• Journal of Nutrition and Health
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• v.23 no.1
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• pp.11-18
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• 1990

Sprague-Dawley male rats were fed the diet of p/s 4.0(soybean oil : I), p/s 0.08(Beef tallow : II) at the level of 15% fat until 8 weeks after weaning. I & II groups were divided into 4 sub-groups by diets with or without 0.3% butylated hydroxytoluene(BHT). 2-AAF was injected at the age of $5_{1/2}$, 6, $5_{1/2}$, 7 weeks. MFO system enzyme(cytochrome p-450, cytochrome p-450 reductase, cytochrome b5) activities and lipid peroxide were determined from isolated liver microsome. 2-AAF injected young rats had growth retardatiion. Lipid peroxide values were not influenced greatly by dietary fat, 2-AAF and BHT. Cytochrome p-450 contents were increased in I-BHT-AAF & II-AAF groups by 2-AAF and its contents were not affected by BHT. But cytochrome p-450 and cytochrome p-450 reductase were not increased in soybean oil diet ybean oil groups. Cytochrome b5 was not influenced by dietary fat, 2-AAF and BHT. Cytochrome p-450 and lipid peroxide, cytochrome p-450 reductase and cytochrome b5, which transfer to MFO system, appeared to have positive correlations(r=0.2474, r=0.2475, p<0.05) each other. This result suggests that MFO system metabolizing 2-AAF was influenced by dietary fats and BHT. 2-AAF induced growth retardation in young rats.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.312.3-313
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• 2002

Recently we have reported that various hydroxystilbenes show strong inhibition of human P450 1 activity. A series of synthetic trans-stilbene derivatives were prepared and their inhibitory potentials were evaluated with the bacterial membrane of recombinant human P450 1A1, 1A2 or 1B1 coexpressed with human NADPH-P450 reductase to find new candidates for cancer chemoprevention, Of the compounds tested. SY-021 (3.5-dimethoxyphenyl vinyl thiophene) exhibited a potent inhibition of human P450 181 with an IC$_{50}$ value of 2 nM. SY-021 also showed the inhibitrion of P450 1A1 with IC$_{50}$ value of 61 nM and P450 1A2 with IC$_{50}$ value of 11 nM. SY-021 showed 31-fold selectivity for P450 1B1 over P450 1A1 and 6-fold selectivity for P450 1B1 over 1A2. We have further investigated the inhibition kinetics of P450 1A1. 1A2 and 1B1 by SY-021. The modes of inhibition by SY-021were non-compeitive for all three P450 1 enzymes. Effect of preincubation with NADPH on inhibition of P450 1B1 by SY-021 was determined. These results suggest that SY-021 is one of the mostj potent inhibitor of human P450 1 enzymes and may be considered as a good candidate for a cancer chemopreventive agent in human

• Biomedical Science Letters
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• v.1 no.1
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• pp.89-94
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• 1995

Considering the planar structure and nonpolar properity of benzo(a)pyrene(B(a)p) and the planar heme part of cytochrome P-450, stacking interaction is probable. MO calculation on B(a)P and heme part of cytochrome P-450 were carried out to dertermine probable stacking interaction models. In this case, orbital interaction is most important. Accordingly, the stacking positions have high eigen vector in frontier orbital and boning type between two molecules. In this way, five probate models were selected and examined by MN2 and MO method. The most probable .stacking interaction model which is the 4, 5, 6 positions of B(a)P overlap carbon atom and pyrrole ring of ring of heme group was determined.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.6
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• pp.859-866
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• 1995

This study was done to investigate the effects of chronic ethanol feeding on hepatic microsomal cytochrome system, lipid peroxidation and peroxide metabolizing enzyme activities in 2-acetylaminofluorene(2-AAF) treated rats. Male Sprague-Dawley rats, weighing 120~125g, were pair-fed liquid diets containing 35% of total calories either as ethanol or isocaloric carbohydrates for 6 weeks. After 4 weeks of experimental diet feeding, 2-AAF(100mg/kg body weight) was injected twice a week intraperitoneally. Both weight and percent liver weight per body weight were significantly changed by ethanol feeding. Hepatic microsomal lipid peroxide value and the activities of glutathione(GSH) peroxidase and GSH reductase were not changed by either ethanol or 2-AAF treatment. However the analysis of cytochrome systems showed that both ethanol and 2-AAF increased cytochrome P-450 and bs contents although cytochrome P-450 content was moe affected by 2-AAF while cytochrome b5 content by ethanol. Cytosolic GSH S-transferase activity, which is often elevated during chemical carcinogenesis, also significantly increased by either ethanol feeding or 2-AAF treatment. Overall values for the cytochrome contents and GSH S-transferase activities were highest in 2-AAF treated rats fed ethanol. These results might support the hypothesis that the increase in liver cancer risk associated with chronic ethanol consumption might be due to, at least in part, enhancement of carcinogen bioactivation by ethanol.

