• Journal of Nutrition and Health
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• 제23권1호
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• pp.11-18
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• 1990

Sprague-dawley 숫쥐를 식이지방을 달리하여(I:Soybean oil p/s 4.0, II:beef tallow p/s 0.08) 이유후 8주동안 사육하였다. 이때 I,II군은 각각 기초식이군, 기초식이군에 0.3% butylated hydroxytoluene(BHT)를 첨가신킨 군, 생후 5~7주 사이에 4번의 2-Acetylaminofluorene(2-AAF)를 투여한 군 2-AAF를 투여하고 BHT도 먹인 군으로 나누었다. BHT는 이유 후부터 식이에 섞어 먹였으며 2-AAF를 투여하지 않은 군읜 2-AAF 주사에 의해 얻는 stress와 같은 효과를 주기위해 placebo로 polyethylene glycol 300을 투여하였다. Mixed function oxidase(MFO)계의 효소인 cytochrome p-450, cytochrome b$_5$및 cytochrome p-450 reductase와 과산화지질 등을 측정하였다. 성장기에 2-AAF의 투여는 성장지연을 초래하였으며 지질과산화물은 지방의종류, 2-AAF,BHT 등에 의해 큰 차는 없었다. Cytochrome p-450은 2-AAF에 의해 I-BHT-AAF와 II-AAF군에서 증가되었고 BHT에 의해서는 차이가 나지 않았다. 불포화지방을 먹인경우 cytochrome p-450과 cytochrome p-450 reductase가 2-AAF에 의해 증가되기보다는 오히려 감소하거나 I,II군에 비해 별 차이가 없었는데 2-AAF의 농도와 식이의 불포화도가 높아 세포막이 손상되었기 때문이라 사료된다. Cytochrome $b_5$는 각군 사이에 별 차가 없었다. Cytochrome p-450과 과산화지질(r=0.2475, p<0.05), cytochrome p-450 reductase와 cytochrome $b_5$ (r=0.2475, P<0.05)가 각각 양의 상관관계를 나타내었다. 따라서 2-AAF를 대사시키는 MFO계는 식이지방의 종류 및 BHT의 존재에 따라 영향을 받고, 특히 불포화지방식이인 경우 2-AAF를 대사시킬 수 있는 cytochrome p-450 유도 및 합성능력이 매우 저조함을 알 수 있으며 2-AAF는 어린 쥐의 성장을 지연시켰다.

• Toxicological Research
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• 제7권2호
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• pp.239-255
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• 1991

Several types of IFNs were tested for their ability to suppress TCDD-inducible P-450 dependent mixed function oxidase (MFO) system in mouse primary hepatocytes. Mouse IFN-gamma (IFN-G) markedly suppressed EROD activity when added at the same time as TCDD (10 nM). The antagonism of EROD activity by IFN-G exhibited both a dose-(10-100 U/ml) and time-depedence. In contrast, mouse IFN-A/B was only moderately suppressive and only at high concentrations (500 U/ml). Rat IFN-G was even more selective than mouse, wherase human IFN-G had no activity.

• 한국식품영양과학회지
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• 제25권1호
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• pp.21-26
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• 1996

