hormone, less than 1 ng/vial in hepatitis B vaccine and interferon-
and 2~23 ng/vial in interferon-
. The method can be used to determine the remained host-derived protein in biotechnological products.
Immunopotentiating and Antitumor Activities of Purified pectins and Polysaccharides from Trichosnnthes Rhizoma and Taraxii Herba
Park, Soo-Wan ; Chung, Yeoun-Bong ; Kim, Hye-Kyung ; Lee, Chung-Kyu ;
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 126~130
Water-soluble pectins isolated from Trichosanthes Rhizoma and Taraxii Herba and their deproteinized polysaccharides were purified through DEAE cellulose column and were applied to immunopotentiating and antitumor studies to clarify the nature of their activities of our previous reports. As the results of works, the lectins and deproteinized polysaccharides increased the number of circulating leukocytes and total peritoneal cells. And they markedly elevated the lowered production of antibody and reactivity of T Iymphocyte in tumor-bearing mice, which were rapidly recovered by discontinuance of sample treatments. They also decreased the growth of Sarcoma 180 solid tumor in mice.
Effect of Ginsenoside on Basal and Nitro-L-Arginine Suppressed Nitric Oxide Production in Rat Kidney
Kim, Hye-Young ; Han, Sang-Won ;
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 131~135
The effect of ginsenoside (GS) from Panax ginseng on basal and nitro-L-arginine suppressed nitric oxide (NO) production was studied in rat kidney. NO production was determined by conversion to [
]=L-citrulline from [
]-L-arginine both in whole kidney and three renal segments; glomerulus, cortex excluding glomerulus (cortex-) and medulla. Nitro-L-arginine (total dose of 30 mg/kg/3 days, i.p.) significantly reduced NO production in whole kidney, which was prevented by GS pretreatment (30 mg/kg/3 days, i.p.). Relative high dose of GS (120 mg/kg/4 days, i.p..) selectively increased NO production in glomerulus and cortex-. Protein content, on wet weight basis, in cortex- and glomerular DNA content were significantly reduced by GS. Our results confirm the existence of constitutive nitric oxide synthase in kidney and it seems that target nephron segment for volume expansion due to GS'NO-mediated vasodilation and for NO production stimulated by GS is cortex including glomerulus.lus.
Another Evidence for Nitric Oxide as Mediator of Relaxation of Isolated Rabbit and Human Corpus Cavernosum
Chang, Ki-Churl ;
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 136~140
To prove the hypothesis that NO- and N
-carrying molecules potentiate photorelaxation by generating NO, investigation was carried out using isolated rabbit and human corpus cavernosum. Corporal smooth muscle, in the presence or absence of endothelium, relaxed only slightly upon ultraviolet light (366 nm) irradiation. But, NO-and/or N
-containing compounds such as streptozotocin and
-nitro-L-arginine methyl ester significantly (p<0.01) enhanced photorelaxation in this tissue. In addition,
-nitro-D-arginine methyl ester, known to lack inhibitory action on NO synthase, showed concentration-dependent potentiation of the photorelaxation. Oxygen radical generating system via copper＋ascorbic acid and guanylate cyclase inhibitor, methylene blue, significantly (p<0.05) inhibited the streptozotocin-potentiated photorelaxation. Nitrite was accumulated by photolysis of streptozotocin,
-nitro-L-arginine methyl ester and
-nitro-D-arginine methyl ester, in a concentration and exposure time dependent manner. These observations indicate that NO is a potent relaxant of rabbit and human corpus cavernosum and further support the hypothesis that NO is released by photolysis from NO- and N
Lipid Peroxidation of Hepatic Microsomal Drug-Metabolizing System in Hepatic Ischemia ands Reperfusion
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 141~148
This study was done to determine whether specific alterations exist in hepatic microsomal function after varying periods of ischemia (IS) and reperfusion (RP) during microsomal lipid peroxidation occurs. Rats were pretreated with
-tocopherol to inhibit lipid peroxidation or with vehicle (soybean oil). Control animals were time-matched sham-ischemic animals. Four groups of animals were studied: Group 1 (sham), group 2 (30 mins IS), group 3 (60 mins IS) and group 4 (90 mins IS). After 1, 5 or 24 hr of reperfusion, liver microsomes were isolated and cytochrome P-450s were studied. In all vehicle-treated ischemic rats, serum ALT levels peaked at 5 hr and were significantly reduced by
-tocopherol pretreatment. Similarly, microsomal lipid peroxidation was elevated in all vehicle-treated ischemic animal groups, but this elevation was prevented by
-tocopherol pretreatment. Cytochrome P-450 content was significantly decreased in both group 3 and group 4. In all vehicle-treated ischemic animal groups, aminopyrine N-demethylase activity was significantly decreased for the entire reperfusion period.
