Go to the main menu
Skip to content
Go to bottom
REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
> Journal Vol & Issue
Biomolecules & Therapeutics
Journal Basic Information
Journal DOI :
The Korean Society of Applied Pharmacology
Editor in Chief :
Volume & Issues
Volume 6, Issue 4 - Dec 1998
Volume 6, Issue 3 - Sep 1998
Volume 6, Issue 2 - Jun 1998
Volume 6, Issue 1 - Mar 1998
Selecting the target year
Pathophysiologic Characteristics of Airway Mucus-hypersecretory Diseases and Experimental Models
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 1~8
Effects of Hyperbaric Oxygen Treatment on the Malondialdehyde Level and Oxygen Free Radical Reactions in the Heart of the Rats Exposed to Carbon Monoxide
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 9~13
ln an attempt to define the effects of hyperbaric oxygen treatment on the lipid peroxidation and oxygen See radical reactions in rats exposed to carbon monoxide, we studied malondialdehyde(MDA) level and activities of catalase and superoxide dismutase in the heart of the rats exposed to carbon monoxide. Male Sprague-Dawley albino rats weighing 240 to 260gm were used. Experimental groups consist of Control group (=breathing with air), HBO group(=exposed to hyperbaric oxygen(HBO, 3ATA, 100%) after air breath), CO group(=exposed to CO(3,970 ppm) after air breath), CO-Air group(=exposed to CO after air breath followed by air breath) and CO-HBO group(=exposed to CO after ai. breath followed HBO treatment). The CO group showed significantly higher MDA level, catalase activity and SOD activity as compared to that of control group. The CO-HBO group showed significantly lower MDA level as compared to that of CO group, and did not show significantly lower catalase activity and SOD activity as compared to that of CO group. These results suggest that the excessive oxygen free radicals is an important determinant in pathogenesis of Co-induced cardiotoxicity and HBO inhibits the lipid peroxidation caused by excessive oxygen free radicals in the heart of the rats exposed to carbon monoxide.
Non-cytoxic Effects of Cationic Polyamines on Cultured Hamster Tracheal Surface Epithelial (HTSE) Cells
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 14~19
In the present study, we intended to investigate whether cationic polyamines including poly-L-Iysine (PLL) and poly-L-arginine (PLA) induce cytotoxicities to cultured hamster tracheal surface epithelial (HTSE) cells. Confluent HTSE cells were chased for 30 min in the presence of PLL or PLA of different molecular weights. Possible cytotoxicities of PLL or PLA were assessed by measuring both Lactate Dehy- drogenase (LDH) release during treatment and the number of floating cells after treatment and by checking the possible changes on the morphology of HTSE cells during treatment. The results were as follows: in the case of treatment of PLL or rLA of which molecular weight is about 78,000 and 92,000, respectively, (1) there was significant release of LDH during treatment, (2) the number of floating cells were significantly increased after treatment and (3) there were significant changes on the morphology of cultured HTSE cells. However, in the case of PLL or PLA of which molecular weight is under 10,000 (about 9,600 and 8,900, respectively), no significant signs of cytotoxicities mentioned above were detected. We found that cationic polyamines might be non-toxic under specific range of molecular weights and suggest that the cytotoxicity of cationic polyamine might depend on the molecular sizes of each cationic polyamine.
Thiamine Eflects on Electroshock Seizure Threshold of Lead-exposed Rats
Cheong, Jae-Hoon ; Kim, Yun-Tae ; Ryu, Jae-Ryun ; Park, Kyu-Hwan ; Ko, Kwang-Ho ;
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 20~24
In the present study, we tested whether lead intoxication induces change of the thiamine content and the seizure threshold in rats and the changes of seizure threshold are related to the changes of thiamine status. It was also tested whether administration of excessive thiamine could reverse the toxic manifestation of lead in rats. Four groups of Wistar rats were prepared: 1) control group, 2) lead treated group, 3) lead plusthiamine treated group, and 4) thiamine deficient group. Each group of animals was divided into three subgroups based on age: 3, 7 and 16 weeks. In each group, thresholds of electroshock seizure and thiamine contents in brain regions including telencephalon, brain stem, cerebellum were measured. Thiamine contents in brain regions of the lead treated group were significantly lower than those of the control group and thiamine treatment reversed the decrease back to the control level. Thresholds of the electroshock seizure of the lead treated group in 3, 7 week old rats and those of thiamine deficient group in 3 week old rats were significantly lower than those of the control group. These observations were reversed by the supplementation with thiamine. These results from the present study suggest that increased seizure sensitivity induced by lead intoxication in rats may be mediated at least in part through the changes of thiamine status.
