• Archives of Pharmacal Research
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• 제23권1호
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• pp.22-25
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• 2000

Formation of glutathione (GSH) conjugates with 2- or 6-(1-hydroxymethyl)- and 2-(1-hydroxyethyl)-DMNQ derivatives (DMNQ, 5,8-dimethoxy-1,4-naphthoquone was carried out in phosphate buffer (pH 7.4), in the presence of glutathione-S-transferase (GST), in rat liver S-9 fraction and by perfusion, and the rates of conjugates formation were compared and correlated to cytotoxicity. The GSH conjugates of 6-(1-hydroxyalkyl)-DMNQ derivatives were formed faster than 2-(1-hydroxyalkyl)-DMNQ derivatives under all of the media, implying that steric hindrance was the cause of lowering the rate of conjugate formation of 2-substituted derivatives. For both isomers, addition of GST did not improve the reaction rate, compared with that in buffer, while the reaction in the S-9 fraction and the perfusate was accelerated to a great extent. The catalytic effect of the S-9 fraction and the perfusate contain an effective system relaxing the steric hindrance of 2-(1-hydroxyalkyl)-DMNQ derivatives. Furthermore, a good correlation between the formation of the GSH conjugates and the cytotoxic activity of both naphthazarin isomers suggests that the steric hindrance is a cause of lowering the cytotoxicity of 2-isomers.

• Archives of Pharmacal Research
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• 제19권6호
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• pp.514-519
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• 1996

In order to understand the mechanism of action of flavonoids on the drug metabolizing enzyme, cytochrome P450IA1, this study was undertaken to examine the effect of chrysin, morin, myricetin and aminopyrine on the activities of ethoxyresorufin O-deethylase and benzo(.alpha.) pyrene hydroxylase in the liver. In the isolated perfused rat liver that was pretreated with 3-methylcholanthrene (3MC), chrysin, morin, myricetin and aminopyrine inhibited the activity of ethoxyresorufin O-deethylase with concentration dependent manner. The isolated liver perfusion with chrysin, morin, myricetin and aminopyrine showed inhibition on the induction of ethoxyresorufin O- deethylase by 3MC. And also, in mouse liver hepa I cells, 3MC-stimulated the benzo(.alpha.)pyrene hydroxylase activity which was inhibited by chrysin, morin, myricetin and aminopyrine. These results strongly suggested that hydoxylated flavonoids interfered not only the induction of cytochrome P45OIA1 enzymes by 3MC but also the interaction of substrates and enzyme.

• Radiation Oncology Journal
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• 제22권4호
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• pp.288-297
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• 2004

목적: 종양 내에서 산소공급 부족현상으로 발생하는 저산소증 조직에서 저온온열치료($42^{circ}C$)와 nicotinamide에 의한 perfusion limited 저산소증의 개선 효과를 마우스 종양 모델을 이용하여 종양 내 $[^18F]FMISO$ 섭취변화를 이용하여 증명할 수 있는지 알아보고자 하였다. 대상 및 방법: C3H 마우스에 $[^18F]FMISO$를 정주하고 11개 장기에서 $\%ID/g$을 구하여 biodistribution을 관찰하였다. 또한 같은 마우스에 동종 종양세포인 SCC7을 이식하여 종양모델을 만들고 저온온열치료($42^{circ}C$)와 nico-tinamide를 투여한 마우스와 대조군 마우스에서 $[^18F]FMISO$의 섭취정도 차이를 $\%ID/g$, autoradiography, PET scan을 시행하여 비교하고자 하였다. 결과: 대조군에서 종양의 FMISO의 섭취는 5.1+/-2.28 $\%ID/g$였고, 종양/근육, 종양/혈액의 섭취비는 2.2와 1.8이었다. 실험군에서는 각각 2.4+/-0.64 $\%ID/g$, 1.4와 1.2를 나타내어 대조군보다 유의하게 낮았다(p<0.021). Autoradiography에서 대조군의 종양 내부에 FMISO가 섭취됨을 확인하였고, 저온온열치료와 nico-tinamide를 투여한 실험군에서는 섭취가 감소된 것을 관찰하였다. 결론: C3H 마우스와 동종 종양세포인 SCC-VII을 이용한 종양모델에서 $[^18F]FMISO$가 종양내에 섭취가 되어 자산소증 종양모델로 적절함을 확인하였고, 저온온열치료($42^{circ}C$)와 nicotinamide에 의한 perfusion limited 저산소증 개선효과를 $[^18F]FMISO$의 종양 내 섭취가 감소하는 것을 통하여 확인할 수 있었다.

• Applied Microscopy
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• 제23권2호
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• pp.53-77
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• 1993

In this study, an attempt was made to investigate the probable organelles participating in the secretion of biligrafin. The animals (ICR male mice, 25-30gm) were divided into normal control and 6 biligrafin injected groups to which 30% biligrafin (0.006ml/gm b.w.) were injected at 10, 20, 40, 80, 160 and 320 min prior to the sampling. The mice of each group were perfused through the heart with ice-cold 2.5% glutaraldehyde buffered with 0.1M Na-cacodylate (pH. 7.4) under the Na-pentobarbital (Nembtal 0.0015mg/gm b.w.) anesthesia and liver tissues were taken from each group. Some specimens were immersed 1 hr in the same solution used in the perfusion. After an overnight rinse in 0.1M Na-cacodylate buffer containing 10% DMSO and 7.6% sucrose, $75{\mu}m$ fronzen sections were made for cytochemical study. The sections were incubated in thiamin pyrophosphatase (TPPase) and inosine diphosphatase (ID Pase) media for 70 min at $37^{\circ}C$ respectively and acid phosphatase (AcPase) medium for 40 min at $37^{\circ}C$. They were postfixed in 1 % $OsO_4$ for 1 hr. The other specimens were immersed for 8 hrs in the fixative consisting of 2.5% glutaraldehyde and 3.0% paraformaldehyde buffered with Na-cacodylate (pH. 7.4). All of the osmificated specimens were processed for electron microscopy. In both normal and biligrafin injected groups, endoplasmic reticulum (ER), vacuoles, Golgi apparatus and lysosomes were seen in the vicinity of bile canaliculus. In the biligrafin injected groups, however, the Golgi apparatus appeared to be decreased and ER and vacuoles were dilated and increased. The rough endoplasmic reticulum (RER) having a few attached ribosomes appeared to be the round saccule, especially at 20 min after biligrafin injection. Smooth endoplasmic reticulum (SER) seemed to be formed by the detachment of ribosomes at the cisternal end of RER. The cistern of SER showed saccules which probably budded off to form the vacuole. The vacuoles were devoid of visible centents. This finding seemed to be in agreement with the biochemical property of the bile constituents. The fusion between the vacuoles and bile canaliculus were frequently seen in the groups injected with biligrafin. The lysosome did not show any changes in the biligrafin injected groups. Accumulation of some material and lipid droplets were seen at the 40 and 80 min after biligrafin injection, especially at the latter. At 160 and 320 min after biligrafin injections, however, they were decreased successively while the RER stack, free ribosomes and polysomes were increased. Although the reactive products of TPPase and IDPase were observed in the ER saccules and vesicles of the normal control and biligrafin injected groups, the fusion between the bile canaliculus and saccules or vesicles could easily be seen in the latter. The AcPase activity, however, was observed in the cistern at the maturing face of Golgi apparatus and lysosomes in both normal and biligrafin groups. The results suggest that the biligrafin is excreted via the vesicles, vacuoles or sacoules probably derived from the SER without the participation of Golgi apparatus and lysosomes, and the excess amount of material is stored as inclusions during the repairing of the organelles being overactive.