• 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.

• 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.

• Archives of Pharmacal Research
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• 제11권2호
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• pp.122-126
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• 1988

The effects of psoralen and angelicin on hepatic microsomal drug-metabolizing enzyme (DME) activities were investigated to elucidate the mode of the interaction of furanocoumarins with DME system. A single administration (30 mg/kg,i. p.) of both coumarins to mice cased a significant prolonagation of hexobarbital-induced hypnosis as well as an increase in strychnine toxicity. The inhibitory potencies of both coumarins as measured by rat hepatic microsomal aminopyrine N-demethylase and hexobarbital hydroxylase activities in vitro were considerably weaker than those of other furanocoumarins which possess a side chain moiety. Both coumarins were found to have significant inducing effects of DME system, with repeated treatments of them. The activities of an angular coumarin were stronger than those of a linear coumarin.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.205-205
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• 1996

본 실험은 간장허혈 및 재관류시 야기되는 간장 손상에 대해 vitamin C와 E 각각의 효과와 이들의 병용효과를 알아보고자 하였다. 실험군은 흰쥐에 vitamin E(25mg/kg)를 실험전 3일간 투여한 군, vitamin C(100mg/kg)를 실험 5분전 경정맥주사한 군 및 vitamin C와 E의 병용 투여군등의 3군으로 하여 각각에 허혈을 유발시킨 후 (60분) 재관류 1시간, 5시간에 간세포 손상정도(AI.T, AST, liver wet-weight to dry-weight ratio), 지질과산화(MDA), 담즙분비변동(bile flow, bilirubin, cholate output) 및 약물대사효소계의 변동(cytochrome P$_{450}$, aminopyrine-N-demethylase, aniline p-hydroxylase activity) 등을 관찰하였다. 실험결과로는 허혈 및 재관류로 인한 ALT, AST MDA는 재관류 5시간에 최고치를 이루었으며 이는 vitamin C와 vitamin E의 각각 투여로 억제되었고, 특히 vitamin C와 E의 병용투여로 더욱 현저하게 억제되었다. 간세포 부종의 지표인 liver wet-weight to dry-weight ratio도 vitamin C와 E의 병용투어로 유의성있게 억제되었다. 담즙분비량 및 담즙산량은 vitamin C 투여와 vitamin C와 E 병용투여로 허혈 및 재관류로 감소된 양을 증가시켰고, 특히 vitamin C와 E의 병용투여는 담즙분비량에 있어 현저한 상승을 나타내었다. 허혈 및 재관류로 인한 cytochrome P$_{450}$양의 감소와 aminopyrine N-demethylase 활성의 억제는 vitamin C 투여와 vitamin C와 E의 병용투여에 의해 유의성 있게 증가하였다. 이상의 결과로 보아 vitamin C와 vitamin E는 각각 허혈 및 재관류로 인한 간장손상을 완화시켰으며 특히 vitamin C와 E의 병용투여는 상승적으로 적용하여 간세포손상을 더욱 억제시킴을 알 수 있었다.

• Preventive Nutrition and Food Science
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• 제4권4호
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• pp.260-264
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• 1999

Korean traditional fermented soy paste (doenjang) prolonged the life span of Balb/c mice injected with the sarcoma-180 cells. The activities of liver enzymes, such as xanthine oxidase, aminopyrine N-demethylase, aniline hydroxylase, ${\gamma}$-glutamylcysteine synthetase, glutathione reductase and glutathione S-transferase (GST), and the contents of lipid peroxide and glutathione were determined from the sarcoma-180 cell injected mice that were treated with methanol extracts from doenjang, miso and soybean. The content of lipid peroxide and the activity of xanthine oxidase in the liver of Balb/c mice which were increased by the transplantation of the sarcoma-180 cells were decreased by treatment with the methanol extract from doenjang. But the activities of aminopyrine N-dementhylase and aniline hydroxylase were not affected by the treatment of methanol extracts from doenjang to the mice injected with the sarcoma-180 cells. The content of glutathione, the activities of glutamylcysteine synthetase, glutathione reductase and glutathione S-transferase decreased by the injection of the sarcoma-180 were recovered considerably by the treatment of the methanol extract from doenjang.