Changes of the Extracellular Concentrations of Striatal Dopamine and Its Metabolites by MK-801 in Morphine-Dependent Rats
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 25~30
The roles of dopamine(DA) and N-methyl-D-aspartate(NMDA) system in the development and expression of morphine dependence were investigated by monitoring the concentrations of extracellular DA and its metabolites by in vivo microdialysis and simultaneous observation of behavioral changes in morphine dependent rats. Extracellular DA level in caudate putamen of morphine-dependent rat was decreased and the concentrations of its metabolites, dihydroxy phenylacetic acid(DOPAC) and homovanillic acid(HVA), were increased during naloxone-precipitated withdrawal. DA contents were recovered to normal levels by pretreatment of MK-801, a noncompetitive NMDA receptor antagonist, which may explain the mechanism of diminishing effect of MK-801 on withdrawal symptoms in morphine-dependent rats. MK-801(0.3 mg/tg, i.p.) induced the untoward hamful neurological signs such as ataxia and severe rotations, which may be produced by hyperactivation of dopaminergic system. These results suggest that MK-801 may inhibit the expression of mophine dependence by altering the dopamine release.
Pneumococcal Capsular Polysaccharides Induce the Production of TNF-
and Nitric Oxide in Murine Peritoneal Macrophages
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 31~36
Capsular polysaccharides (CPs) from Streeptococcus pneumoniae were examined for the ability to induce secretory responses in a pure population of peritoneal macrophages. The highly purified CPs were able to affect the macrophage, ie, secretion of tumor necrosis factor-alpha (TNF-
) and nitrite. As after stimulation with CPs, secretion of TNF-u induced by these CPs reached its maximum within the first few hours of the interaction, while secretion of nitrite was increased with time. In addition, production of TNF-
and nitrite was increased in a dose-dependent manner. In the presence of indomethacin, CP-stimulated TNF-
production was not altered. In contrast, LPS with indomethacin stimulated 24.5% more TNF-
than LPS alone, suggesting that the intracellular signaling processes for TNF production are differentially stimulated by CP and LPS. The results demonstrate that CPs are potent inducer of macrophage secretory activities.
Protective Effect of DA-9601, an Artemisiae Herba Extract, on Radiation-induced Colitis in Wistar Rats
Ahn, Byoung-Ok ; Oh, Tae-Young ; Ryu, Byoung-Kweon ; Kim, Soon-Hoe ; Kim, Won-Bae ; Kang, Seung-Hee ; Chun, Mi-Son ; Yoon, Jung-Hee ;
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 37~44
This study was performed to examine the effects of DA-9601, a novel antiulcer agent extracted from Artemisiae Herba, on radiation colitis in the rat. Female Wistar rats received a 30 Gy dose of irradiation to the 2 cm of distal colon in length using an intrarectal applicator system. 30 mg/tg or 100 mg/kg of DA- 9601 was administered orally 30 min before and 4 h after radiation on day 1. And the same dose of DA-9601 was given to the animals twice a day from day 2 to 14. As a reference control, sucralfate suspension (100 or 300 mg/head) was given as an enema based on the same treatment schedule of DA-9601. Body weight change and the frequency of diarrhea were recorded during the observation period as markers of radiationinduced injury, All animals were sacrificed on day 15 for evaluation of macro- and microscopic findings and mucosal myeloperoxidase (MPO) activity. Radiated animals showed diarrhea, mucosal redness and histologic changes characterized by edema and eosinophilic infiltration of the periglandular lamina propria with loss of colonic epithelium. Radiation also significantly increased mucosal MfO activity of affected colon f\\\\\\\\`<0.05). However, most of these changes were completely protected by oral administration with DA-9601. DA-9601 reduced radiation-induced histologic alteration significantly in a dose-related manner (P<0.05). In addition, mucosal MPO activity in rats receiving high dose of DA-9601 decreased significantly when compared with that in radiated control. High dose of sucralfate (300 mg/head) alleviated radiation-induced histologic lesion, but failed to reach statistical significance. The results of this study suggest that DA-9601 can be useful for the prevention of acute clinical symptoms of radiation proctocolitis and that decrease of mucosal MPO by DA-9601 plays a role in its protective mechanism(s), at least in part.
Pharmacokinetic Properties and Antiinflammatory Activity of Ketoprofen Lotion
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 45~49
The pharmacokinetic properties and antiinflammatory activity of 3% ketoprofen lotion (ID-lotion), formulated with poloxamer 407, were evaluated using rats. For the pharmacokinetic study, the lotion, at the dose of 4.5 mg/kg, was applied on the dorsal skin of rats and the drug concentration in plasma was determined using an HPLC method. As references, ketoprofen suspended in saline was administered orally, and E-lotion, which is a 3% ketoprofen lotion in the Japanese market was applied transdermally. Following the transdermal application of ID-lotion and E-lotion,
22.3 ng/ml and 163
12.2 ng/ml, respectively, at the same Tma of 2 hours postdose, while
after oral administration of the drug were 1,030
89.1 ng/ml and 0.25 hours, respectively. Relative bioavailabilities of ID-lotion and I-lotion were 69.3% and 34.2%, respectively. The antiinflammatory activity of the two 3% ketoprofen lotions was evaluated with carrageeneninduced edema method after 50 mg of the lotions was applied on the paw of rats. ID-lotion showed 67.6% inhibition of the edema formation, while I-lotion showed 34.\\\\`r%. The calculated ED5o after transdermal application of ID-lotion was 2.5 mg/kg, while that after oral administration was 7.0 mg/kg. Based on these results, the relative equiponderal availability of ID-lotion was 296% compared to the oral administration of ketoprofen.n.n.n.
