• Toxicological Research
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• 제13권4호
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• pp.371-376
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• 1997

To compare the severe liver damage with the slight one on the bromobeazene metabolism in rats, the animal group described as B7 group was induced the stage of slight liver damage with 7 times bromobenzene injection every other day (400 mg/Kg body wt. i.p.), whereas B40 group was induced that of more severe liver damage with bromobeazene 40 times injection as identified with determination of serum levels of alanine aminotransferase(ALT) activity and the histopathological findings. In the present experimental animal model, the decreasing rate of glutathione(GSH) and the increasing rate of glutathione S-transferase activity to the control group were higher in B7 group than B40 group. Furthermore the single dose of bromobenzene was injected to the two groups and sacrificed at 8hr and the hepatic aniline hydroxylase(AH) activity, GSH content and GST activity were determined. The increasing rate of AH activity to the control was lower in B40 group than B7 group and the decreasing rate of GSH to the control was also lower in B40 than B7 group. Moreover, B7 group showed the increased activity of hepatic GST to the control whereas B40 group showed the decrease activity of the enzyme. And Vmax value in GST was more decreased in B40 group than B7 group.

• Archives of Pharmacal Research
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• 제26권1호
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• pp.47-52
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• 2003

The aim of this study was to investigate the effects of trauma on alterations in cytochrome P450 (CYP 450)-dependent drug metabolizing function and to determine the role of Kupffer cells in hepatocellular dysfunction. Rats underwent closed femur fracture (FFx) with associated soft-tissue injury under anesthesia, while control animals received only anesthesia. To deplete Kupffer cells in vivo, gadolinium chloride (GdCl$_3$) was injected intravenously via the tail vein at 7.5 mg/kg body wt., 1 and 2 days prior to FFx surgery. At 72 h after FFx, serum alanine aminotransferase (ALT) activity was increased, and this increase was attenuated by GdCl$_3$ pretreatment. Serum aspartate aminotransferase (AST) and lipid peroxidation levels were not changed by FFx. Hepatic microsomal CYP 450 content and aniline p-hydroxylase (CYP 2E1) activity were significantly decreased; decreases that were not prevented by GdC1$_3$. The level of CYP 2B1 activity was decreased by Kupffer cell inactivation, but not by FFx. There were no significant differences in the activities of CYP 1A1, CYP 1A2 and NADPH-CYP 450 reductase among any of the experimental groups. Our findings suggest that FFx trauma causes mild alterations of hepatic CYP 450-dependent drug metabolism, and that Kupffer cells are not essential for the initiation of such injury.

• 동아시아식생활학회지
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• 제4권1호
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• pp.105-112
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• 1994

To evaluate the role of dietary earthworm flour in liver injury by CCl4 treatment, the rats were fed 5% earthworm flour supplemented diet for 53 days and control rats were fed standard diet without earthworm supplementation. Liver damage was induced both in earthworm flour supplemented diet and control groups by two intraperitoneal injections of CCl4 at the level of 0.1$m\ell$/100g body weight(50% in olive oil) at intervals of 16 hours the increasing rate of lover weight/body weight(%) and serum levels of alanine aminotransferase activity to the control group were higher in CCl4-treated rats fed earthworm flour supplemented diet than those fed standard diet. The decreasing rate of hepatic microsomal aniline hydroxylase activity was also higher in rats fed earthworm supplemented rats by the CCl4 treatment, Hepatic glutathione S-transferase activity was sinificantly higher in rats fed earthworm supplemented diet than those fed standard diet. It is concluded that a dietary earthworm flour argument the metabolic rate of CCl in rats.

• 약학회지
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• 제40권5호
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• pp.574-581
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• 1996

The study was initiated to elucidate the protective mechanism by examining in vivo effect of some marine natural products, Styela plicata, Ecklonia stolonifera and Pachymeniopsis elliptica on acetaminophen-induced lipid peroxidation. The methanol extract of S. plicata prevented acetaminophen (800mg/kg, i.p.)-induced hepatotoxicity in rats as evidenced by the decreased formation of lipid peroxide. But the methanol extracts of E. stolonifera and P. elliptica were not affected on the formation of lipid peroxidation. The activities of cytochrome P-450, animopyrine N-demethylase and aniline hydroxylase were not changed by the treatment with S. plicata in comparison with acetaminophen-teated group. In acetaminophen-treated control rats, the glutathione S-transferase activity was decreased markably. However. in S. plicata pretreated group, the effect caused by acetaminophen was markably reduced. A-cetaminophen decreased the level of hepatic, glutathione, which was restored to same degree by S. plicata pretreatment. And activity of ${\gamma}$-glutamylcystein synthetase was not changed by S. plicata pretreatment, but the activity of glutathione reductase was increased significantly.

