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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 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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Vaccine Development-Biotechnological Applications
Biomolecules and Therapeutics, volume 3, issue 1, 1995, Pages 1~11
Oral Subacute Toxicity of Nongenotoxic Hepatocarcinogen, Clofibrate in F344 Rats
Biomolecules and Therapeutics, volume 3, issue 1, 1995, Pages 12~20
Clofibrate, a peroxisome proliferator, is hepatocarcinogenic in rats in a dose-dependent manner. A total of 70 male and female F344 rats, 5-week-old, were divided into three groups. Rats were fed clofibrate at 0, 0.25, or 0.5% in diet for 30 days. All rats were anesthetized with
, blood samples were taken by cardiac puncture for hematology and clinical chemistry, and the rats were killed by exsanguination. Livers, kidenys, pancreas, adrenal glands, spleen, heart, lungs, thyroid gland, reproductive organs, and digestive organs were removed, weighed, later processed, and embedded with paraplast for histological examination. The relative liver and kidney weights with respect to final body weight in the clofibrate-treated group were significantly increased compared with those of control group at all dose levels (p<0.01). It has been suggested that clofibrate may influence on hepatotoxicity by increases in peroxisomal proliferation.
Receptor Binding Analysis for Drug Screening
Lee, Sunghou ; Lee, Buyean ; Hwasup Shin ; Jaeyang Kong ;
Biomolecules and Therapeutics, volume 3, issue 1, 1995, Pages 21~27
The only compounds with antagonistic activity via AT
receptor, one of two subtypes of angiotensin II (AII) receptor, have been demonstrated to block the vasoconstriction effects of AII and thereby provide therapeutic potential. This initiated the search for compounds with high specific affinity to AT
receptor and their effective screening methods. The radioligand binding assay for the AII receptor is regarded as the primary method for the evaluation of AT
receptor antagonists for their activity. In this paper, we characterized the liver AT
receptor and describe the efficient method of the radioligand binding assay using rat liver as a source of AT
receptor. Equilibrium binding studies with rat adrenal cortex, adrenal medulla, liver and bovine adrenal showed that the specific bindings of [
H] AII were saturable in all tissues and the Scatchard plots of those data were linear, suggesting a single population of binding sites. Hill slopes were very near to the unity in all tissues. Kinetic studies of [
H) AII binding in rat liver homogenates yielded two association rate constants, 4.10
, with a single dissociation rate constant, 7.07
, possibly due to the partial dissociation phenomenon. The rank order of inhibition potencies of [
H] AII binding in rat liver was AII>Sarile>Losartan>PD 123177. Rat liver homogenates revealed to have very high density of homogeneous population of the AT
receptor subtype, as the specifically bound [
H] AII was not inhibited by PD 123177, the nonpeptide antagonist of AT
. The results of this study demonstrated that the liver homogenates from rats could be the best receptor preparation for the AT
receptor binding assay and provide an efficient system for the screening of newly synthesized candidate compounds of AT
Effects of Ginkgo biloba Leaf Extracts on the bevels of Neurotransmitters in the Spontaneously Hypertensive Rat Brain
Biomolecules and Therapeutics, volume 3, issue 1, 1995, Pages 28~33
Effects of Ginkgo biloba leaf extract (GBE) and its components kaempferol-coumaroyl glucosyl rhamnoside (Kc), quercetin-coumaroyl glucosyl rhamnoside (Qc), ginkolide (G) and bilobalide (B) on blood pressure and on the levels of neurotransmitters in the spontaneously hypertensive rat brain were examined. Blood pressure decreased about 10 mmHg after administration of GBE but without significance. The concentration of norepinephrine increased (3 times) and that of DOPAC was decreased (38%) after administration of Qc. And 3-MT concentration was increased (36%) by Kc administration in striatum. While Qc administration increased the concentration of Ach (260%) and Ch(29%) significantly, B administration increased Ch concentration in cerebral cortex.
