• Toxicological Research
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• 제5권1호
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• pp.17-25
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• 1989

Chronic adminstraction of morphine to adult male rats has long been known to lower hepatic cytochrome p-450 content and its dependent mixed-function oxidase activity. Following the treatment of adult male rats with morphine, pethidine pentazocine and codeine and also by concomitant adminstration of naloxone activities of microsomal electron transfer in the adult male rats were examined. In present study, the acute treatment of mature male rats with a dose of narcotic drugs higher than that used chronically also reduces their hepatic cytochrome p-450.

• 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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• 제11권2호
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• pp.215-221
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• 1995

This paper examines the effects of dietary polyunsaturated fatty acid/saturated fatty acid (p/s) ratios and butylated hydroxytoluene (BHT) on the hepatic microsomaI mixed-function oxidase sy. stem in 2~acetylaminofiuorene (2-AAF) treated rats. Sprague-Dawley male rats were fed the diet of beef tallow (p/s 0.08), beef tallow plus soybean oil (p/s 1.0), and soybean oil (p/s 4.0) at the level of 15%fat and with or without 0.3% BHT. After 2-AAF was injected twice at the ages of 23 and 27 weeks, cholesterol/phospholipid molar ratio, thiobarbituric acid reactive substances (TBARS) level, cytochrome P450, cytochrome $b_5$, NADPH-cytochrome $b_5$, and NADPH-cytochrome c reductase activity were measured from isolated hepatic microsomal fractions. In the beef tallow (p/s 0.08) and beef tallow plus soybean oil (p/s 1.0) groups, cholesterol/phospholipid molar ratio showed decreasing tendency by 2-AAF and BHT. Cytochrome P-450 content was decreased in the group of soybean oil (p/s 4.0) and NADPH-cytochrome c reductase activity was increased by 2-AAF and BHT in all the dietary groups. While TBARS levels were increased by 2-AAF in all the dietary groups, they were reduced by BHT in the soybean oil (p/s 4.0) group. These results suggest that long term intake of soybean oil (p/s 4.0) diet induced changes in the nature of microsomal membrane and induced less cytochrome P-450, low level feeding of BHT increased cytochrome c reductase activity and lowered microsomal lipid peroxidation levels, which were increased by 2-AAF treatment.

• 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.

• 한국식품영양과학회지
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• 제25권6호
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• pp.969-975
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• 1996

본 연구는 streptozotocin 유발 당뇨쥐의 간과 폐조직에서의 MFO계 활성 변화 및 지질과산화에 미치는 vitamin E의 영향을 관찰하고자 본 실험을 행하였다. 체중 140g 정도의 Sparague-Dawley종 숫컷을 대조군(40mg vitamin E/kg diet group)과 당뇨유발 실험군으로 나눈 후 실험군은 다시 식이내 vitamin E 공급수준에 따라 DM-0E군(0mg vitamin E/kg diet group), DM-40E군(40mg vitamin E/kg diet group), DM-400E군(400mg vitamin E/kg diet group) 나누어 4주간 사육한 후 대조군을 제외한 실험군을 STZ로 당뇨를 유발시켰다. 당뇨유발 6일 후 쥐를 희생시켜 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. 1. 간조직 중의 cytochrome P$_{450}$ 함량은 대조군에 비해 DM-0E군, DM-40E 군 및 DM-400E군이 각각 162%, 150%, 56% 증가하였으며 또 DM-400E군은 DM-0E, DM-40E군에 비해 낮았다. 폐조직 중의 cytochrome P$_{450}$ 함량도 간조직에 비해 함량은 낮았지만 경향은 비슷하였다. 2. 간조직 중의 cytochrome b$_{5}$은 대조군에 비해 DM-0E군, DM-40E군은 각각 70%, 53%씩 증가하였으나 DM-400E군은 대조군 수준이었다. 폐조직 중의 cytochrome b$_{5}$함량도 대조군에 비 해 DM-0E, DM-40E 및 DM-400E군에서 각각 149%, 116%, 50%씩 증가하였다. 3. 간조직에서의 cytochrome P$_{450}$ reductase 활성은 대조군에 비해 DM-0E군은 58%, DM-40E군에서는 47% 증가하였으며 DM-400E는 대조군 수준이었다. 폐조직에서도 간조직에서와 비슷한 경향이었다. 4. 간조직의 지질과산화물가는 대조군에 비해 DM-0E군, DM-40E군, DM-400E군이 각각 143%, 95%, 31%씩 높았다. 또 DM-400E군은 DM-0E, DM-40E군에 비해 약 50% 정도 낮았다. 폐조직에서도 경향은 비슷했는데 간조직 보다 과산화적 손상이 다소 높았다. 이상의 결과에서 STZ 유발 당뇨쥐에서는 MFO system의 활성이 증가되고 지질과산화가 촉진되었다. 그러나 식이 중의 vitamin E의 적절한 공급은 MFO system 활성이 저하되고 과산화적 손상이 현저하게 완화됨을 볼 수 있었다.

