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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
> Journal Vol & Issue
Biomolecules & Therapeutics
Journal Basic Information
Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 10, Issue 4 - Dec 2002
Volume 10, Issue 3 - Sep 2002
Volume 10, Issue 2 - Jun 2002
Volume 10, Issue 1 - Mar 2002
Selecting the target year
Protective Effects of Angelica tenuissima Nakai on Hepatotoxicity by Carbon Tetrachloride in Rats
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 211~217
Hepatoprotective activity of methanol extract of Angelica tenuissima Nakai on the
-induced hepatotoxicity was investigated. To elucidate the hepatoprotective activity and free radical scavenging effect, we examined alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, total protein, cholesterol, malondialdehyde (MDA) levels in serum and activities of superoxide dismutase (SOD), catalase (CAT) in hepatic tissue as compared with those of carbon tetrachloride-induced rats. The action mechanism also has been estimated by quantative analysis of cytochrome P450 (CYP), NADPH-CYP reductase for phase I metabolism and glutathion (GSH), glutathion S-transferase (GST) level for phase II metabolsim. Treatment of Angelica tenuissima methanol extract significantly lowered the levels of alanine aminotransferase and aspartate aminotransferase. In addition, the levels of cholesterol, triglyceride, MDA, CAT were decreased, and SOD was activated. This result indicates that the hepatoprotective effect of Angelica tenuissima methanol extract on the CCl4-induced hepatotoxicity would be originated from reduction of the NADPH-CYP reductase, GSH and the enhancement of the activities of GST, CYP.
The Blood-brain Barrier Permeability of Taurine in Senescence-accelerated Mouse and Normal Mouse (ICR)
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 218~223
This study compared the blood-brain barrier permeability of [
] taurine in senescence-accelerated mouse (SAM) and normal mouse with common carotid artery perfusion (CCAP) method and intravenous injection technique to establish a possible relation between aging and changes in tissue levels of taurine. The SAM strains show senescence acceleration and age-associated pathological phenotypes similar to geriatric disorders seen in humans. In the result of this experiments, the plasma clearance of [
]taurine in SAM was almost comparable with that of normal mice by intravenous injection technique, but the brain volume of distribution (
) of [
]taurine in SAM by CCAP method reduced by 85% compared with that in normal mice. These results suggest that aging may have an effect on the brain transport activity of taurine in disease state model animal.
Inhibitory Effects of Simazine on Various Functions of Peritoneal Macrophages
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 224~229
Triazine herbicide has been reported to directly suppress the immune response. In the present study, we examined various functions of murine peritoneal macrophages that were isolated and stimulated with LPS after simazine (300 and 600 mg/kg body weight), a triazine herbicide, was administered every day for 4 weeks. Simazine decreased the capacity of phagocytosis, compared to those of carboxymethylcellulose (CMC)-treated control group. In addition, the production of NO and TNF-
was decrcased in macrophages of simazinetreated mice. However, the production of hydrogen peroxide (
) was not altered. In vitro tumoricidal activity of in vivo simazine-treated macrophages was reduced against target cell. B 16 melanoma. Taken together, these results suggested that simazine might have the immunosuppressive effect on macrophages after in vivo exposure, which was related to the reduction of tumoricidal activity.
Gold Sodium Thiomalate Inhibits iNOS Gene Expression in RAW 264.7 Macrophage: Differential Regulation by Gold Sodium Thiomalate and Sodium Salicylate
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 230~235
Gold sodium thiomalate (GST, gold compound) is a widely used anti-arthritic, anti-rheumatic and anti-inflammatory drug that is considered a good alternative to sodium salicylate (NaSA) for individuals who cannot tolerate salicylates. Nitric oxide (NO) synthesized by inducible nitric oxide synthase (iNOS) has been implicated as a mediator of inflammation. Recent evidence suggests that anti-inflammatory effect of NaSA lies in the inhibition of iNOS, but nothing has been reported about the direct effect of iNOS expression by GST. The present study was designed to elucidate sequentially the action mechanisms of GST and NaSA on lipopolysaccharide (LPS) plus interferon-gamma (IFN-
) induced iNOS expression in RAW 264.7 macrophages. Both GST and NaSA inhibited NO production and iNOS protein expression in a dose dependent manner. GST inhibited iNOS mRNA expression induced by LPS plus IFN-
, whereas NaSA did not. These findings suggest that GST may exert anti-arthritic, anti-rheumatic and anti-inflammatory effect by inhibiting iNOS expression induced by LPS plus IFN-
at transcriptional level, whereas NaSA exert its effect by inhibiting iNOS expression at the translational or posttranslational level.
