• YAKHAK HOEJI
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• v.39 no.4
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• pp.450-460
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• 1995

The acute toxicity of fthalide in rat was studied in vivo by the observations of the changes in hematogram, serological parameters, content of cytochrome p-450, activities of NADPH-cytochrom c reductase, glucose-6-phosphatase, and the contents of cholinesterase and carboxylesterase in liver. Fthabde is a practically non-toxic substance(LD50 is 3.86g/kg), but rats were intoxicated with fthabde at a oral dose of 100 mg/kg for 12 days. WBC were significantly decreased and activities of ALT and LDH, on the cotrary, the content of glucose in serum were slightly increased. Cytochrome p-450 and lipid peroxide in liver were significantly increased in the fthalide-intoxicated rats. The longer administration of fthalide showed further increase of carboxylesterase activity in liver and serum, but decrease of activities of glucose-6-phosphatase and cholinesterase in liver and serum. These results show that fthatide can induce the hepatocellular injury and neurotoxicity.

• Proceedings of the Zoological Society Korea Conference
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• 1996.10a
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• pp.144.1-144
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• 1996

No Abstract, See Full Text

• BMB Reports
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• v.38 no.5
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• pp.619-623
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• 2005

The efficacy of chemotherapeutic agents on tumor cells has been shown to be modulated by tumor suppressor gene p53 and its target genes such as Bcl-2 family members (Bax, Noxa, and PUMA). However, various chemotherapeutic agents can induce cell death in tumor cells that do not express the functional p53, suggesting that some chemotherapeutic agents may induce cell death in a p53-independent pathway. Here we showed that etoposide can induce the similar degree of cell death in p53-deficient HCT 116 cells, whereas 5'-FU-mediated cell death is strongly dependent on the existence of functional p53 in HCT 116 cells. Further, we provide the evidence that etoposide can induce the cytochrome c release from isolated mitochondria, and etoposide-induced cytochrome c release is not accompanied with the large amplitude swelling of mitochondria. These data suggest that etoposide can directly induce the mitochondrial dysfunction irrespective of p53 status, and it may, at least in part, account for the p53-independent pathway in cell death induced by chemotherapeutic agents.

• Korean Journal of Clinical Pharmacy
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• v.19 no.1
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• pp.32-36
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• 2009

The aim of this study was to investigate the effect of simvastatin on the pharmacokinetics of nicardipine in rats. Pharmacokinetic parameters of nicardipine were determined after an oral administration of nicardipine (12 mg/kg) to rats coadministered with simvastatin (0.3 and 1.0 mg/kg). Compared with the control (given nicardipine alone), coadministration of simvastatin (1.0 mg/kg) significantly (p<0.05) increased the area under the plasma concentration (AUC) and peak plasma concentration ($C_{max}$) of nicardipine. The relative bioavailability (RB%) of nicardipine increased from 1.19- to 1.48-fold. However there were no significant changes in $t_{max}$, and $t_{1/2}$ of nicardipine. The enhanced oral bioavailability of nicardipine might be due to an inbition of cytochrom P450 3A mediated-metabolism of nicardipine in the intestine and in the liver by simvastatin. Based on these results, the concurrent use of simvastatin significantly enhanced the oral exposure of nicardipine in rats. The dosage regimen of nicardipine should be taken into consideration for potential drug interaction when combined with simvastatin in clinics.

• Journal of the Korean Society of Radiology
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• v.8 no.6
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• pp.325-332
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• 2014

Metallic nanoparticles have attractive properties in biomedical applications such as diagnostics and therapeutics. Cross linked dextran coated iron oxide nanoparticles (SPIONs) and silica coated gadolinium oxide nanoparticles (SPGONs) have been synthesized as a radiosensitizer in the proton beam cancer therapy. The dextran and silicaused for the protective moieties on the SPIONs and SPGONs respectively. Size distributions of synthesized nanoparticles were confirmed 3~5 nm for SPIONs and 30~100 nm for SPGONs by transmission electron microscope (TEM). Cell survival fraction measurement and Western blot assay were performed to evaluate the radiosensitization effects of synthesized radiosensitizer. The calculated radiosensitization of SPIONs and SPGONs at 90 % cell death from the measured cell survival curves were 1.23 and 1.03 respectively. Western blotting results also show the same consistent results that the amount of released cytochrome c from mitochondria was considerably increased for the cancer cells taken up SPIONs.

