• Archives of Pharmacal Research
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• 제9권2호
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• pp.81-86
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• 1986

The effect of imperatorin on hepatic microsomal mixed function oxidases (MF0) was investigated. On acute treatment, imperatorin (30 mg/kg, i.p) caused a significant reduction in activities of hepatic aminopyrine N-demethylase, hexobarbital hydroxylase and aniline hydroxylase as well as cytochrome p0450 content in rats and mice. Kinetic studies on rat liver enzymes revealed that imperatorin appeared to be a competitive inhibitor of aminopyrine N-demethylase (Ki,0.007 mM), whereas a non-competitive inhibitor of hexobarbital hydroxylase (Ki, 0.0148 mM). Imperatorin also inhibited non-competitively aniline metabolism (Ki 0.2 mM). Imperatorin binds to phenobarbital-induced cytochrome p-450 to give a typical type 1 binding sepctrum (max. 388nm, min 422 nm). Multiple administrations of imperatorin (30 mg/kg. i. p. daily for 7 days) to mice shortended markedly the duration of hexobarbital narcosis and increased activities of hepatic aminopyrine N-demethylase and hexobarbital hydroxylase and the level of cytochrome p-450 where as aniline hydroxylase activity was unaffected.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1988년도 학술대회지
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• pp.81-86
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• 1988

고려인삼에서 분리한 폴리아세틸렌 성분인 파낙시돌, 파낙시놀과 파낙시트리올의 사염화탄소로 유도된 마우스와 흰주의 지질과 산화와 효소적 또는 비효소적으로 유도된 시험관내 과산화 지질 형성에 미치는 영향을 관찰하였다. 정상 또는 사염화탄소 처리된 마우스와 흰쥐에 대한 폴리아세틸렌의 효과를 혈청과 간 과산화 지질수준과 혈청효소 (GOT, GPT, LDH) 활성을 측정함으로써 관찰하였다. 간 마이크로좀 내 cytochrome P-450 함량과 aniline hydroxylase와 aminopyrine demethylase 활성도 측정되었다. 정상 마우스에 폴리아세틸렌을 처리한 경우 파낙시놀의 경우를 제외하곤 간과 혈청의 과산화 지질 형성과 혈청효소들의 활성에 변화가 없었으며, 파낙시놀은 간의 지질 과산화를 억제하였다, 폴리아세틸렌 성분들은 사염화탄소로 유도된 간의 과산화지질형성에 대한 보호작용을 나타내었고, 혈청지질과산화 수준을 낮추었다. 또한 사염화탄소로 유도된 LDH의 혈액내 유출에 대한 보호작용이 있으나, 혈청 GOT와 GPT 수준엔 영향을 주지 않았다. 사염화탄소는 cytochrome P-450 함량과 aniline hydroxylase, aminopyrine demethylase 활성을 낮추었으며, 이 경우 폴리아세틸렌은 효과를 나타내지 못하였다. 반면, 사염화탄소 없이 폴리아세틸렌만 처리한경우, 파낙시돌과 파낙시놀은 aniline hydroxylase를 세폴리아세틸렌성분은 aminopyrine demethylase를 유도하였으며, cytochrome P-450엔 영향을 주지 않았다. 시험관내 간 마이크로좀의 지질 과산화는 폴리아세틸렌 첨가시 농도에 비례하여 억제되었다.

• 한국동물학회지
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• 제27권4호
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• pp.221-230
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• 1984

Wistar계 흰쥐 간의 약 70%를 절제한 후 재생중인 나머지 간의 microsome에서 lipid peroxidation과 약물 대사효소중 특징적인 aminopyrine demethylase의 활성도를 측정하고 NADPH-cytochrome c reductase, glutathione peroxidase의 활성도와 cytochrome P-450의 함량을 측정하였다. Aminopyrine demethylase의 활성도는 재생 제1일에 최저치를 나타냈으며 재생이 진행될수록 정상인 수준으로 증가하였고 lipid peroxidation, NADPH-cytochrome c reductase, cytochrome P-450의 함량 역시 재생초기에 급히 감소하여 재생2일에 가장 낮은 값을 나타내며 점차 정상인 수준으로 증가하여 7일 이후에는 정상치에 도달하였다. Glutathione peroxidase의 활성도는 재생중인 간이나 정상인 개체의 간에서 별다른 차이가 없었다. 이것은 재생중인 간에서 재생초기에 cytochrome P-450의 함량과 NADPH-cytochrome c reductase의 활성도 감소가 lipid peroxidation과 약물 대사효소의 활성도 감소를 일으키며 이러한 현상은 부분 간 절제 후 7일 이후에는 거의 나타나지 않았다.