Antidiarrheal Effect of Lacteol
-Loperamide Combination on Castor oil-induced Mice Model
Hwang, Se-Hee ; Sung, Hee-Jin ; Chung, Yong-Ho ; Ryu, Jei-Man ; Seong, Seung-Kyoo ;
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 236~239
The goal of this study was to evaluate the antidiarrheal efficacy of
-loperamide combination against the mouse model of secretory diarrhea. Secretory dirrhea was induced in mice by p.o. administration of castor oil (0.3 ml). Antidirrheal effects of
-loperamide combination were compared with each individual component.
-loperamide combination was the most potent among these agents, eliminating diarrhea in 100% of mice at a dose 1360/4 mg/kg (Lacteol/loperamide, respectively). In this study, we also measured changes of bodyweight as another indicator of the dirrhea, based on the assumption that lower bodyweight loss represented reduced fecal passage. The bodyweight loss of
-loperamide combination administered group was 4 times lower than that of vehicle control. These findings indicate that
-loperamide combination may be more potent than individual component in its antidiarrheal action, so we are going to challenge this combination for further study and clinical evaluation.
Extracts of Aster species Inhibit Invasive Phenotype and Motility of H-ras MCF10A Human Breast Epithelial Cells Possibly via Downregulation of MMP-2 and MMP-9
Ahn, Seong-Min ; Lee, Kang-Ro ; Moon, A-Ree ;
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 240~245
Cancer metastasis represents the most important cause of cancer death and antitumor agents that may inhibit this process have been extensively pursued. Invasion and metastasis of malignantly transformed cells involve degradation of the extracellular matrix (ECM) components by matrix metalloproteinases (MMP), especially MMP-2 and -9. We previously showed that H-ras-induced invasive phenotype may involve MMP-2, rather than MMP-9, in MCF10A cells. In the present study, we investigated the chemopreventive effect of Aster, a widely used culinary vegetable in Korea. We screened twelve extracts from three Aster species (Aster scaber, Aster oharai and Aster glehni) for the inhibitory effect on MMP activities of H-ras MCF10A human breast epithelial cells. All of the extracts tested in this study efficiently inhibited the gelatinolytic activities of MMP-2 and MMP-9. A more prominent inhibition was observed in MMP-2 activity compared to MMP-9. Out of twelve extracts, eight extracts showed>90％ inhibition of MMP-2 activity in H-ras MCF10A cells while only one extract showed>90％ inhibition of MMP-9 activity. We selected three extracts (AO-3, AG-3 and AS-EA) for further studies since they exerted a marked inhibition in the ratio of MMP-2 to MMP-9. Treatment with AO-3, AG-3 and AS-EA in H-ras MCF10A cells caused a significant inhibition of invasive phenotype and migration, proving a chemopreventive potential of these extracts. Taken together, our results demonstrate that extracts of Aster effectively inhibit invasion and migration of highly malignant human breast cells, possibly via downregulation of MMP-2 and MMP-9.
Studies on the Correlation between SPF Index and Skin Irritation Index of Sunscreens
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 246~252
In recent years, the safety of sunscreens has been challenged based on the reports of their adverse effect on users; dermatitis, allergic contact dermatitis and photo allergic contact dermatitis. The unscientific idea that higher SPF sunsreen is good for health mealeads many users to tend to prefer higher SPF sunscreen. In the toxicological aspect, the need to investigate the safety of sunscreens is steadily increasing. However, there were few studies on the correlation between sun protection factor (SPF) and the safety of sunscreens. The objective of this study was to assess whether there was a correlation between SPF and the safety of sunscreens. We measured in vitro SPF index using homosalate as a standard and examined the toxicity tests such as primary skin irritation tests, ocular irritation test and skin sensitization test. Homosalate (HS), octyl methoxycinnamate (OMC), octyl salicylate (OS), octocrylene (OC) as UVB organic filter and benzophenone-3 (BP3), butyl methoxy dibenzoil methane (BMDM) as UVA organic filter, and titanium dioxide (TD), zinc oxide (ZO) as inorganic filters were used. The skin irritation indexes in rabbits treated with HS, OMC, OS, BP3, and BMDM were significantly increased as SPF indices were increased. Neither ocular irritation in rabbits nor skin sensitization in guinea pigs were increased. It suggests that there might be a good correlation between SPF and the skin irritation indices of organic UV filters and skin irritation might be one of most sensitive index to assess the safety of sunscreens.
The Effect of Achyranthis Radix Extract on Hard Tissure Regeneration
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 253~257
This study was performed to investigate therapeutic effects of Achyranthis Radix extract and chitosan on the growth and differentiation of rat calvarial cells. it was found that treatment of methanol extract of Achyranthis Radix for 2 days caused 2.4-fold increase in the growth of rat calvarial cells. However, chitosan treatment caused only 1.9-fold increase in the cell growth. Treatment of methanol extract of Achyranthis Radix for 14 days caused 2-fold increase in the growth of rat calvarial cells. Alkaline phosphatase activity, one of the markers for bone cell differentiation, was increased approximately by 1.7-fold and 2.9-fold by the treatment of methanol extract of Achyranthis Radix for 2 days and 14 days, respectively. These results suggest that Achyranthis Radix extract could be beneficial for bone regeneration.