Inhibition of Thymidylate Synthase by Non-Steroidal Anti-Inflammatory Drugs
Cho, Sung-Woo ; Park, Soo-Young ; Kim, Tae ue ;
Biomolecules and Therapeutics, volume 3, issue 1, 1995, Pages 34~37
Non-steroidal anti-inflammatory drugs (NSAIDs) have been known as inhibitors of the folate-requiring enzymes. In the present work, we have expanded on these observations and have investigated the inhibitory effects of NSAIDs on Lactobacillus casei thymidylate synthase expressed in E. coli. NSAIDs including sulphasalizine, salicylic acid, indomethacin and mefenamic acid were found to be competitive inhibitors with respect to folate of Lactobacillus casei thymidylate synthase. In contrast, aspirin and the antipyretic-analgesic drugs acetaminophen and antipyrine were weak inhibitors of the enzyme. Structure-activity correlation suggests that an aromatic ring with a side chain containing a carboxylic acid is a requirement for competitive inhibition of the thymidylate synthase. The results are consistent with the hypothesis that the antifolate activity of NSAIDs, and hence cytostatic consequences, are important factors in producing anti-inflammatory activity and aspirin exerts its anti-inflammatory effects after its conversion into salicylic acid, which possesses greater antifolate activity than its parent compound.
Reproductive Toxicity of DA-125, A New Anthracycline Anticancer Agent: Peri- and Postnatal Study in Rats
Biomolecules and Therapeutics, volume 3, issue 1, 1995, Pages 38~46
DA-125, a new anthracycline antitumor antibiotic, was administered at dose levels of 0, 0.04, 0.2 and 1.0 mg/kg/day intravenously to pregnant and subsequently delivered Sprague-Dawley rats from day 17 of gestation to day 21 of lactation. Effects of test agent on general toxicity of dams and growth, behaviour and mating performance of F1 offspring were examined. At 1 mg/kg, one out of the twentytwo dams showed difficult delivery, characterized by a stillbirth. Reduction in body weight, loss in food intake, and decrease in spleen weight were also observed in dams. In addition, the lower rates of successful performances in memory test (28.6%) and necrosis of tail end (9.5%) were seen in F1 offspring. At 0.04 and 0.2 mg/kg, no toxic effect on dams and F1 offspring was observed. There were no malformed Fl and F2 fetuses in all groups. The results indicate that the no effect dose levels(NOELs) of DA-125 are 0.2 mg/kg/day for dams and Fl offspring, and over 1 mg/kg/day for F2 fetuses.
Reproductive Toxicity of DA-125, A New Anthracycline Anticancer Agent: Teratogenicity Study in Rabbits
Biomolecules and Therapeutics, volume 3, issue 1, 1995, Pages 47~53
DA-125, a new anthracycline antitumor antibiotic, was administered at dose levels of 0, 0.2, 0.6 and 1.8 mg/kg/day intravenously to pregnant New Zealand White rabbits from day 6 through 18 of gestation. The does were subjected to the caesarean section on day 28 of gestation. Effects of test agent on general toxicity of does and embryonic development of F1 fetuses were examined. At 1.8 mg/kg, the organ weight for ovary of does was significantly decreased. The decrease in the number of corpus lutea, implantations and litter size, and the increase in the rate of resorptions were also observed. In addition, various types of external, visceral and skeletal malformations occurred in fetuses at an incidence of 7.7, 7.7 and 20.6%, respectively. The results show that the no effect dose levels (NOELs) of DA-125 are 0.6 mg/kg/day for does and F1 fetuses.
The Effect of Ruthenium Red on the Capsaicin-Induced Antinociception in vivo
Lee, Bu-Yean ; Jung, Yi-Sook ; Choi, Jin-Il ; Kong, Jae-Yang ;
Biomolecules and Therapeutics, volume 3, issue 1, 1995, Pages 54~57
The effect of Ruthenium Red on the antinociceptive action of capsaicinoids was investigated using tail-flick test in mice. Capsaicin and KR-25018, when administered subcutaneously, had a potent antinociceptive effect against noxious heat stimulus. Ruthenium Red which is known to block the calcium channel coupled to the capsaicin receptor, when injected intraperitoneally more than 5 mg/kg, showed severe sedation and apparent antinociceptive effect against noxious heat stimulus. The 2.5 mg/kg Ruthenium Red, at which dose any significant sedative effect was not shown, had no effect on the antinociceptive effects of capsaicin and KR-25018. Considering this result, the antinociceptive effect of capsaicinoid may not be related to the Ruthenium Red sensitive calcium channel which is activated by capsaicin.