• Animal cells and systems
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• v.13 no.4
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• pp.439-445
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• 2009

Cytochrome P450 aromatase (P450arom) catalyzes the conversion of androgens to estrogens and plays an important role in reproduction and development in vertebrates. We investigated the expression patterns of ovarian P450arom (P450aromA) and brain P450arom (P450aromB) mRNA during sex change in black porgy. Maturity was divided into seven stages from male to female (immature testis, mature testis, testicular portion of mostly testis, ovarian portion of mostly testis, testicular portion of mostly ovary, ovarian portion of mostly ovary, and mature ovary). P450aromA expression was significantly higher in the ovarian portion of mostly-ovarian stage fish, and P450aromB expression was highest in the brain of black porgy with mostly-ovarian gonads. Histology showed that testicular tissues were disintegrated with the development of ovarian tissue associated with an increase in the expression of the two P450arom mRNAs during sex change. Interestingly, among various tissues, P450aromA was only expressed in the ovary, and P450aromB was only expressed in the brain. To understand the role of gonadotropin-releasing hormone (GnRH) and estradiol ($E_2$), we injected exogenous hormone (GnRH analogue [GnRHa] and $E_2$) into immature black porgy. In the GnRHa group, expression of the two P450arom genes decreased 12 h after injection, and expression of the two P450arom genes were significantly higher at 6 dafter $E_2$ injection. These results provide useful baseline knowledge on the mechanism of natural sex change in black porgy.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.148.2-149
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• 2003

Recently we have reported that various hydroxystilbenes show strong inhibition of human cytochrome P450 1 enzyme activities. A series of syntheic trans-stilbene derivatives were prepared and their inhibitory potentials were evaluated with the bacterial membrane of recombinant human cytochrome P450 1A1, 1A2 and 1B1 coexpressed with hyman NADPH-P450 reductase to find a new inhibitor of cytochrome P450 enzymes. Of the compounds tested, SY-081 exhibited a potent inhibition of human cytochrome P450 1B1 with an $IC_50$ value of 2.6 nM. (omitted)

• Applied Biological Chemistry
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• v.38 no.2
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• pp.168-173
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• 1995

To investigate the effects of endosulfan on cytochrome P-450 enzymes in mouse(Balb c.), endosulfan was given by an intraperitoneal dose of 7.5 mg/kg. The treatment of endosulfan increased the cytochrome P-450 content by 3.3 to 4.2 fold, cytochrome $b_5$ content by 2.3 to 3.8 fold, NADPH cytochrome P-450 reductase activity by 5.3 to 6.4 fold and total haem content by 3.1 to 3.6 fold of mouse liver after 48 hrs of intraperitoneal injection. Endosulfan cytochrome P-450 absorption spectrum exhibited miximum at 387 nm and 389 nm and broad near 407 nm in the liver microsome. Reduced P-450-CO spectrum of the liver microsome exposed by the treatment of endosulfan showed maximum at 449 nm and 450 nm compared to that of the control having maximum at 451 nm, which indicated endosulfan induced cytochrome P-450 new isozymes. Aldrin epoxidase activities in the mouse liver and kidney were increased by 2.8 and 2.1 fold by the treatment of endosulfan. Also 7-ethoxyresorufin dealkylase activities in the mouse liver and kidney were elevated by 1.7 and 1.8 fold by treatment of endosulfan.