• 약학회지
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• 제28권1호
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• pp.53-59
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• 1984

Drug-metabolizing system which has the important role in drug metabolism is localized in smooth endoplasmic reticulum of hepatocytes and is composed of NADPH, NADPH-cytochrome $P_{450}$ reductase, cytochrome $P_{450}$ and others. It is well known that the enzyme system is induced by phenobarbital and methylcholanthrene. Lipid peroxidation is reaction of oxidative deterioration of polyunsaturated lipids. Formation of lipid peroxides in liver microsome has been found to produce degradation of phospholipid, which are major components of microsomal membrane. The relationship between the formation of lipid oxides and the activities of drug-metabolizing enzyme in the liver of rats was reported by several investigators. In this study the effect of riboflavin tetrabutylate, an antioxidant on lipid peroxidation, specially the relationship between lipid peroxidation and drug-metabolizing enzyme system was investigated. In addition the effect of vitamin A derivatives, such as retinoic acid and retinoid on the enzyme was also observed. Results are summarized as followings. 1) The pretretment with riboflavin tetrabutylate inhibited completely the lengthened sleeping time due to $CCl_{4}$ treatment. 2) The increase of TBA value was prevented by the pretreatment with riboflavin tetrabutylate. 3) The pretreatment with riboflavin tetrabutylate also prevented the decrease of drug-metabolizing enzyme caused by $CCl_{4}$. 4) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity.

• 약학회지
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• 제40권4호
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• pp.449-455
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• 1996

Betaine is one of the major water-soluble components in Lycii Fructus. In the present study the effect of repeated betaine treatment on the hepatotoxicity and the cytochrome P-4 50-dependent enzyme system was examined in adult female rats. Administrations of betaine (100 or 1,000mg/kg/day, ip) to rats repeatedly for 4 or 9 days did not evoke hepatotoxic response as determined by increases in glutamic pyruvic transaminase(GPT) and glutamic oxaloacetic transaminase(GOT) activities measured 24 hours following the final dose of betaine. The activities of aminopyrine N-demethylase, p-nitroanisole O-demethylase and p-nitrophenol hydroxylase as well as the contents of cytochrome P-450 were determined in hepatic microsomes of rats treated with betaine(1,000mg/kg/day, ip) for 4 or 9 days. Repeated treatment of rats with betaine for a period of 4 days induced a marginal decrease in the contents of cytochrome P-450, but did not influence the activities of p-nitrophenol hydroxylase, p-nitroanisole O-demethylase, or aminopyrine N-demethylase. Extension of the betaine treatment to 9 consecutive days failed to alter the parameters for hepatic drug metabolizing activity determined in the present study. Since repeated large doses of betaine were demonstrated to be tolerated by rats without showing any toxicity or changes in drug metabolizing enzyme activities in the liver, this compound appears to be relatively safe to animals upon long-term ingestion.

• Toxicological Research
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• 제12권2호
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• pp.265-270
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• 1996

Effects of a single administration of dichloromethane (DCM) on the hepatic drug metabollzing activity were determined using adult female rats. Rats were treated with DCM (3 mmol/kg, ip) and the disappearance of antipyrine (100 mg/kg, iv) or ethanol (2 g/kg, ip) from blood was measured. The blood concentration and half-life of antipyrine was not influenced by DCM administration. And DCM did not alter the blood concentration of ethanol measured for 240 min after the treatment. The effect of DCM treatment on in vitro cytochrome P-450-dependent enzyme activities was examined as well. No significant difference in either aniline hydroxylase or aminopyrine N-demethylase was observed in hepatic microsomal fractiorts of rats treated with DCM 24 hr prior to sacrifice. The present study indicates that acutely given DCM does not alter the metabolism of xenobiotics in vivo. The failure of DCM to alter the in vitro hepatic microsomal drug metabolizing activity was also noted.

• 생약학회지
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• 제31권2호
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• pp.228-234
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• 2000

Effects of Houttuynia cordata on the level of lipid peroxide and the enzyme activities of the liver were investigated in bromobenzene-induced rats. Lipid peroxide content in liver was increased by bromobenzene. It was decreased when the methanol extract from the aerial parts of H. cordata was treated to the rat. The methanol extract reduced the activities of aminopyrine N-demethylase and aniline hydroxylase that increased by bromobenzene, however did not affect glutathione S-transferase activity. The methanol extract recovered the activity of epoxide hydrolase activity that decreased significantly by bromobenzene. We suggest that under our experimental conditions the extract might play an important play in the prevention of hepatotoxicity by reduction of aminopyrine N-demethylase and aniline hydroxylase activities as well as enhancement of epoxide hydrolase activity. Six phenolic compounds have been isolated from H. cordata and identified by means of spectral analysis as protocatechuic acid, quercetin, apigenin, afzelin, hyperoside and quercitrin.