-Tocopherol inhibited reductions of cytochrome P-450 content and aminopyrine N-demethylase activity at both 1 hr and 5hr of reperfusion but did not affect the reduced levels of cytochrome P-450 content and aminopyrine N-demethylase activity at 24 hr of reperfusion. Aniline p-hydroxylase activity was significantly decreased in group 4, whereas it was increased in group 3. These decreases and increases were prevented by
-tocopherol pretreatment. Our finding suggests that abnormalities in microsomal drug metabolizing function occur during hepatic ischemia and reperfusion in vivo and this is attributed to microsomal lipid peroxidation.
Anti-allergic and Anti-inflammatory Actions of Cimicifuga heracleifolia: Partial Purification of Active Components
Kim, Young-Ran ; Park, Soo-Hyung ; Kim, Kyeong-Man ;
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 149~154
Anti-allergic and anti-inflammatory actions of the water extract from Cimicifuga heracleifolia were evaluated in mice and rats. Several criteria were employed to assess the anti-allergic and anti-inflammatory actions of Cimicifuga heracleifolia, such as hyaluronidase activity, mediators-induced vascular permeability changes, 48 hour homologous passive cutaneous anaphylaxis (PCA) histamine release from mast cells, and the carrageenan-induced rat paw edema. To further characterize the active components, the water extract was either extracted with organic solvent or fractionated according to molecular weight, and each fraction was tested for some of anti-allergic parameters. Hyaluronidase activities, both in activating and in activated states, were significantly inhibited by the water extract of Cimicifuga heracleifolia and by some of its subfractions, molecular weight less than 1,000. The water extracts (50~400 mg/kg) significantly inhibited 48 hr homologous PCA and vascular permeability changes induced by chemical mediators (histamine, serotonin, and leukotriene
) in mice. In the case of histamine-induced vascular permeability changes, more extensive studies were conducted; water extract was either fractionated according to molecular weight or extracted with butanol. Anti-histamine actions were observed only from the water layer, and these active components were of the molecular weight less than 1,000. These anti-allergic actions were observed mainly from mice than from rats. On the other hand, anti-inflammatory actions of the water extract from Cimicifuga heracleifolia were significant in rats.
Inhibition of HIV-1 Pretense by Novel Dipeptide Isosteres Containing 2-Isoxazoline or
Kim, Do-Hyung ; Park, Kwan-Yong ; Chung, Yong-Jun ; Kim, Byeang-Hyean ;
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 155~160
Human immunodeficiency virus type 1 (HIV-1) protease is essential for the replication of the virus and it is therefore an attractive target for antiviral drugs of HIV-1. Several dipeptide isosteres containing 2-isoxazoline or
-hydroxy ketomethylene have been synthesized and their inhibitory effects on the HIV-1 protease examined. The enzymatically active HIV-1 protease was purified to homogeniety from E. coli transformed with a recombinant plasmid (pMAL-pro) containing the entire gene encoding the protease. The purified protease had the substrate specificity with Km value of 9.8
M when an undecapeptide His-Lys-Ala-Arg-Val-Leu-(p-nitro)Phe-Glu-Ala-Nle-Ser-amide was used as a substrate, and the products from the substrate after specific cleavage by HIV-1 protease were analyzed by HPLC. The synthetic compounds containing dipeptide isosteres showed specific inhibitory effects while a dipeptide isostere containing an isoxazoline ring inhibited the HIV-1 protease competitively with Ki value of 500
M. Even if the inhibition effects of HIV-1 protease were not very high, these novel dipeptide isosteres can be used as key structural moieties for developing specific inhibitors of HIV-1 protease.
Single and 13-week Repeated Dose Toxicity Study of DA-3002, An Authentic Recombinant Human Growth Hormone
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 161~172
This study was conducted to examine DA-3002, a biosynthetic human growth hormone, for its acute and subacute toxicities in mice and rats. The drug was administered subcutaneously and orally at a dose level of 1.0, 3.0, 8.9, 26.7 or 80.0 lU/kg once for single dose toxicity and given subcutaneously at a dose level of 0.34, 1.7 or 8.4 lU/kg daily for 13 weeks to investigate repeated dose toxicity. In the acute toxicity study, doses up to 80 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal changes which could be attributed to toxic effect of DA-3002. In the subacute toxicity study, the growth hormone was tolerated well in broth mice and rats. No drug related deaths occurred and all animals appeared to be normal throughout the dosing period. Increases in body weight gain, food utilisation and absolute organ weights were observed in the rats in the high dose group. Mild changes in the blood chemical parameters were also seen in the treated groups. Histopathologically, however, no abnormal changes were observed in any organ. The changes noted during the treatment periods presumably represent exaggerated pharmacological effects of the growth hormone, and no observed adverse effect level (NOAEL) was considered to be more than 8.4 lu/kg/day.