• 생약학회지
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• 제28권4호
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• pp.239-246
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• 1997

The methanol extracts of some marine algae were tested for investigating the effects on the formation of lipid peroxide and the activities of free radical generating enzyme in vitro in bromobenzene-treated rat. The extracts of Enteromorpha compressa, Capsosiphon fulvescens, Gelidium amansii, Hizikia fusiformis, Sargassum siliquastrum and Sargassum thunbergii which decreased the formation of lipid peroxide, inhibited the activity of xanthine and aldehyde oxidases by adding of each extracts. Phloroglucinol isolated from Ecklonia stolonifera reduced bromobenzene-induced hepatic lipid peroxidation. This compound administered daily over one week before intoxication with bromobenzene did not affect the activities of aminopyrine N-demethylase, aniline hydroxylase and glu tathione S-transferase. Epoxide hydrolase activity was decreased by bromobenzene, which was restored by pretreatment of phloroglucinol, The results suggest that the bromobenzene-induced hepatic lipid peroxidation by phloroglucinol is reduced by enhancing the activity of epoxide hydrolase.

• 대한한의학회지
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• 제16권2호
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• pp.320-336
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• 1995

SANGNYANGHYOLTANG(SYT) is one of the most important prescription that has been used in oriental medicine for diabetes mellitus. The sudy was done in order to elucidate the anti-diabetic effect of SYT. After pretreatment of SYT(1,000mg／kg) for 6 weeks, the effect of of SYT was prevented on serum liver function test and hepatic lipid peroxide content in rats i.v. injected with streptozotocin(STZ, 50mg／kg, tail vein) 5 weeks after pretreatment of SYT. The hepatic microsomal cytochrome P-450 and aniline hydroxylase were significantly decreased, and aminopyrine N-demethylase activity was significantly increased in SYT-STZ group as compared with control group. Changes in aldehyde oxidase, xanthine oxidase, superoxide dismutase, catalase, epoxide hydrolase, UDP-glucuronyltransferase and sulfotransferase activities were not significantly different in any of the group. The cytosolic glutathione S-transferase activity was significantly decreased in SYT-STZ group as compared with control group. The selenium-independent glutathione peroxidase was significantly increased in SYT-STZ group as compared with control group, but there was no significant difference in selenium-dependent glutathione peroxidase in any of the groups. The hepatic glutathione concentration was significantly increased in SYT-STZ group as compared with control group, and ${\gamma}-glutamylcystein$ synthetase and glutathione reductase activities were not significantly different in any of the groups. The hepatic lipid peroxide content, serum aminotransferase and sorbitol dehydrogenase activities were slightly decreased in significantly in SYT-STZ groups.

• 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.

• 혜화의학회지
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• 제8권1호
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• pp.593-623
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• 1999

This experimental study was designed to verify the anti-aging efficacy of Eukmigihwangtang (EMGHT) and Rehmannia Radix, and determine the specific role and actions of Rehmannia Radix. Normal rat (2 months old), aging rat (8 months old), and pathologically induced rat (2 months old, injected 30mg/kg of streptozotocin) are observed to study the aging eliciting factors such as peroxide contents and enzyme activities. The following results were obtained in this study: 1. For the body weight changes, normal group given Rehmannia Radix showed decrease in the body weight compared to the control group, aging group given EMGHT and Rehmannia Radix showed significant decrease in the body weight, and STZ injected group showed suppression to the body weight loss when given EMGHT and Rehmannia Radix. 2. For the content changes in serum lipid peroxide, normal group showed increasing level as the rat gets older. Aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant decrease in the lipid peroxide level compared to the control group. Decrease was more prominant in the group given EMGHT. 3. For the changes in serum hydroxyl radical, normal group did not show significant changes, but aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant decrease in the hydroxyl radical level compared to the control group. Decrease was more prominant in the group given EMGHT. 4. For the changes in serum superoxide dismutase (SOD) activity, normal group did not show significant changes, but aging group given EMGHT and Rehmannia Radix showed significant increase in the SOD activity compared to the control group. STZ injected group given EMGHT and Rehmannia Radix showed significant decrease in the SOD activity compared to the control group. 5. For the content changes in hepatic lipid peroxide, aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant decrease in the lipid peroxide level compared to the control group. 6. For the changes in hepatic cytochrome P-450 activity, aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant decrease compared to the control group. Cytochrome b5 activity was significantly decreased only in the STZ injected group given EMGHT and Rehmannia Radix. 7. For the changes in hepatic aminopyrine demethylase and aniline hydroxylase activity, aging group given EMGHT and Rehmannia Radix showed significant decrease compared to the control group. STZ injected group given EMGHT and Rehmannia Radix showed significant increase in the aminopyrine demethylase activity, and showed significant decrease in the aniline hydroxylase activity compared to the control group. 8. For the content changes in hepatic protein bound-SH and nonprotein bound-SH, againg group and STZ injected group given EMGHT and Rehmannia Radix showed significant increase compared to the control group. 9. For the content changes in hepatic glutathione level, aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant increase compared to the control group. 10. For the changes in hepatic glutathione S-transferase activity, aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant increase and decrease, respectively, compared to the control group. 11. For the changes in hepatic glutathione reductase activity, aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant increase compared to the control group, while $\gamma$-Glutamylcystein synthetase activity did not show significant changes. 12. For the changes in hepatic superoxide dismutase activity, aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant decrease compared to the control group. From the above results, the antioxidant effects of EMGHT and Rehmannia Radix were proved, as well as the role of Rehmannia Radix, a chief of EMGHT, was examined. In addition, since no change was reconized as the quantity of Rehmannia Radix and the order herbs increased, the reasonableness on EMGHT was proven with respect to its composition and quantity. Thus, the significance of EMGHT could be objectively exmined in terms of its composition and quantity. Considering animals used in the experiment, there were obvious changes in aging rats and pathologically induced rats than in normal rats. Consequently, it was noticeable that EMGHT and Rehmannia Radix were working selectively on the subjects.

