• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.469-476
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• 2010

This study was to investigate the effect of apigenin on the bioavailability of paclitaxel after oral and intravenous administration in rats. The effect of apigenin on P-glycoprotein (P-gp), cytochrome P450 (CYP)3A4 activity was evaluated. The pharmacokinetic parameters of paclitaxel were determined in rats after oral (40 mg/kg) or intravenous (5 mg/kg) administration of paclitaxel with apigenin (0.4, 2 and 8 mg/kg) to rats. Apigenin inhibited CYP3A4 activity with 50% inhibition concentration ($IC_{50}$) of 1.8 ${\mu}M$. In addition, apigenin significantly inhibited P-gp activity. Compared to the control group, apigenin significantly increased the area under the plasma concentration-time curve (AUC, p<0.05 by 2 mg/kg, 59.0% higher; p<0.01 by 8 mg/kg, 87% higher) of oral paclitaxel. Apigenin also significantly (p<0.05 by 2 mg/kg, 37.2% higher; p<0.01 by 8 mg/kg, 59.3% higher) increased the peak plasma concentration ($C_{max}$) of oral paclitaxel. Apigenin significantly increased the terminal half-life ($t_{1/2}$, p<0.05 by 8 mg/kg, 34.5%) of oral paclitaxel. Consequently, the absolute bioavailability (A.B.) of paclitaxel was significantly (p<0.05 by 2 mg/kg, p<0.01 by 8 mg/kg) increased by apigenin compared to that in the control group, and the relative bioavailability (R.B.) of oral paclitaxel was increased by 1.14- to 1.87-fold. The pharmacokinetics of intravenous paclitaxel were not affected by the concurrent use of apigenin in contrast to the oral administration of paclitaxel. Accordingly, the enhanced oral bioavailability by apigenin may be mainly due to increased intestinal absorption caused via P-gp inhibition by apigenin rather than to reduced renal and hepatic elimination of paclitaxel. The increase in the oral bioavailability might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced first-pass metabolism of paclitaxel via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by apigenin. It appears that the development of oral paclitaxel preparations as a combination therapy is possible, which will be more convenient than the i.v. dosage form.

• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.67-76
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• 1990

Hydrocortisone 50 mg/kg (HC), dehydroepiandrosterone 250 mg/kg (DHEA), ${\beta}-estradiol$ 5 mg/kg (E2), and testosterone 20 mg/kg (TS) were subcutaneously injected into the castrated ICR mice at noon for four days, and the animals were sacrificed at 10-12 A.M. of the fifth day. The intestinal DAO activity was significantly decreased by HC, but it was rather increased by E2 and TS, respectively. And DHEA did not change the DAO activity. But the hepatic MAO activity was not affected by anyone of HC, DHEA, E2, and TS. Aminoguanidine 25 mg/kg produced the marked decrease of the intestinal DAO activity and the significant increases of the intestinal PT and SD contents, but it did not change the hepatic polyamine contents. HC and DHEA induced the significant increase of the intestinal PT content. E2 induced the marked increase of the hepatic PT content and the moderate increase of the intestinal PT content. TS little affected the polyamine contents of the liver and intestine. These results suggest that the E2-induced increase of the hepatic PT content is rather ascribed to the greater enhancement of PT synthesis than the inhibition of polyamine catabolism, and that the HC-induced increase of the intestinal PT content is due partly to the inhibition of polyamine catabolism via DAO.

• The korean journal of orthodontics
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• v.30 no.6 s.83
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• pp.723-730
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• 2000

Orthodontic tooth movement requires remodelling of periodontal tissues, especially alveolar bone. Fluoride is known to be a potent inhibitor of osteoclastic bone resorption. The purpose of this study was to examine the effects of a consumption of fluoride on osteoclast numbers appearing on the pressure side of alveolar bones at experimental tooth movement. 40 male rats were exposed to 0, 10, 25 mg/kg/day of sodium fluoride(NaF) in their drinking water for up to 60 days. Orthodontic appliance were activated to mesially tip maxillary first molar with 50-70g. The rats were sacrificed at 1, 2, 4 days after initial activation. The number of osteoclast was counted in a $450\times700\;{\mu}m^2$ area interradicular septum on the pressure side of the maxillary first molar. The results were as fellows, 1. There was significantly different osteoclast number between control group and 25 mg/kg/day group at all measured time. (p<0.05) 2. There was significantly different active bone-resorption area between control group and 25 mg/kg/day group except at 96 hours post activation. (p<0.05) 3. There was slight reduction of active bone- resorption area in control group from 48 hours to 96 hours but in both 10 mg/kg/day group and 25 mg/kg/day group a slight increase was observed from 48 hours to 96 hours.