• Applied Microscopy
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• v.38 no.2
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• pp.125-133
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• 2008

Cytochrome-c-oxidase in mitochondria membrane is one of the most important factors for energy generation in the cell. As well as it is electron transfer enzyme, it is also heavily related to the apoptosis and other pathologic conditions. Meanwhile, porin is a protein located in inner and outer membranes of mitochondria, which is assumed to be functionally correlated with cytochrome-c-oxidase. It functions as forming electron transfer chain and conveying ATP. Therefore, using the immune-microscopy, It compared the distribution of cytochrome-c-oxidase and porin to figure out the formation and changes on cytochrome-c-oxidase in mitochondrial cristae. The sarcroplasm of cardic muscle tissue has many mitochondria. They are classified into two groups: the mitochondria with many cytochrome-c-oxidase and the mitochondria with only porins. The mitochondria with porins had few cytochrome-c-oxidases in their membrane; in contrast, the other mitochondria with rich cytochrome-c-oxidase had few porins in their walls. In addition, according to the location of the tissue in bovine heart, distribution of those kind of mitochondria had been clearly separated. As a result, it could be assumed that immature mitochondria has many porins to transfer the protein materials from sarcroplasm through the porins, and they made cytochrome-c-oxidase until it is enough, and then they decreased the porin and maintained minimum number of the porin.

• Applied Biological Chemistry
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• v.27 no.3
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• pp.174-179
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• 1984

Some physico-chemical properties of proteolytic enzyme produced from Streptomyces alboniger Hesseltine were characterized. The optimal pH and temperature of the enzyme were around pH 9.0 and $40^{\circ}C$, respectively. The enzyme was stable between pH $6.0{\sim}10.8$ and the enzyme activity was not inactivated by heat treatment in lower temperature than $40^{\circ}C$. However the enzyme activity decreased by 70% of the initial activity for 10minutes at $70^{\circ}C$. The Km value was $7.1{\mu}M$ with Hammarsten casein and $333.3{\mu}M$ with cytochrom C. The activity of enzyme was inhibited by metal ions in the order of $Fe^{+++}>Hg^{++}>Cu^{++}>Pb^{++}>Zn^{++}$, whereas $Ca^{++}$ increased the enzyme activity. There was no effect of $Mg^{++}$ and $Co^{++}$ on the enzyme activity. The enzyme was inhibited by EDTA strongly. When $Ca^{++}$ was added to the EDTA-denaturated enzyme, the activity of enzyme was restored.

• Journal of Pharmaceutical Investigation
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• v.37 no.2
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• pp.107-111
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• 2007

Epigallocatechin gallate (EGCC), a flavonoid, is the main component of green tea extracts. EGCG has been reported to be an inhibitor of P-glycoprotein (P-gp) and cytochrom P450 3A(CYP3A4). This study investigated the effect of long-term administration of EGCG on the pharmacokinetics of verapamil in rats. Pharmacokinetic parameters of verapamil were determined after oral administration of verapamil (9 mg/kg) in rats pretreated with EGCG (7.5 mg/hg) for 3 and 9 days. Compared to oral control group, the presence of EGCG significantly (p<0.01) increased the area under the plasma concentration-time curve (AUC) of verapamil by 102% (coad), 83.2% (3 days) and 52.3% (9 days), and the peak concentration $(C_{max})$ by 134% (coad), 120% (3 days) and 66.1% (9 days). The absolute bioavailability (A.B.%) of verapamil was significantly (p<0.01) higher by 8.4% (coad), 7.7% (3 days), 6.4% (9 days) compared to control (4.2%), and presence of EGCG was no significant change in the terminal half-life $(t_{1/2})$ and the time to reach the peak concentration $(T_{max})$ of verapamil. Our results indicate that EGCG significantly enhanced oral bioavailability of verapamil in rats, implying that presence of EGCG could be effective to inhibit the CYP3A4-mediated metabolism and P-gp efflux of verapamil in the intestine. Drug interactions should be considered in the clinical setting when verapamil is coadministrated with EGCG or EGCG-containing dietary.