• 한국식품영양과학회지
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• 제32권2호
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• pp.244-249
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• 2003

홍국 첨가식 이로 성장시킨 흰쥐에 있어서 간조직의 유해산소 기구와 혈청지질 성분의 변동에 어떠한 영향을 미치는지를 검토할 목적으로 Monascus로 제조된 홍국을 사료에 2%, 4% 첨가시켜 1개월 간 사육한 후, 처치하여 다음과 같은 결과를 얻었다. 300g 내외의 흰쥐를 홍국 첨가식 이로 1개월 간 성장시키는 동안 2% 홍국 첨가식이군의 체중증가율은 대조군 및 4% 홍국 첨가식이군보다 다소 낮게 나타나는 경향을 보였으며, 이러한 조건 하에서 간 기능은 2%, 4% 홍국첨가 식이군 모두 별다른 변화를 나타내지 않았다. 유해산소 생성 에 관여하는 cytochrome P450 dependent aniline hydroxylase 활성은 2% 및 4% 홍국 첨가식이군이 대조군에 비해서 각각 32%, 37%의 유의한(p<0.05)감소를 보였으며 홍국 첨가식이 농도를 달리한 실험군 간에 유의한 차이가 나타나지 않았다. 그러나 xanthine oxidase 활성은 2% 및 4% 홍국첨가 식이군이 대조군에 비해서 각각 29%, 36% 증가되었으며 2군간에는 의의있는 차이는 없었다. 유해산소 해독에 관여하는 glutathione-5-transferase와 glutathion peroxidase 활성은 2% 및 4% 홍국 첨가식이군 모두 대조군에 비해서 각각 1.1%, 23%의 유사한 증가를 보였으며, 특히 Catalase의 활성은 2%및 4% 홍국 첨가식이군이 대조군에 비해서 각각 41%, 25%의 유의한 (p<0.05) 증가를 보였다. 그리고 superoxide dismutase의 활성과 간조직 glutathione의 함량은 2% 및 4% 홍국 첨가식이군이 대조군에 비해서 높게 나타나는 경향을 보였으며, 2% 흥국 첨가식이군이 4% 홍국 첨가식이군보다 약간 높게 나타났다. 한편 혈청 중 HDL-cholesterol은 2% 및 4% 홍국 첨가식이군이 대조군에 비해서 16% 및 8%높게 나타나는 반면, LDL-cholesterol은 대조군에 비해서 다같이 약 26% 정도 감소되는 경향을 보였고, triglyceride의 함량 역 시 2% 및 4% 홍국 첨가식이군이 대조군에 비해서 모두 약 25% 정도 감소되는 경향을 보였다. 이때 동맥경화지수는 2$^{\circ}C$ 및 4% 홍국 첨가식이군이 대조군에 비해서 각각 39%, 29%의 유의한(P<0.05) 감소를 보였으며, 2% 홍국 첨가식이군 4% 홍국 첨가식이군보다 감소의 정도가 크게 나타나는 경향을 보였다. 이상 실험결과를 종합해 볼 때 홍국 성분은 oxygen free radical의 일종인 $H_2O$$_2$를 제거하는 효소인 catalase의 활성을 증가시킴으로서 유해산소에 의한 동맥경화증의 발생을 예방시켜 줄 수 있을 것으로 사료되나 이점에 대해서는 추후 계속적인 연구 검토가 행해져야할 것으로 생각된다.

• 약학회지
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• 제52권4호
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• pp.316-321
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• 2008

The hepatoprotection by the methanol extract of Oenanthe javanica DC (water dropwort) (OJME) was investigated in Sprague Dawley rats with inducing liver damage by acetaminophen. After OJME administration for 1 week, the increase of hepatic lipid peroxide level by acetaminophen-induced hepatotoxicity was significantly reduced. In case of phase I microsomal enzyme systems including cytochrome P-450, aminopyrine N-demethylase and aniline hydroxylase, any significant differences between in control and in OJME-pretreated group was observed after acetaminophen treatment. However, the pretreatment of OJME maintained the hepatic glutathione level and the activity of liver cytosolic glutathione S-transferase, which was significantly decreased by the acetaminophen intoxication. Among the glutathione-generating system, glutathione reductase was more responsible for its biosynthesis rather than ${\gamma}-glutamylcystein$ synthetase. OJME itself showed the strong inhibition activity on DPPH radical generation. In conclusion, OJME administration maintains the liver glutathione pool and hepatic glutathione S-transferase activity, in addition with its high anti-oxidative capability, to show hepatoprotective effect from acetaminophen intoxication.