• 한국수산과학회지
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• 제36권6호
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• pp.573-577
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• 2003

Effects of 4-nonylphenol (4-NP) on mixed function oxygenase (MFO) in the kidneies of rockfish (Sebastes schlegeli) were investigated. The cytochrome P45O (CYP) contents and NADPH cytochrome P450 reductase, NADH cytochrome b5 reductase and 7-ethoxyredorufin-O-deethylase (EROD) activities of microsome, glutathione S-transferase (GST) activity of cytosol in rockfish exposed to 4-NP for 7 days using an intraperitoneal injection (25 mg/kg) were quantitatively determined. The GST activity of rockfish exposed to 4-NP were higher, up to 5.2 times higher, than those in the control fish. The activities of NADPH-and NADH-dependent reductases were inhibited. On the other hand, CYP contents and EROD activity of the 4-NP exposed fish demonstrated neither an increasing or decreasing trend.

• Journal of Nutrition and Health
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• 제33권6호
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• pp.619-624
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• 2000

The purpose of this study was to investigate the effects of vitamin E on microsomal mixed function oxidase system of kidney in streptozotocin(STZ) induced diabetic rats. Sprague-Dawley male rats weighing 140$\pm$10g were randomly assigned to one control and three STZ-diabetic groups which were subdivided into vitamin E free diet(DM-0E group) 40mg vitamin E per kg diet(DM-40E group) and 400mg vitamin E per kg diet(DM-400E group). Vitamin E level of normal group was 40 mg per kg diet. Diabetes was experimentally induced by intravenous administration of 55 mg/kg B.W of STZ in citrate buffer(pH4.3) after 4 weeks feeding of experimental diets. Animals were sacrificed at the 6th day of diabetic state. The contents of cytochrome P450 in kidney were increased by 82, 54, 41% in DM-0E, DM-40E and DM-400E groups respectively when compared with normal group. The contents of cytochrome b5 in kidney were increased by 28% in DM-0E when compared with normal group but those of DM-40E and DM-400E groups were similar to that of normal group. The activities of NADPH-cytochrome P450 reductase in kidney that were increased by 35% in DM-0E group. Levels of TBARS(thiobarbituric acid reactive substance) in kidney were increased by 207, 129% and 72% in DM-0E and DM-400E groups respectively when compared with normal group but those of DM-40E and DM-400E groups were 26,44% lower than that of DM-0E groups. It is know that the activities of MFO system and lipid peroxidation were inhibited in kidney of STZ-induced diabetic rat by administeration of high doses of vitamin E.(Korean J Nutrition 33(6) : 619~624, 2000)

• 한국식품영양과학회지
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• 제27권2호
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• pp.319-325
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• 1998

The purpose of this study was to investigate the effect of green tea catechin on microsomal mixed function oxidase(MFO) system of kidney and brain in streptozotocin(STZ) induced diabetic rats. Sprague-Dawley male rats weighing 140$\pm$10g were randomly assigned to one control and three STZ-diabetic groups. Diabetic groups wer classified to DM-0C(catechin 0%/kg diet), DM-0.5C (catechin 0.5%/kg diet), and DM-1.0C(catechin 1%/kg diet) according to the level of catechin supplementation. Diabetes were experimentally induced by intravenous administration of 55mg/kg body weight of STZ in citrate buffer(pH 4.3) after 4 weeks feeding of three experimental diets. Animals were sacrificed at the sixth day of diabetic state. The contents of cytochrome P450 in kidney were increased by 77, 42, 49% in DM-0C, DM-0.5C and DM-1.0C groups, respectively, than normal group. The contents of cytochrome P450 in brain were increased by 43% in DM-0C group than normal group, but those of DM-0.5C and DM-1.0C groups were similar to that of normal group. The contents of cytochrome b5 in kidney were increased by 78, 38, 49% in DM-0C, DM-0.5C and DM-1.0C groups, respectively, than normal group. Meanwhile, the contents of cytochrome b5 in brain were not significantly different among all groups. The activities of NADPH-cytochrome P450 reductase in kidney of DM-group were increased by 27% than normal group, but those of DM-0.5C and DM-1.0C groups were 13 and 15% lower than that of DM-0C group. The activities in brain were also increased by 31% in DM-0C group, but those of DM-0.5C and DM-1.0C groups were similar to than of normal group. Levels of TBARS (thiobarbituric acid reactive substance) in kidney were increased by 147, 60 and 59% in DM-0C, DM-0.5C, and DM-1.0C groups, respectively, compared with normal group, but those of DM-0.5C and DM-1.0C groups were 36, 35% lower than that of DM-0C group. Meanwhile, the levels of TBARS in brain were not significantly different among four groups. These results indicate that dietary catechins in green tea play a powerful antioxidant role in reducing the lipid peroxidation enhanced by activation of MFO system in STZ-induced diabetes.