Is Nitric Oxide Involved in Relaxation of Urinary Bladder\ulcorner
Chang, Ki-Churl ; Chung, Byung-Ha ;
Biomolecules and Therapeutics, volume 3, issue 1, 1995, Pages 58~62
We investigated whether nitric oxide (NO) may serve a role in bladder function by immunohistochemical analysis of the distribution of intrinsic NADPH-diaphorase and functional study of isometric tension recordings via a photo-induced adequate nitric oxide (PIANO) generating system using rat bladder. Results suggest that a small number of NADPH-diaphorase-positive perikarya are present within the bladder wall and within adjacent small ganglia. Furthermore, NADPH-diaphorase-positive nerve fibers were observed in the adventitial and muscular layers, subjacent to the urothelium and perivascular fibers. Rat bladder strips precontracted with 3
M carbachol were reversibly relaxed upon NO generation by UV irradiation. PIANO-mediated relaxation was sensitive to oxygen free radicals. In addition, tissue cGMP levels were increased by the PIANO generating system and elevated cGMP levels were decreased by pretreatment of guanylate cyclase inhibitor, methylene blue. These results indicate that NO may serve a role in modulating bladder tone in the rat.
Local Irritation of DA-3002, an Authentic Recombinant Human Growth Hormone, in Rabbits
Biomolecules and Therapeutics, volume 3, issue 1, 1995, Pages 63~71
The local irritation studies of DA-3002, an authentic recombinant human growth hormone (rhGH), were carried out in rabbits after the following treatment ; application into the conjunctival sac of the eye (single), single subcutaneous and intramuscular injection, 7-day repeated subcutaneous and intramuscular injection. The results obtained were as follows. In the result of ocular irritation test, 0.16% solution of DA-3002 could be considered as a non-irritating material. In single subcutaneous and intramuscular irritation test, the irritancy of 0.16% DA-3002 solution was not so much different from that of saline. The local irritation of DA-3002 by 7-day repeated injection was negligible and similar to that of saline by both subcutaneous and intramuscular routes. These results suggest that DA-3002 has no irritating activity when injected through subcutaneous or intramuscular route for clinical practice as 0.16% solution.
Studies on the Synthesis and Biological Activity of Prostaglandin Derivatives II. Effects of Prostaglandin Derivatives on Acute Gastric Ulcer and Gastric Secretion in Rats
Biomolecules and Therapeutics, volume 3, issue 1, 1995, Pages 72~79
The antiulcer effects of newly synthesized prostaglandin derivatives were investigated in various experimental ulcer models and on gastric secretion in rats. HK-3 and HK-4, PG
derivatives, prevented the formation of acute gastric ulcer induced by ethanol or aspirin in pylorus-ligated rats. The ulcer formation was moderately inhibited by HK-1 and HK-2, PG
derivatives, and aggravated by SK-1, SK-2 and SK-3, PG
derivatives. HK-3 and HK-4 reduced the volume, acid output and pepsin output of gastric juice in pylorus-ligated rats. The gastric perfusion with physiologic saline(pH 6.0) showed relatively constant acid secretion and indomethacin increased the acid secretion. The acid secretion was markedly decreased by PG
caused little change. Prostaglandin derivatives, especially HK-3 arid HK-4, significantly inhibited the acid secretion induced by indomethacin. The results show that, PG
derivatives, HK-3 and HK-4, inhibit acid secretion and also have protective effects on gastric ulceration induced by ethanol or aspirin.