Antigenicity Study of Recombinant Human Erythropoietin
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 50~55
Antigenic potential of a recombinant human erythropoietin (rhEPO) produced by Dong-A charm. Co. Ltd. was examined by active systemic anaphylaxis (ASA) test in guinea pigs, mouse-rat passive cutaneous anaphylaxis (PCA) reaction and passive hemagglutination (PHA) test. In ASA test, rhEPO induced the signs of restlessness, rubbing or licking nose, sneezing and coughing in the animals immunized with rhEPO 1000 lU/kg alone or rhEPO 1000 lU/kg incorporated into Freund\\\\`s complete adjuvant. In the mouse-rat PCA test, only one of six sera from the animals immunized with rhEPO 1000 lUng incorporated into Alum showed positive result. In the PHA test, rhEPO revealed negative results in all of the rhEPO-immunized groups. From these results, rhEPO was considered to produce IgE in guinea pigs and mice, but not IgG and/or IsM in mice. The results of this study were similar to those of the other recombinant human erythropoietin and these positive results were thought to be caused due to the fact that rhEPO were heterogeneous proteins to guinea pigs and mice. Considering the fact that rhErO has an identical structure with indigenous human erythropoietin, rhEPO is not thought to cause immunological problems in clinical use.
Mutagenicity Study of Recombinant Human Erythropoietin(rhEPO)
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 56~62
Mutagenicity of recombinant human erythropoietin (rhEPO) was examined in the reverse mutation test on bacteria, in the chromosomal aberration test on cultured mammalian cells and in the micronucleus test on mice. The reverse mutation test was performed by a plate incorporation method with or wothout a metabolic activation system (59 Mix) using Salmonella typhimurium strain TA100, TA1535, TA98 and TA 1537. The rhEPO did not significantly increase revertant colonies in any of the test strains under any conditions at dose levels ranging from 1000 H/ml to 62.5 lu/plate, compared with the vehicle control. In the chromosomal aberration test using cultured Chinese Hamster Lung (CHL) cells, the number of aberrant cells was not increased in the presence or absence of 59 Mix at concentrations of 1000 lU/ml to 250 lU/ml, compared with the vehicle control. In the micronucleus test, male ICR mice were given rhEPO intraperitoneally at a dose level of 25000, 12500 and 6250 lU/kg. The incidence of bone marrow micronucleated polychromatic erythrocytes was not different from that of the vehicle control. From these results, rhEPO is considered to be non-mutagenic under the present test conditions.
Mutagenicity Studies of Five 4-Quinolone Antibiotics in Salmonella, Drosophila and Cultred Chinese Hamster Lung (CHL) Cells
Han, Soon-Young ; Oh, Hye-Young ; Heo, Ok-Soon ; Sohn, Soo-Jung ; Ha, Kwang-Won ;
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 63~72
-4-Quinolone antibiotics (pefloxacin, ciprofloxacin, norfoxacin, ofloxacin and enoxacin) were tested for mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538 and TA102, for chromosomal aberrations in cultured Chinese hamster lung (CHL) cells, and for wing somatic mutations and recombinations (wing spot) in Drosophila. Five 4-quinolones did not show any mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537 and TA1538. However, they were mutagenic inSalmonella typhimurium TA102 with and without metabolic activation in both plate incorporation method and preincubation method. Ciprofloxacin induced structural chromosome aberrations in CHL cells both with and without metabolic activation, and the frequencies were 6% and up to 28%, respectively. Pefloxacin showed equivocal evidence, however, norfloxacin, ofloxacin and enoxacin did not induce the structural chromosome aberrations both in the presence and absence of metabolic activation. In the wing spot assay in Drosophila, ofloxacin increased the frequency of small single spots significantly in a dose-dependent manner but there was no dose-dependent increase of single or twin spots in the others.