• Korean Journal of Weed Science
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• v.17 no.1
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• pp.59-65
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• 1997

Bentazon 6-hydroxylase (B6H) and cinnamic acid 4-hydroxylase (CA4H) activities were determined in rice (Oryza sativa L.) microsomes to study methods of enhancing cytochrome P-450 mediated aryl hydroxylation of bentazon by hydoxylase inducing compounds. Pretreating rice seeds with 1,8-naphthalic anhydride at 0.5-2% and fenclorim at 5 and 10 ${\mu}M$ increased B6H and CA4H activities. Treatments of rice seedling with ethanol 2.5% enhanced B6H and CA4H activities, and with phenobarbital at 12 mM enhanced B6H activity, and CA4H activity was enhanced at 2 mM. B6H activity was synergistically enhanced by combined treatments of ethanol 2.5 or 5% and phenobarbital 8 or 12mM and also that of 1,8-naphthalic anhydride 0.5 or 1% and phenobarbital 8 or 12 mM, but CA4H activity was decreased by combined treatment. Five-day-old rice seedlings showed higher B6H and CA4H activities which decreased with seedling age.

• BMB Reports
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• v.30 no.1
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• pp.73-79
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• 1997

This study was designed to investigate the effects of dietary garlic powder on cytochrome P450 enzymes and membrane stability in murine hepatocarcinogenesis initiated by diethylnitrosamine (DEN). Male Sprague-Dawley rats received a single intraperitoneal injection of DEN (200 mg/kg body wt) dissolved in saline. After 2 weeks on a basal diet, animals were fed diets containing 0. 0.5. 2.0. or 5.0% garlic powder for 6 weeks, and were subjected to two-thirds partial hepatectomy. The areas of placental glutathione S-transferase (GST-P) positive foci were inhibited in rats fed with garlic diets. GST-P is the most effective marker for DEN-initiated lesions. Hepatic microsomal lipid peroxidation was significantly decreased in rats fed with 2.0 and 5.0% garlic powder diets compared with that observed in the control animals and hepatic microsomal glucose 6-phosphatase (G6Pase) activity was found to increase significantly in rats fed 0.5 and 2.0% garlic powder diets. Thus as little as 0.5% garlic powder has a positive effect on the stability of hepatic microsomal membranes. p-Nitrophenol hydroxylase (PNPH) activity and the level of cytochrome P450 2E1 protein in the hepatic microsomes from rats fed diets containing 2.0 and 5.0% garlic powder were much lower than those of control microsomes. Rats fed 5.0% garlic powder diets exhibited the lowest P450 2E1 activity and protein levels among groups. Pentoxyresorufin O-dealkylase activity and immunoblot (cytochrome P450 2B1) analyses were not different between groups. However, the levels of cytochrome P450 1A1/2 protein in rats fed 0.5 and 2.0% garlic powder were significantly induced compared to controls. These results suggest that 2.0% garlic powder is effective in inhibiting the areas of GST-P positive foci, modulating certain isoforms of cytochrome P450 enzymes and stabilizing the hepatic microsomal membrane. Thus, the selective modification of cytochrome P450 enzymes and membrane stability by dietary garlic powder may influence areas of GST-P positive foci and chemoprevention of post-initiation of rat hepatocarcinogenesis.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.128-128
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• 1995

To investigate the mechanism of the regulation of cytochrome P450IA1 gene expression, ethoxyresorufin deethylase(EROD) and benzo(a)pyrene hydroxylase in B6 mouse liver, in isolated perfused rat liver system. and in B6 mouse hepatocyte Hepa-I cells were examined. In C57BL/6N mouse, 3-methylcholan- throne( 3MC ) treatment have resulted in the stimulation of EROD activity based on fluorometry by 2.79 fold comparirng with that of control. Measurement of mRNA of cytochrome P450 was carried out by either nothern blot or dot blot analysis. Findings are similar to that of studies with enzymes. Furhtermore, when RTPCR method was applied to detect mRNA in Hepa I cell and liver tissues the results were more clear. Cytochrome P450IA1 upstream DNA containing CAT construct was transfected into Hepa-1 cells. After transfection of CAT construct, 3MC and flavonoids, such as, chrysin, hesperetin, kaempferol, morin, myricetin and aminoyrine were treated. 48 Hours after treatments, cells were harvested and assayed for CAT mRNA by RTPCR. 3MC treatment to hepa I cells transfected with trout P450IA1-CAT construct increased CAT mRNA by 2.81 fold when it was compared with that of control. This increase CAT mRNA was decreased by concomitantly treated flavonoids and aminopyrine. The level of CAT protein was 29.2-58.0% of 3MC stimulated CAT protein. Results of this study suggested that RTPCR seems to be a very good method to study regulation of gene expression in liver tissue or Hepa cells.