General Pharmacology of AS6
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 258~267
In this study the general pharmacological profiles of AS6 on the central nervous system, cardiovascular and the other organs were investigated. The dosages given were 0, 250, 500 and 1000 mg/kg and drugs were orally administered. The animals used for this study were mice, rats and guinea pigs. Significant increases (p<0.01) in the charcoal transport capacity were observed at the high dose of 1000 mg/kg and significant increases in retardation of pain threshold were observed in the test using acetic acid in all dosed animals. However, AS6 showed no noticeable effects on general behavior, motor coordination, spontaneous locomotor activity, hexobarbital-induced sleep time, body temperature, analgesic activity in the test using hot plate method and anticonvulsant activity. Furthermore no noticeable effects were observed in cardiovascular functions in the isolated rat heart, contraction and relaxation of the smooth muscle in the isolated guinea ileum, gastric secretion and renal function.
Genotoxicity Study of HM10411, Recombinant Human Granulocyte Colony Stimulating Factor
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 268~273
Mutagenic potential of HM10411 (recombinant human granulocyte colony stimulating factor) was evaluated by bacterial reverse mutation test, in vitro chromosome aberration test and in vivo micronucleus test. The bacterial reverse mutation test was performed using the histidine auxotroph strains of Salmonella typhimurium TA100, TA1535, TA98, TA1537 and tryptophan auxotroph strain of Escherichia coli WP2 uvrA. The negative results of the bacterial reverse mutation test suggest that HM10411 does not induce mutation, in the genome of Salmonella typhimurium and E. coli under the conditions used. In addition, it has little clastogenicity either in vitro chromosome aberration test or in vivo micronucleus test. For in vitro chromosomal aberration test, Chinese hamster lung(CHL) cells were exposed to HM10411 of 23, 46 or 92
/ml for 6 or 24 hours in the absence and for 6 hours in the presence of metabolic activation system. There was no significant increase in the number of aberrant metaphase in HM 10411-treated groups at any dose levels both in the presence and absence of metabolic activation system. The micronucleus test was carried out using specific pathogen free(SPF) 7-week old male ICR mice, The test item, HM10411 was intraperitoneally administered at 1150, 2300 or 4600
/kg once a day for 2 consecutive days. There was no significant increase in the frequencies of micronucleated polychromatic erythrocytes(PCEs) at any treated groups compared with negative control group. Therefore, these results demonstrate that the test item, HM10411, was not mutagenic under the condition of these studies.
Relationship between Concentrations and Phototoxicity of Fluoroquinolones in Mice
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 274~280
The fluoroquinolones have been reported to cause, although at low frequency, severe phototoxicity which is due to singlet oxygen produced by ultraviolet-A (UVA; 320-400 nm) exposure. The objective of this study was to evaluate the phototoxicity based on plasma and tissue concentrations of commonly prescribed fluoroquinolones; lomefloxacin (LFLX), enoxacin (ENX), ofloxacin (OFLX), and ciprofloxacin (CPFX). The phototoxic potentials were investigated by measuring increments in ear thickness, 24 hrs after these fluoroquinolones were orally administered to Balb/c mice, which they were exposed to UVA 17.5 J/
for 2 hrs following drug administration. The fifty percent ear thickness increment-inducing doses (
), determined by single ascending dosing of each fluoroquinolone to mice, were calculated to be 50(LMFX), 250(ENX), 770(OFLX), 1100(CPFX) mg/kg. Post the administration of ETID
, drug concentrations in plasma and ear tissue were measured at specified times and phototoxicities were quantified. Both peak plasma (
/ml) and ear tissue (
/g) concentrations were summarized as follows; 7.3/1.4 for LMFX, 15.0/1.6 for ENX, 90.1/18.4 for OFLX and 87.2/3.7 for CPFX. The degree of photo toxicity was more relevant to plasma concentrations than tissue concentrations. In order to assess the effect of irradiation time after drug administration on phototoxicity, the 2 hr UVA irradiation was given at 0, 1, 2, 3, and 5 hr after administering
, respectively and photo toxicities were evaluated. The shorter inteval between dosing and UVA exposure was, the higher risk of phototoxicity was produced.d.