• 환경생물
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• 제22권1호
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• pp.177-183
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• 2004

유기주석화합물인 tributyltin chloride (TBTC), tributyltin oxide (TBTO)와 triphenyltin chloride (TPTC)를 넙치 간장으로 만든 미크로좀에 in vitro적으로 노출시켜서 이들 화합물의 대사에 관여하는 mixed function oxidase (MFO) 중 cytochrome P450 (CYP) 농도와 7-ethoxyresorufin deethylase (EROD) 활성의 변화를 조사하였으며, 또한 in vivo 실험에서는 TPTC를 넙치에게 복강주사(7.5 mg $kg^{-1}$ BW)하여 간장의 MFO (CYP농도, NADPH cytochrome c 환원효소 활성, NADH chtochrome b5 환원 효소 활성, EROD 활성) 반응을 경시적으로 조사하였다. 그 결과, in vitro에서는 TBTC, TBTO 및 TPTC가 모두 CYP 농도와 EROD 활성을 저해하였으며, 저해력은 TPTC가 가장 컸고 이어서 TBTO, TBTC의 순이었다. 유기주석화합물의 노출농도와 노출시간과 비례하면서 저해정도가 커졌으며, 특히 EROD활성의 저해는 노출농도에 크게 의존적이었다. 그리고 in vivo실험에서도 유기주석 화합물은 CYP농도, NADPH cytochrome c 환원효소 활성, NADH cytochrome b5 환원효소 활성, EROD 활성을 억제하였다. EROD 활성은 오염물질에 의한 반응이 민감하고 재현성도 있어 바람직한 측정지표로 이용될 수가 있을 것이다.

• 대한수의학회지
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• 제38권1호
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• pp.17-28
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• 1998

Drug-metabolizing activities of Korean native cattle and swine were investigated from viewpoints of the cytochrome P-450's level, their dependent mixed function oxidase activities, the reactive oxygen species formation and cytosolic enzyme acitivities from each liver homogenates. Level of cytochrome P-450 in the liver microsome of Korean native cattle was $0.28{\pm}0.05nmole/mg$ and that in pigs $0.35{\pm}0.03nmole/mg$. Level of cytochrome $b_5$ of Korean native cattle was $0.24{\pm}0.06nmole/mg$, and that of pigs $0.2{\pm}0.05nmole/mg$, showing no difference between two species. NADPH P-450 reductase were higher in Korean native cattle ($58.3{\pm}5.3nmole/mg/min$) than in pigs ($29.9{\pm}3.8nmole/mg/min$)(p<0.01). The activities of cytochrome P-450 dependent monooxygenases such as ethoxyresorufin O-deethylase (cattle, $96.5{\pm}12.5nmole/mg/min$ ; pigs, $13.6{\pm}2.1nmole/mg/min$), N-benzphetamine N-demethylase (cattle, $5.23{\pm}0.82nmole/mg/min$ ; pigs, $0.76{\pm}0.3nmole/mg/min$) and aniline hydroxylase (cattle, $0.95{\pm}0.1nmole/mg/min$ ; pigs, $0.33{\pm}0.08nmole/mg/min$) were much higher in Korean native cattle than in swine(p<0.01). However, the activity of testosterone $7{\alpha}$-hydroxylase was higher in swine ($90.4{\pm}1.2nmole/mg/min$) than cattle (cattle, $32.8{\pm}1.2nmole/mg/min$). Interestingly, testosterone $16{\alpha}$-hydroxylase, a marker enzyme for P-450 IIA was not detected in both animal species. These results suggest that Korean native cattle and pigs have high contents of P-450 IA1 and P-450 IIIA. Total sulfhydryl compound (cattle, $10.3{\pm}1.1nmole/mg$ ; Pigs, $14.5{\pm}1.8nmole/mg$) and glutathione related enzymes except glutathione reductase (cattle, $38.1{\pm}7.9nmole/mg/min$; swine, $22{\pm}3.6nmole/mg/min$) showed higher levels in swine than in Korean native cattle. Superoxide dismutase (cattle, $7.64{\pm}0.84nmole/mg/min$ ; pigs, $4.47{\pm}0.94nmole/mg/min$) and catalase (cattle, $30.4{\pm}3.7nmole/mg/min$ ; pigs, $17.2{\pm}1.8nmole/mg/min$) were remarkably higher in Korean native cattle than in swine (p<0.05).