• Food Science and Preservation
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• v.14 no.5
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• pp.545-551
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• 2007

Bacillus sp. SP-KSW3 is an auxothroph bacteria that is being used for starter in fermentation. Physico-chemical characteristics, enzyme activities, ACE inhibitor and antimutagenicity in fermented soybean inoculated with Bacillus sp. SP-KSW3 starter was investigated for the ripening duration of fermentation. Tyrosinase and ACE showed 10% higher activity degree on test field than control. for antimutagenicity using S. enterica serovar Typhimurium TA100 against MNNG and NPD showed 86.24% and 75.63% Similarly, S. enterica serovar Typhimurium TA98 was used against NPD and NQO showed 60.28% and 50.92% respectively. Hydrogen donating ability increased compared to the control having 81.7% and 80.1% respectively. Daidzin of isoflavone in fermented soybean showed higher concentration in control than in the test field. Genistein from two years of ripening test field contained 11.67 mg/kg compared to the test field. The initial test field for daidzin contained 389.96 mg/kg which increased to 453.67 mg/kg after two years and the initial genistein contained 402.68 mg/kg which also increased to 556.86 mg/kg.

• Toxicological Research
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• v.25 no.3
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• pp.147-157
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• 2009

This study was conducted to obtain acute information of the oral dose toxicity of lyophilized water extract of Pinelliae Rhizoma, a dried tuber of Pinellia ternata (PR) in male and female mice. In order to calculated 50% lethal dose (LD$_{50}$) and approximate lethal dose (ALD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250, 125 and 0 (vehicle control) ml/kg (body weight). The mortality and changes in body weight, clinical signs, gross observation, organ weight and histopathology of principle organs were monitored 14 days after treatment with PR extract. We could not find any mortalities, clinical signs, changes in the body and organ weights, gross and histopathological findings except for dose-dependent increases in the hepatic fatty change frequencies detected in PR extract 2000 and 1000mg/kg treated in both male and female mice. The results obtained in this study suggest that LD$_{50}$ and approximate LD in mice after single oral dose of PR extracts were considered over 2000 mg/kg in both and female male mice, but more than 1000mg/kg of PR extracts treatment could induce slight hepatotoxicity the fatty changes in mice.

• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.384-389
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• 1997

Neutropenia is a major dose-limiting side effect of cancer chemotherapy. The therapeutic effects of CJ-50001 were examined on neutropenia caused by anticancer agents. Neutropenia was induced by cyclophosphomide (130 mg/kg), doxorubicin (4.5 mg/kg), and vincristine (1 mg/kg) in normal ICR mice and by cyclophosphamide (200 mg/kg) in CT26 adenocarcinoma bearing BALB/C mice. After the subcutaneous injection of anticancer agents, we administered subcutaneously recombinant human granulocyte-colonystimulating factor (100$\mu$g/kg/day) to mice in order to stimulate neutrophil production. In normal and tumor-bearing mice, neutrophil production efficacy of CJ-50001 (rG-CSF) was similar to that of Grasin. These results suggest that CJ-50001 could be effective in its clinical use for neutropenia treatment.

• The Korean Journal of Pesticide Science
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• v.5 no.1
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• pp.12-18
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• 2001

The effects of organophosphorus were examined with inhibition of the cholinesterase activity on tile chicken plasma in vivo and in vitro. The cholinesterase activity in chicken plasma determined by tile Ellman mettled was $23{\mu}mol$/min/g protein. After oral administration with 0.2 and 0.5 times of organophosphorus terbufos $LD_{50}$(1.81 mg/kg), cholinesterase activity were inhibited to 36% and 96% of control after 15min in vivo, respectively. After oral administration with 0.2 and 0.5 times of terbufos $LD_{50}$(1.81 mg/kg), then the recovery of cholinesterase activity followed to 99% and 56% of control after 11hr, respectively. Ki of phosphorodithioate and phosphorothioate with P=S was $74{\sim}322\;mole^{-1}min^{-1}$ in vitro. Ki of phosphate and phosphorothiolate with P=O was $13898{\sim}79610\;mole^{-1}min^{-1}$. Toxicology of organophosphorus with P=S was higher than that of organophosphorus with P=S by oxidation. $pI_{50}$ of phosphorodithioate and phosphorothioate with P=S was $21{\sim}102$ mg/L. $pI_{50}$ of phosphate and phosphorothiolate with P=O was $0.519{\sim}0.071$ mg/L. Enzyme-Inhibition method with cholinesterase was the rapid bioassay method to detect the organohpophorus pesticides in vitro.