• 생명과학회지
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• 제13권2호
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• pp.230-235
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• 2003

Bromobenzene으로 간독성을 유발한 흰쥐에 생열귀나무 뿌리를 투여하여 bromobenzene 대사계에 미치는 효소활성을 관찰하였다. Bromobenzene은 bromobenzene 2,3-oxide와 bromobenzene-3, 4-oxide로 전환되며, 3,4-oxide는 독성물질로서 epoxide hydrolase에 의해 무독성 bromobenzene-3,4-dihyrodiol로 대사 또는 glutathione S-transferase에 의하여 배설되기도 한다. 중국 민간에서 강장제로 사용하는 생열귀나무는 한방에서 소화불량, 위통 등의 치료에 사용되는 약용식물이다. 생열귀나무의 뿌리 추출물은 흰쥐의 간 epoxide 생성계에 관여하는 aminopyrine N-demethylase, aniline hydroxylase 활성과 epoxide를 대사시키는 glutathione S-transferase 활성에는 변화를 주지 않았다. 그러나 생열귀추출물 500 mg/kg 경구투여군은 eporide를 무독화시키는 epoxide hydrolase 활성에서 bromobenzene 투여로 효소활성이 저하된 대조군보다 33% 활성을 회복시켰다. 따라서 생열귀나무 뿌리는 간독성물질인 bromobenzene 대사에 관여하는 epoxide hydrolase 활성 증가로 인해 간보호작용이 일어나는 것으로 판단된다.

• Biomolecules & Therapeutics
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• 제2권2호
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• pp.141-148
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• 1994

This study was done to determine whether specific alterations exist in hepatic microsomal function after varying periods of ischemia (IS) and reperfusion (RP) during microsomal lipid peroxidation occurs. Rats were pretreated with $\alpha$-tocopherol to inhibit lipid peroxidation or with vehicle (soybean oil). Control animals were time-matched sham-ischemic animals. Four groups of animals were studied: Group 1 (sham), group 2 (30 mins IS), group 3 (60 mins IS) and group 4 (90 mins IS). After 1, 5 or 24 hr of reperfusion, liver microsomes were isolated and cytochrome P-450s were studied. In all vehicle-treated ischemic rats, serum ALT levels peaked at 5 hr and were significantly reduced by $\alpha$-tocopherol pretreatment. Similarly, microsomal lipid peroxidation was elevated in all vehicle-treated ischemic animal groups, but this elevation was prevented by $\alpha$-tocopherol pretreatment. Cytochrome P-450 content was significantly decreased in both group 3 and group 4. In all vehicle-treated ischemic animal groups, aminopyrine N-demethylase activity was significantly decreased for the entire reperfusion period. $\alpha$-Tocopherol inhibited reductions of cytochrome P-450 content and aminopyrine N-demethylase activity at both 1 hr and 5hr of reperfusion but did not affect the reduced levels of cytochrome P-450 content and aminopyrine N-demethylase activity at 24 hr of reperfusion. Aniline p-hydroxylase activity was significantly decreased in group 4, whereas it was increased in group 3. These decreases and increases were prevented by $\alpha$-tocopherol pretreatment. Our finding suggests that abnormalities in microsomal drug metabolizing function occur during hepatic ischemia and reperfusion in vivo and this is attributed to microsomal lipid peroxidation.

• 한국식품과학회지
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• 제32권5호
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• pp.1179-1185
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• 2000

멸치액젓의 용매분획을 $50^{\circ}C$에서 10일동안 항온실험한 경우 각 용매분획의 건조중량 10 ${\mu}g$ 또는 20 ${\mu}g$이 5 mg의 linoleic acid의 자동산화를 저해하는 것으로 나타났으며, 용매분획 중 부탄올분획 및 수용액분획이 염분을 함유하고 있었고 염분의 함량은 각각 12.2% 및 21.1%이었다. 흰쥐에게 간장독성을 유발시킨다고 알려진 bromobenzene을 주사하고 간조직을 분리하여 in vitro에서 멸치액젓이 간균질액의 지질과산화물 생성에 미치는 효과를 관찰한 결과, 모든 용매분획들이 3 mg/mL 또는 1 mg/mL 농도에서 지질과산화물 생성을 강하게 감소시켰으며 수용액분획의 경우 0.3 mg/mL 농도에서도 활성을 가지는 것으로 나타났다. 간조직의 지질과산화반응에 관여하는 것으로 알려진 효소들 중 aniline hydroxylase, aminopyrine N-demethylase, xanthine oxidase 및 aldehyde oxidase 활성에 대한 멸치액젓의 효과를 관찰한 결과, 간세포 마이크로솜 분획에 존재하는 aniline hydroxylase 및 aminopyrine N-demethylase의 활성을 모든 용매분획이 저해하였다. 즉, 3 mg/mL 농도에서는 거의 정상쥐의 효소활성 수준까지 회복시켰고, 0.3 mg/mL의 농도에서도 유의적인 효과가 나타났으나 세포질 효소인 xanthine oxidase 및 aldehyde oxidase의 활성에 대하여는 저해효과가 나타나지 않았다. 이와 같은 결과로부터, bromobenzene-유도 간지질의 과산화물 생성과정에 있어서 멸치액젓의 항산화물질들은 free radical을 포획하여 지질과산화물 생성을 억제하는 것이 아니라 epoxide생성단계를 저해하여 과산화지질 생성을 억제하는 것으로 사료된다.