• Environmental Mutagens and Carcinogens
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• v.26 no.3
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• pp.77-85
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• 2006

2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin(TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although TCDD is recognized as potent carcinogens, relatively little is known about their role in the tumor promotion and carcinogenesis. It is known that TCDD can increase of cancer risk from various types of tissue by a mechanism possibly involving the aryl hydrocarbon receptor (AhR) activation. In this study, effects of TCDD on cellular proliferation of normal human skin and lung fibroblasts, Detroit551 and WI38 cells were investigated. In addition, to enhance our understanding of TCDD-mediated carcinogenesis, we have investigated process in which expression of Erk1/2, cyclinD1, oncogene such as Ha-ras and c-myc, and their cognate signaling pathway. TCDD that are potent activators of AhR-mediated activity was found to induce significant increase of cytochrome P4501A1 mRNA expression, suggesting a presence of functional AhR. These results support that CYP1A1 enzyme may be involved in the generation of TCDD-induced toxicity. Moreover mitogen-activated protein kinases (MARKs) phosphorylation and cyclin D1 overexpression are induced by TCDD, which corresponded with the progression of cellular proliferation. However, TCDD did not affected Ha-ras and c-myc mRNA expression. Taken together, it seems that TCDD are could be a part of cellular proliferation in non-tumorigenic normal human cells such as Detroit551 and WI38 cells through the upregulation of MAPKs signaling pathway regulating growth of cell population. Therefore, AhR-activating TCDD could potentially contribute to tumor promotion and Detroit551 and WI38 cells have been used as a detection system of tumorigenic effects of TCDD.

• Toxicological Research
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• v.14 no.3
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• pp.293-300
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• 1998

Previous studies have shown that the heterocycles including thiazoles are efficacious in inducing phase phase II metabolizing enzyme as well as certain cytochrome P450s and that the inductin of these matabolizing enzymes by the heterocyclic agents is highly associated with their hepatotoxicity. In the present study, the effects of benzylisothiazole (BIT), which has a isothiazole moiety, on the expression of microsomal epoxide hydrolase (mEH), major glutathione S-transerases and cytochrome P450s were studied in the rat liver in association with its hepatotoxicity. Treatment of rats with BIT(1.17 mmol/kg, 1~3d) resulted in substantial increases in the mEH. rGSTA2, rGSTA2, rGSTM1 and rGSTM2 mRNA levels, whereas rGSTA3 and rGSTA5 mRNA levels were increased to much lesser extents. A time-course study showed that the mRNA levels of mEH and rGSTs were greater at 24hr after treatment than those after 3 days of consecutive treatment. Relative changes in mEH and rGST mRNA levels were consistent with those in the proteins, as assessed by Western immunoblot analysis. Hepatic cytochrom P450 levels were monitored after BIT treatment under the assumption that metabolic activation of BIT may affect expression of the enzymes in conjunction with hepatotoxicity. Immunoblot analysis revealed that cytochrome P450 2B1/2 were 3-to 4-fold induced in rats teatd with BIT(1.17 mmol/kg/day.3days), whereas P450 1A2, 2C11 and 3A1/2 levels were decreased to 20~30% of those in unteatd rats. P450 2E1 was only slightly decreased by BIT. Thus, the levels of several cytochrome P450s were suppressed by BIT treatment. Rats treated with BIT at the dose of 1.17mmol/kg for 3 days exhibited extensive multifocal nodular necrosis with moderate to extensive diffuse liver cell degeneration. No notable toxicity was observed in the kidney. These results showed that BIT induces mEH and rGSTs in the liver with increases in the mRNA levels, whereas the agent significantly decreased major cytochrome P450s. The changes in the detoxifying enzymes might be associated with the necrotic liver after consecutive treatment.