Studies on the Air-Liquid Interface Culture as an Experimental Model for Physiology and Pharmacology of Tracheal Epithelial Cells
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 281~286
In this study, we intended to get a preliminary data for establishing rat tracheal surface epithelial(RTSE) cell culture system as an experimental model for physiology and pharmacology of tracheal epithelial cells. Primary culture on the membrane support and application of the air-liquid interface system at the level of cell layer were performed. The cell growth rate and mucin production rate were measured according to the days in culture. The results were as follows: this culture system was found to manifest mucocilliary differentiation of rat tracheal epithelial cells, the cells were confluent and the quantity of produced and released mucin was highest on culture day 9, the mucin was mainly released to the apical side and tbe free
-glucosamine which was not incorporated to process of synthesis of mucin was left on the basolateral side. Taken together, we suggest that air-liquid interface culture system can be used as a substitute for immersion culture system and as an experimental model for in vivo mucus-hypersecretory diseases.
Cytotoxic Activities and Antioxidative Activities Against Liver Cancer Cell of Albizzia root
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 287~292
To find new inhibitory effects from oriental drugs, Albizziae root was extracted in methanol and the extracted was stepwisely fractionated by hexane, chloroform, ethylacetate, butanol and water. In cytotoxic effect of Albizziae root fractions against cancer cell lines including human hepatoma cells(HepG2) were investigated. Expecially the butanol fraction exhibited a inhibition effects on the growth of human hepatoma cells(HepG2). It inhibited of HepG2 cells with the value of IC50. The activities of qutathione after B(a)P treatment were markedly decreased than control, but those levels were increased by the treatment of Albizziae root methanol fraction. The activity of glutathione-S-transferase after B(a)P treatment were markedly decreased than control, but those levels were increased by the treatment of Albizziae root methanol traction. Induction of phase II enzymes is a major mechanism of chemoprevention. The induction levels of quinone reductase(QR) activity in cultured murine hepatoma(Hepa IcIc7)cell by methanol extract of Albizziae root were measured. Among the tested tractions, the extracts of butanol were found to induce QR activities over 2.8 fold than control. These results suggest that Albizziae root has chemopreventive Potential by inducing QR activities and GST levels and increasing GSH
Metal Ion Transporters Identified in Recent Studies
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 293~302
The classical concept for iron uptake into mammalian cells has been the endocytosis of transferrin(
receptor cycle. In this case, we could not explain the uptake of F
ion and the export of iron from endosome. Studies on iron transport revealed that other transport system exists in epithelial cells of the intestine. One of non-
-receptor-mediated transport systems is Nramp2/DMT1/DCT1 which transports M
ion as well as F
ion. DMT1 was cloned from intestines of iron-deficient rats and shown to be a hydrogen ion-coupled iron transporter and a protein regulated by absorbed dietary iron. DMT1 is founded in other cells such as cortical and hippocampal glial cells as well as endothelial cells in duodenum. Two F
ion bound to transferrin(
) are taken up via the
receptor cycle in the intestinal epithelial cell. F
in endosome was converted to F
ion, and then exported to cytosol via DMT1. F
ion is taken up into cytosol via DMT1. Several other transporters such as FET, FRE, CCC2, AFT1, SMF, FTR, ZER, ZIP, ZnT and CTR have been reported recently and dysfunction of the transporters are related with diseases containing Wilson's disease, Menkes disease and hemochromatosis. Evidences from several studies strongly suggest that DMT1 is the major transporter of iron in the intestine and functions critically in transport of other metal ions.
Bioequivalence of Shinil Cefadroxil Capsule to Duricef Capsule (cefadroxil 500 mg)
Biomolecules & Therapeutics, volume 10, issue 4, 2002, Pages 303~308
A bioequivalence study of Shin II Cefadroxil capsule (Shin II Pharm. Co. Ltd.) to Duricef capsule(Bo Ryung Pharm. Co. Ltd.), each containing 500 mg of cefadroxil, was conducted. Twenty three healthy Korean male subjects administered each formulation at the dose of 1 capsule (500 mg as cefadroxil) in 2
2 cross-over study. There was a I-week washout period between the doses. Plasma concentrations of cefadroxil were monitored for a period of 8 hr after each administration by an LC/UV method. Area under the plasma concentration-time curve up to 8 hr (
) was calculated by a linear trapezoidal method.
was compiled from the plasma drug concentration-time data. ANOVA test was conducted for logarithmically transformed
The results showed that there are no significant differences in
between the two formulations: The differences between d1e formulations in these log transformed parameters were all for less than 20% (i.e., －0.57%, 3.84% for
, respectively). The 90% confidence intervals for the log transformed data were within the acceptance range of log 0.8 to log 1.25 (i.e., log 0.94~log 1.04 and log 0.95~log 1.10 for
, respectively). Based on d1e bioequivalence criteria of KFDA guidelines, the two formulations of cefadroxil were concluded to be bioequivalent.