본 연구는 streptozotocin 유발 당뇨쥐에서의 MFO계활성 변화 및 이에 지질과산화를 관찰하고자 체중이 140kg 내외의 Sprague-Dawley 종 흰쥐 숫컷을 대조군과 당뇨 유발 시험군으로 나누어 4주간 사육하였다. 당뇨군은 STZ로 당뇨를 유발시켰으며 당뇨 유발 6일후 쥐를 희생기켜 간조직 및 폐조직 microsome 중의 cytochrome $P_{450}$ 및 cytochrome $b_[5}$ 함량과 NADPH-cytochrome $P_{450}$ reductase 활성도를 측정하고 아울러 microsome내의 지질과산화물을 측정하여 다음과 같은 결과를 얻었다. 실험군간에 식이 섭취량은 차이가 없었으나, 체중 증가량과 식이 효율은 당뇨군이 STZ군에 비해 현저하게 감소하였다. 간장 및 폐조직의 무게는 대조군과 당뇨군간에 유의적인 차이는 없었다. 간조직 및 GP조직 중의 cytochrome $P_{450}$ 함량은 대조군에 비해 당뇨군이 150%, 175%씩 증가하였다. 간조직 및 폐조직 중의 cytochrome $b_{5}$은 대조군에 비해 당뇨군이 53%,116%씩 각각 증가하였다. 간조직에서의 NADPH-cytochrome $P_{450}$ reductase 활성은 당뇨군이 대조군에 비해 46% 증가하였으며, 폐조직에서는 75%증가하였다. 지질과산화물가는 당뇨군이 대조군에 비해 간족에서는 약 95% 높았으며 폐조직에서는 73%높았다. 이상의 결과에서 STZ 유발 당뇨쥐에서는 MFO system의 활성도가 대조군에 비해 현저하게 증가되고 지질과산화반응이 같으 srudgid이 촉진되었으며 폐조직에서도 간조직에서와 비슷한 경향이었다. 이러한 것은 당뇨군에서는 MFO system의 활성증가로 free radical 생성이 증가되고 그 결과 지질과산화가 촉진되었다고 볼 수 있다.

• Toxicological Research
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• 제8권2호
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• pp.265-272
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• 1992

Effects of repeated physical exercise on the carbon tetrachloride ($CCl_4$) hepatotoxicity were examined in adult female rats. Rats were introduced into a cylindrical rotating cage and forced to exercise for 1 hr each day, 6days/week, for 5 consecutive weeks at a speed starting from 10m/min, increased by 1m/min per day until the speed reached 27m/min. Significantly less body weight gain was observed in the exercise group suggesting that physical fitness had been induced in these animals. Eighteen hours following termination of the last exercise bout rats were treated with $CCl_4$(2 mmol/kg.ip). The $CCl_4$-induced heptotoxicity was significantly potentiated in the repeated exercise group compared to the resting sedentary animals as determined by changes in serum sorbitol dehydrogenase (SDH), glutamic oxaloacetic transaminase(GOT), glutamic pyruvic transaminase (GPT), and glucose-6-phosphatase(G-6-Pase) activities when measured 24hrs following the $CCl_4$ treatment. Hepatic drug metabolizing activity was determined in order to elucidate the underlying mechanism of potentiating action of the $CCl_4$ hepatotoxicity induced by repeated physical exercise. Repeated exercise increased the hepatic microsomal cytochrome P-450 contents and aminopyrine N-demethylase activity. The results suggest that the potentiation of $CCl_4$ hepatotoxicity by repeated exercise is associated with induction of the mixed function oxidase (MFO) enzyme system mediating the metabolism of $CCl_4$ to its active metabolite(s).

• Toxicological Research
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• 제11권1호
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• pp.31-36
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• 1995

Cyclophosphamide (CP) must be enzymatically activated by cytochrome P450(CYP)-linked mixed-function oxidation pathway to be either mutagenic or teratogenic. Influences of alterations in hepatic mixed-function oxidase acitivity and glutathione (GSH) content on the embryotoxicity of CP were studied in rat whole embryo culture system. The embryotoxicity of CP was compared using rat S-9 fraction (S-9) pretreated with chemicals inducing different CYP isozymes, acetone (ACE), Aroclor 1254 (ARO), $\beta$-naphthoflavone (NAF) and phenobarbital (PHE). When 10.5 day embryos were cultured in the immediately centrifuged rat serum for 48 hrs using general gas char{ging schedule, CP$(40{\mu}g/ml)$ with S-9 induced by either NAF or PHE increased the incidence of realformations and significantly decreased embryonic growth compared with the non-induced S-9 group. ACE or ARO induced S-9 group showed no significant difference in embryonic growth. These data suggest that PB and/or NAF inducible CYP isoenzymes are mainly involved in the activation of CP. To examine the effect of GSH on the embryotoxicity of CP, 10.5 day embryos were exposed to CP and S-9 after preincubation with 10 mM of GSH for 3 hrs. In the GSH pretreated group the growth of embryos increased significantly compared with that of the untreated group, suggesting that GSH may protect embryos in culture from some toxic effects of CP.