Peri- and Postnatal Study of Q-35, a Quinolone Antibiotic, in Rats
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 73~81
Pregnant Sprague-Dawley rats were administered with Q-35 at the dose levels of 0, 30, 100 and 300 mg/kg/day by oral gavage from gestation day 17 to lactation period. Effects of the test chemical on general findings, reproductive performance of dams and development of Fl generation were examined. There were no treatment related changes in physical signs, body weight, necropsy findings, organ weights, delivery and nursing behavior. In 100 and 300 mg/fg/day treated groups, the food consumption of dams was decreased significantly during gestational day 19~21. The gestation length of 300 mg/tg/day treated group was increased significantly compared to the control group (22.3
0.48 vs 22.0
0.39). Although the gestational length of all groups were in normal range of the rat, potential effect of the drug could not be ruled out. External anomaly of Fl fetus induced by Q-35 was not detected in any groups. There were no treaoent related changes in physical development, reflex functions, sensory functions, locomotor activity and motor coordinating activity. Estrus cycle, fertility and reproductive performance of Fl were not changed in all treated groups. There was no external abnormality related to the drug administration on the examination of F2. These results suggest that Q-35 has no adverse effect on the peri- and postnatal period in rats except the reduction of food consumption at the beginning of drug administration and the potential effect on the elongation of gestation length.
Reproductive Toxicity Study of LBO0014, A New Recombinant Human Erythropoietin: Teratogenicity Study in Rats
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 82~88
LBO0014, a new recombinant human erythropoietin, was at dose levels of 0, 120, 600, and 3,000 IU/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. All dams were subjected to caesarean section on day 20 of pregnancy, Effects of test substance on dams and embryonic development of Fl fetuses were examined. No treatment-related changes in clinical signs, body weight, and food consumption were observed at all doses tested. At necropsy spleen enlargement was found at 3,000 lU/kg. There was an ulcrease in the spleen weight at 600 and 3,0007/kg. Developmental toxicity was evident as increased resorptions at 3,000 lU/kg. At 600 and 3,000 RJ/kg, retarded ossification of fetuses occurred at an incidence of 31.3% and 64.7%, respectively. In addition, there was a delay in ossification of sternebrae and sacrocaudal vertebrae at 600 and 3,000 lU/kg. A decrease in the number of metacarpi and metatarsi was also seen at 3,000 nJ/kg. The results show that the no observed adverse effect dose level (NOAEL) for material toxicity was over 3,000 IU/kg/day and the NOAEL for developmental toxicity was 120 IU/kg/day.
Biological Activity and Acute Toxicity of the Multimers of CJ500011 Recombinant Human Granulocyte Colony-stimulating Factor (rHuG-CSF), Produced in E. coli
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 89~94
CJ50001 is a recombinant human granulocyte colony-stimulating facto, (rHuG-CSF) that stimulates the formation of neutrophils from bone marrow stem cells. It was produced in E. colt and purified through refolding and several processes. We produced CS970125(300) using purified C150001 and additives in order to test the stability of CJ50001. When CS970125(300) was stored at 50'S for more than 1 week, high molecular weight proteins were formed and those proteins were detected by non-reducing SDS-PAGE, gel filtration HPLC, and Western blot. Those proteins showed single band at the same position of CJ50001 in reducing SDS-PAGE. These data indicated that those high molecular weight proteins were the multimers of C150001. In biological assays, iu viro and in viro, the multimers did not have biological activity and inhibitory action to that of CJ 50001. The mutimers did not induce toxicity in mice and rats in acute toxicity test. These results suggest that if Cs970125(300) containing CJ50001 is stored at 5
, CJ50001 will be the multimers that do not have biological activity and inhibitory effect to CJ50001 and do not induce acute toxicity.
A Subchronic Toxicity Study of DA-5018 Creams in Rats
Biomolecules & Therapeutics, volume 6, issue 1, 1998, Pages 95~110
A 13-week dermal toxicity test was conducted to assess the toxicity of DA-5018, a capsaicin derivative. Three groups of Sprague-Dawley rats (10-15 males and 10-15 females) were treated with DA-5018 cream daily by dermal application at concentrations of 0.1%, 0.3% or 0.9% as 500 mg/kg for 13 weeks. One further group of rats (15 males and 15 females) received cream base at 500 mg/kg/day and acted as controls. One male receiving 0.3% DA-5018 cream died during the treatment period. But the animal did not show any signs of treatment-related toxicity until death. There were no local skin reaction of application site and systemic reaction to the treatment of DA-5018 creams in all experimental groups throughout treatment and recovery period. Weight gain and food consumption in animals that received DA-5018 creams appeared to be comparable to that of the controls. Laboratory analyses (hematology, urinalysis and opthalmoscopic examination) did not revealed pathological values. In biochemical investigations, an increase of glucose level associated with increased food consumption and some other significant changes were noted in the animals of both sexes received DA-5018 creams. But these changes were not considered to be of toxicological importance. Postmortem examination did not show macroscopic or histological alterations attributable to the DA-5018 treatments. Based on these results, NOAEL(no-observable-adverse-effect level) of DA-5018 cream if estimated to be over 500 mg/tg/day as 0.9% cream.