General Pharmacology of DWP 305, a New Combined Drug for Hepatic Diseases
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 173~184
The general and some pharmacological actions of DWP 305 were investigated in animals and the following results were obtained. In central nervous system, DWP 305 had no effects on the pentobarbital induced anaesthesia, locomotor activity, rotarod test, traction test, analgesic action in mice and body temperature in rat. DWP 305 showed no depressive action on convulsion induced by strychnine, electronic shock and pentylenetetrazole. From these results, DWP 305 was considered to have no pharmacological effect on the central nervous system. Furthermore, DWP 305 had no influences on the normal blood pressure and heart rate. In the isolated ileum of guinea pig, DWP 305 inhibited contractive effects against the acetylcholine (10
g/mι), histamine (10
g/mι), 5-hydroxytryptamine (10
g/mι) and BaCl
g/mι) at a concentration of 2.15
g/ml in bath. In the isolated trachea and vats deference, DWP 305 showed no effect on the contractions produced by histamine and norepinephrine, respectively. DWP 305 showed inhibitory effect on the contractions produced by acetylcholine and oxytocin at a concentration of 2.15
g/ml on the isolated nonpregnant rat uterus. DWP 305 had no effect on the isolated right atrium of guinea pig, bile excretion, urine volume, pH, gastrointestinal motility, gastric secretion and blood aggregation.
Therapeutic Effects on Gastrointestinal Diseases of a New Combined Ranitidine Preparations, DWP302
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 185~189
The eight combined products composed of ranitidine.HCI, tripotassium dicitrato bismuthate and sucralfate were prepared with various ratios and studied in therapeutic effects of them on various gastrointestinal diseases. These were induced in rats with the porous ligation, ethanol-HCI, acetic acid and cysteamine method, etc. In all experimental setting, the effect of the combined treating was more pronounced than the effect of each drug alone. Specially, the combined treatment consisted of ranitidine : tripotassium dicitrato bismuthate sucralfate ratio of 1.5 : 2 : 6 showed the most powerful therapeutic effect on acute gastric ulcer model and revealed a significant acceleration of the healing on chronic gastroduodenal ulcer model. And that, therapeutic doses of ranitidine, tripotassium dicitrato bismuthate arid sucralfate given in combination had an additive or, in some case, synergistic effect. From the above results, this combined treatment may useful to heal the gastrointestinal diseases that aren't cured well by treatment of each them alone.
Four-Week Dose-Range Finding and 13-Week Repeated Dose Intravenous Toxicity Studies in Rats with DA-125, a New Anthracycline Antitumor Antibiotic
;;;;;;Eric J. F. Spicer;Susan Novitsky;Lee Bernal;
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 190~205
This study was conducted to investigate the repeated dose toxicity of DA-125, a new anthracycline antitumor antibiotic, in rats. Before the 13-week main study, a 4-week dose-range finding (DRF) study was carried out. The administration of DA-125 intravenously at dosage levels of 0, 0.125, 0.5, 2.0, and 8.0 mg/kg/day to rats for 4 weeks resulted in premature deaths of all animals in the 8.0 mg/kg/day group and in the deaths of 4 males and 4 females at 2.0 mg/kg/day. Body weights were markedly reduced in the 8.0 mg/kg/day group and showed dose-related decreases in all treatment groups when compared with the control group. Reductions in weight gain were slight and not significantly different at 0.125 mg/kg/day but animals receiving 0.5 mg/kg/day showed more marked decreases in gain in a clear dose-related manner Based On the results of the above DRF study, a 13-week repeated dose intravenous toxicity study in rats with DA-125 was performed at a dose level of 0, 0.012, 0.08 and 0.3 mg/kg/day. No treatment related effects were noted in behavior or body weight in all treatment groups. One male at the highest dose level died on study day 26, but the death could not be related to test article toxicity. Swelling and scabbing of the ears was present in all of the groups, including the control group. There were no treatment related changes in the hematological, biochemical or urinalysis values in all treatment groups. Thymus weights were significantly reduced ill males receiving 0.3 mg/kg/day and they were sligltly, and not significantly, reduced in females of the same group. While there were no associated histological changes. Treatment related necrosis was found in the tail vein (injection site) at 0.08 and 0.3 mg/kg/day. On the basis of these results, the no observed effect level (NOEL) was 0.012 mg/kg/day and the maximum tolerated dose (MTD) was estimated to be more than 0.3 mg/kg/day under the conditions tested.
Effects of G009 on Chemical-Induced Liver Damage in Rats
Biomolecules and Therapeutics, volume 2, issue 2, 1994, Pages 206~212
The present study was performed to determine the protective effect of G009 on liver damage induced bv ethanol
and thioacetamide in rats. In acute fatty liver animal model induced by ethanol, triglyceride accumulation was markedly decreased to the normal control level by 25 mg/kg G009 treatment. In addition, G009 significantly reduced serum ALT and AST levels in
-induced acute hepatitis animals. Treatment of G009 to the acute hepatitis rats induced by thioacetamide resulted in a dose dependent reduction of serum ALT level as well as AST level up to the normal control level. These protective effects of G009 were confirmed by histological examinations of the liver. These results suggested that G009 could be effective for the protection from the liver damage induced by ethanol,