• 한국식품영양과학회지
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• 제20권3호
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• pp.203-208
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• 1991

The present study was undertaken in order to elucidate the effects of pretreatment with nicotinamide on changes in the hepatic metabolizing enzyme system inducted by streptozotocin (STZ). In rats, STZ(50mg/kg) administered by tail vein caused a significant rise in hepatic aniline hydroxylase and a decrease in aminopyrine N-demethylase when compared to control (p<0.05). Pretreatment with nicotinamice inhibited these effects (p<0.05). Similarly, STZ induced changes in hepatic microsomal cytochrome P-450 activity were inhibited by pretreatment with nicotinamide (p<0.05). However, changes in UDP-glucuronyl transferase and sulfortransferase activity were not significantly different(p>0.05). Pretreatment with nicotinamide also prevented STZ induced increases in glutathion S-tranferase activity when compared to the control(p<0.05). There results suggest that nicotinamide pretreatment suppresses STZ-induced changes in the hepatic metabolizing enzyme system.

• 생약학회지
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• 제23권2호
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• pp.81-88
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• 1992

The effects of scoparone, one of coumarin derivative on the hepatic bromobenzene metabolizing enzyme system was estimated in rats. Scoparone pretreatment revealed dose-dependently the recovery of decrease in epoxide hydrolase activity due to the bromobenzene(310 mg/kg, i.p.) treatment. And also scoparone and scopoletin (each 5mg/kg, p.o.) pretreatments showed two times increase in the $V_{max}$ values compared to those of bromobenzene-treated group which were calculated from tripartite reciprocal plots. The mode of protective effect of scoparone against bromobenzene induced toxicity is considered to be due to the induction of microsomal enzyme activity by scopoletin, the intermediate metabolite of scoparone. The changes in cytochrome P-450 activity, aminopyrine N-demethylation, aniline hydroxylation and glutathione S-transferation in scoparone-treated group were not significantly different from those of the control group.

• Preventive Nutrition and Food Science
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• 제9권1호
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• pp.53-57
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• 2004

The purpose of this study was to investigate the effects of green tea catechin on mixed function oxidase system (MFO), lipofuscin contents, carbonyl value, oxidative damage and the antioxidative defense system in lung of microwave exposed rats. Experimental groups were divided to normal group and microwave exposed group. The microwave exposed groups were subdivided into three groups: catechin free diet (MW-0C) group, 0.25% catechin (MW-0.25C) group and 0.5 ％ catechin (MW-0.5C) group according to the levels of dietary catechin supplementation. The rats were irradiated with microwave at frequency of 2.45 GHz for 15 min. Experimental animals were sacrificed at 6th day after microwave irradiation. The contents of cytochrome P$_{450}$ contents in MW-0C group was increased to 95% , compared with normal group. MW-0.25C and MW-0.5C groups were reduced to 16% and 31%, respectively, compared with MW-0C group. The activity of NADPH-cytochrome P$_{450}$ reductase in MW-0C group was increased to 44%, compared with normal group. MW-0.25C and MW-0.5C groups were reduced to 12% and 17％, respectively, compared with MW-0C group. The activity of superoxide dismutase (SOD) in MW-0C group was decreased to 21 ％, compared with normal group. MW-0.25C and MW-0.5C group were significantly (p < 0.05) increased, compared with MW-0C group. The activity of glutathione peroxidase (GSHpx) in MW-0C group was significantly decreased, compared with normal group. MW-0.25C and MW-0.5C groups were recovered to the level of normal group. The thiobarbituric acid reactive substances (TBARS) content in MW-0C group was increased to 34 ％, compared with normal group. Catechin supplementation groups were maintained the level of normal group. The levels of caybonyl value in MW-0C group was increased to 21 ％, compared with normal group. MW-0.25C and MW-0.5C groups were reduced to 14% and 12%, respectively, compared with MW-0C group. The lipofuscin contents in MW-0C group were increased to 23.4 ％, compared with normal group. That of MW-0.5C group was significantly reduced, compared with MW-0C group. In conclusion, MFO system was activated and the formation of oxidized protein, lipofuscin was increased and antioxidative defense system was weakened of lung tissue in microwave exposed rats, thus oxidative damage was increased. But it was rapidly recovered to normal level by green tea catechin supplementation.n.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.172-172
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• 1993