• The Journal of Internal Korean Medicine
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• v.31 no.2
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• pp.224-241
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• 2010

Objectives : The aim of the current study was to investigate the effects of Sargassum (Sargassum pallidum (TURN.) C. AG.; SP) on the experimental colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. Methods : ICR mice were divided into 7 groups (NOR, CON, $SS50\times5$, $SP20\times3$, $SP50\times3$, $SP20\times5$, $SP50\times5$). TNBS processing was intrarectally applied to all experimental groups on the 3rd experiment day, except the normal group (NOR). For investigating the prophylactic effect, SP at doses of 20 mg/kg ($SP20\times5$) and 50 mg/kg ($SP50\times5$) were orally administered for 5 days. The SP at doses of 20 mg/kg ($SP20\times3$) and 50 mg/kg ($SP50\times3$) were orally administered for 3 days after the colitis induction in order to check the effect of treatment. As a positive control group, sulfasalazine 50 mg/kg ($SS50\times5$) was administrated. Macroscopic findings of epithelial tissue on mice were measured by colon length and macroscopic score. Histologic findings were also checked by crypt cell, epithelial cell, inflammatory cell and edema of submucosa. We measured the ability of SP to inhibit lipid peroxidation and myeloperoxidase activity. We also measured levels of the inflammatory markers, interleukin (IL)-$1\beta$ and cyclooxygenase-2 (COX-2), its transcription factor activation, phospho-NF-${\kappa}B$ (pp65), in the colon by enzyme-linked immunosorbent assay and immunoblot analysis. We measured activation of fecal bacterial enzyme, $\beta$-glucuronidase and degradation activation of fecal glycosaminoglycan (GAG), and hyaluronic acid. Results : Oral administration of SP on mice inhibited TNBS-induced colon shortening and myeloperoxidase activity in the colon of mice as well as IL-$1\beta$ and COX-2 expression. SP also inhibited TNBS-induced lipid peroxidation and pp65 activation in the colon of mice. SP inhibited $\beta$-glucuronidase activation and fecal hyaluronic acid degradation activation as well. Conclusions : SP could be a possible herbal candidate and preventive prebiotic agent for treating inflammatory bowel disease (IBD). Further experiments to differentiate effects of SP on IBD, such as other solutions and extracting times, might be promising.

• Biomolecules & Therapeutics
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• v.15 no.1
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• pp.40-45
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• 2007

The vascular relaxant effects on isolated rat aorta of amlodipine camsylates (S-, R-enantiomer, and R/S-racemate), were evaluated and compared with that of S-amlodipine besylate. Furthermore, antihypertensive effects were measured in spontaneously hypertensive rat (SHR). The S-amlodipine camsylate concentration-dependently inhibited $Ca^{2+}$-induced contraction of rat aorta with a very slow onset of action (reached its maximum at 3.5h; $ED_{50}:\;1.50\;{\pm}\;0.24$ nM), having a potency 2-fold higher than those of R/S-amlodipine camsylate $(ED_{50}:\;3.36\;{\pm}\;0.91\;nM)$ and similar to those of S-amlodipine besylate $(ED_{50}:\;1.44\;{\pm}\;0.14\;nM)$, whereas the R-amlodipine camsylate has 590-fold lower vasorelaxant activity $(ED_{50}:\;886.4\;{\pm}\;49.7\;nM)$. In SHR, orally administered S-amlodipine camsylate produced a dose-dependent and long-lasting (>>10 h) antihypertensive effect $(ED_{20}:\;0.89\;mg/kg)$, with a potency 2-fold higher than those of R/S-amlodipine camsylate $(ED_{20}:\;1.82\;mg/kg)$ and similar to those of S-amlodipine besylate $(ED_{20}:\;0.71\;mg/kg)$. In contrast, the R-amlodipine camsylate has no effect even-though administrated high concentration 10 mg/kg. These results suggest that S-amlodipine camsylate has the potency and long-lasting antihypertensive activity as single enantiomer drug, and its antihypertensive effect is not significantly different to that of S-amlodipine besylate.

• KSBB Journal
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• v.20 no.2 s.91
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• pp.84-87
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• 2005

Toxicity test for biodiesel (BD), biodiesel-derived neopentyl polyol ester (NPE) lubricant oil base, lubricant oil for diesel engine oil (LODE) and petroleum diesel (PD) was carried out using earthworm, Eisenia fefida. According to the method by OECD 207, the $LC_{50}$ values of BD and NPE were estimated as 2,450 and 1,528 mg/kg, respectively, which indicate that these compounds are classified as slightly toxic compounds. The $LC_{50}$ values of LODE and PD were estimated as 500 and 603mg/kg, respectively, showing that theses compounds are evaluated as moderately toxic compounds.