Effects of Titrated Extract of Centella asiatica and Epidermal Growth Factor on the Proliferation of Human Epidermal Keratinocyte
Biomolecules and Therapeutics, volume 3, issue 1, 1995, Pages 80~84
Effects of titrated extract of Centella asiatica (TECA) and epidermal growth factor (EGF) isolated from the urine of pregnant horse on the proliferation of human epidermal keratinocyte in culture were studied. An increase in the number of keratinocyte was observed with the treatment of TECA at the concentration ranges from 1
/mι to 100
/mι. Effects of low molecular weight EGF (LEGF) and high molecular weight EGF (HEGF) on the proliferation of keratinocyte in culture were also studied. The number of keratinocyte in culture was significantly increased with LEGF and HEGF respectively at the concentration of 10 ng/mι. Simultaneous treatment of the keratinocyte with LEGF, HEGF and TECA led to the increased proliferation of keratinocytes resulting 96% of the effect of a positive control, EGF isolated from mouse submaxillary glands.
Alteration of Hepatic 3'-Phosphoadenosine 5'-phosphosulfate and Sulfate in ICR Mice by Xenobiotics that are Sulfated
Kim, Hyo-Jung ; Oh, Mi-Hyune ; Sunwoo, Yu-Sin ; Seo, Kyung-Won ; Park, In-Won ; Moon, Byung-Won ;
Biomolecules and Therapeutics, volume 3, issue 1, 1995, Pages 85~90
Phenol, acetaminophen (AA) and salicylamide are all known to be sulfated in rats and mice. We have previously demonstrated that capacity-limited sulfation of xenobiotics in rats is due to the reduced availability of hepatic 3'-phosphoadenosine 5'-phosphosulfate (PAPS), the cosubstrate for sulfation, which in turn is limited by the availability of its precursor, inorganic sulfate. Because species differences have been reported in the extent of sulfation, this study was conducted to determine whether these xenobiotics lower hepatic PAPS and sulfate in ICR mice. All three substrates decreased serum sulfate concentrations in a dose- and time-dependent manner. However, contrary to the observations in rats, phenol markedly increased hepatic PAPS concentrations in a dose-dependent manner, 1 hr after ip injection of 0∼4 mmol/kg. Following ip injection of 4 mmol/kg phenol, hepatic PAPS concentraions were enhanced 2∼3 fold, 0.5-2 hr after dosing and returned to control values 3 hr after dosing, whereas AA and salicylamide had little effect on hepatic PAPS concentraions. In summary, these studies demonstrate that phenol markedly enhances hepatic PAPS concentrations in mice, whereas hepatic PAPS levels are not affected by AA and salicylamide. Our data suggest that 1) hepatic sulfation for high dosages of xenobiotics in ICR mice is not limited by the availability of cosubstrate and 2) there are significant species differences in the regulation of PAPS between rats and mice.
Changes of Amino Acid Neurotransmitter Contents in Rat Brain by Toluene Inhalation
Biomolecules and Therapeutics, volume 3, issue 1, 1995, Pages 91~96
The effects of toluene inhalation on the contents of amino acid neurotransmitters in rat brain were investigated and blood toluene concentrations inducing changes of behavior and amino acid neurotransmitter contents in rat brain were observed. Male wistar rats were exposed to toluene vapor (single dose : 1700, 5000 and 10000 ppm for 2 hrs, repeated dose : 1700 and 5000 ppm for 2 hrs/day
6 days). Toluene concentrations in blood and the inhalation chamber were assayed by GC with headspace sampler. HPLC method following PITC derivatization was used to measure the amino acid contents in brain tissues such as frontal cortex, caudate, hippocampus, cerebellum and brain stem. Glutamic acid and aspartic acid levels were increased by single inhalation of toluene (5000 ppm) in all the brain areas assayed in this experiment. In caudate and cerebellum, taurine levels were decreased by single inhalation of low dose toluene (1700 ppm), but increased by repeated administration. At high blood toluene concentration, GABA levels were increased in all the brain areas assayed in this experiment and the increasing extents of inhibitory amino acid contents measured in caudate and hippocampus were greater than those of excitatory amino acids. These results suggest that the changes of amino acid neurotransmitter contents in brain by exposure to toluene may modulate toluene-induced behaviors.