Acetaminophen(이하 AAP)은 간의 mixed function oxidase system에 의해 toxic metabolite로 대사되어 간괴사를 일으킨다. 최근에는 지금까지 임상적으로 사용되어온 한약이나 생약의 cytochrome P450의 활성과 간의 glutathion 합성에 미치는 영향에 대한 연구가 활발하게 진행되고 있다. 본 연구에서는 AAP의 간독성을 억제하는 물질을 규명하고자 민간이나 한방에서 보간 또는 해독제로 많이 사용되고 있는 생약을 screening하였다. 그 결과 간의 약물대사 효소계에 엉힝을 미치는 것으로 보고된 강활(Angelica koreana)과 민간이나 한방에서 간질환치료의 목적이나 해독제로 쓰여온 시호(Buplerum falcatum), 토복령(Smilax china) 및 금은화(Lonicera japonica)가 AAP로 유발된 간독성에 미치는 효과를 살펴보았다. 방법: 예비실험을 통해 강활, 시호, 토복령 및 금은화의 MeOH ext.가 AAP로 유도된 간독성에 방어효과가 있음을 확인하고 이를 hexane, ether, ethyl acetate 및 butanol로 계통분획하여 랫트에 전처치한 후 고농도의 AAP를 투여하여 간 손상을 일으키고 혈청중의 효소활성과 지질ㆍcholesterolㆍbilirubin함량 등을 측정하였다.

• 생명과학회지
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• 제8권6호
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• pp.695-701
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• 1998

한국산 꽃뱀(Natrix tigrina Lateralis)의 간 마이크로좀에 존재하는 mixed function oxidase system 구성 성분들의 함량과 P45O 의존성 monooxygenase의 활성도를 조사하고 이들을 흰쥐(Sp. D)의 것과 상호 비교하였다. 꽃뱀에서의 P45O, b5 함량 및 NADPH-cytochrome c reductase 활성도는 흰쥐에서 보다 낮았으며, 7-ethoxycoumarin O-deethylase와 benzphetamine N-demethylase 활성도 역시 흰쥐에서 보다 상당히 낮았다. 그러나 aryl hydrocarbon hydroxylase와 testosterone hydroxylase 활성도는 흰쥐와 비교할 때 거의 비슷하거나 오히려 높았다. Testosterone의 수산화 반응에 대한 선택특이성을 조사한 결과, 꽃 뱀은 7$\alpha$ 위치에서, 흰쥐는 6$\beta$ 위치에서 가장 높은 수산화 반응물을 생성했다. 그러나 testosterone의 C2와 C3 위치에서의 수산화 반응에 대한 선택특이성은 꽃뱀과 흰쥐에서 비슷하였다. Radioimmunoassay (RlA)를 실시하여 5종 (CYP2B, CYP1A1, CYP1A2, CYP3A 및 CYP2El)의 P45O 동위효소의 구성비를 비교한 결과, 꽃뱀에서는 CYP1A1/1A2가, 흰쥐에서는 CYP2El이 각각 비교적 많이 존재하였다. 부분정제한 P45O을 SDS-PAGE와 RIA로 분석한 결과, 꽃뱀의 간 마이크로좀에 존재하는 P45O중에는 흰쥐와는 다른 종류의 P45O 동위효소가 존재함을 시사하였다.