• Title/Summary/Keyword: aminopyrine N-demethylase

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The Roles of Kupffer Cells in Hepatic Dysfunction Induced by Ischemia/Reperfusion in Rats

  • Jung Joo-Yeon;Lee Sun-Mee
    • Archives of Pharmacal Research
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    • v.28 no.12
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    • pp.1386-1391
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    • 2005
  • This study examined the role of Kupffer cells in altering the hepatic secretory and microsomal function during ischemia and reperfusion (ls/Rp). Rats were subjected to 60 min of hepatic ischemia, followed by 1 and 5 h of reperfusion. Gadolinium chloride ($GdCl_{3}$, 7.5 mg/kg body weight, intravenously) was used to inactivate the Kupffer cells 1 day prior to ischemia. Is/Rp markedly increased the serum aminotransferase level and the extent of lipid peroxidation. $GdCl_{3}$ significantly attenuated these increases. Is/Rp markedly decreased the bile. flow and cholate output, and $GdCl_{3}$ restored their secretion. The cytochrome P450 content was decreased by Is/Rp. However, these decreases were not prevented by $GdCl_{3}$. The aminopyrine N-demethylase activity was decreased by Is/Rp, while the aniline p-hydroxylase activity was increased. $GdCl_{3}$ prevented the increase in the aniline p-hydroxylase activity. Overall, Is/Rp diminishes the hepatic secretory and microsomal drug-metabolizing functions, and Kupffer cells are involved in this hepatobiliary dysfunction.

Effects of Dandelion on Oxygen Free Radical Generating and Scavenging System of Brain in Streptozotocin-Induced Diabetic Rats (서양민들레가 Streptozotocin으로 유발한 당뇨 횐쥐의 뇌조직 중 유해 활성산소 생성 및 제거 효소계에 미치는 영향)

  • 김명주;조수열
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.3
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    • pp.500-505
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    • 2002
  • Many studies have shown that hyperglycemia leads to an increase of lipid peroxidation in diabetic patients and animals, reflecting a rise reactive oxygen species production. It is increasingly recognized that brain is another site of diabetic organ damage. Accordingly, this study was to investigate the effect of dandelion on oxygen free radical generating and scavenging system of brain in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were divided into diabetic (control) and diabetic-dandelion supplemented groups. Dandelion was supplemented for 4 weeks with dandelion leaf and root powder (DLP, DRP) or dandelion leaf and root water extract (DLW, DRW) based on 11.4 g of raw dandelion/kg diet. Diabetes was induced by single injection STZ (55 mg/kg B.W., i.p.)in a citrate buffer. Oxygen free radical generating enzymes, cytochrome P-450, amino-pyrine N-demethylase, aniline hydroxylase and xanthine oxidase, were lowered in dandelion supplemented-groups compared to the control group. Superoxide dismutase, catalase and gluthathione peroxidase activities of brain were also lower in dandelion leaf and root supplemented-group than in the control group, whereas glutathione S-transferase activity and gluthathione content were increased in dandelion supplemented-groups compared to the control group. With regard to the lipid peroxidation products, the malondialdehyde content of brain was lower in dandelion supplemented groups. Therefore, it could be suggested that powder and water extract of dandelion leaf or root are beneficial in preventing diabetic complication from lipid peroxidation and free radical in brain of diabetic rat brain.

The Anti-hepatotoxic Effect of Ginseng in Rats: Meta-analysis

  • Kook, Se-Jeong;Han, Hye-Kyoung;Kim, Gun-Hee;Choi, Ki-Heon
    • Journal of the Korean Data and Information Science Society
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    • v.19 no.3
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    • pp.937-949
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    • 2008
  • The purpose of this meta-analysis was to investigate the anti-hepatotoxic effect of ginseng in rats induced with CC14 or TCDD, the toxicities that cause liver damages. Primary studies were collected from the ScienceDirect database, the DBpia, and the KISS. The data on the effect factors in plasma and in enzyme are listed as many as possible: The effect factors were alanine transaminase(ALT), aspartate transaminase(AST), liver aminopyrine N-demethylase(AD), liver aniline hydroxylase(AH), liver 3,4-Methylenedioxyamphetamine(liver MDA), cytochrome P450(P450), serum alkaline phosphatase(ALP), serum lactate dehydrogenase(LDH), cytochrome b5(Cyto b5), glutathione reductase (GR), Liver glutathione S-transferase(GST), liver glutamyltransferase (GT), Liver($\gamma$-GCS), serum liver 3,4-Methylenedioxyamphetamine(serum MDA), serum sorbitol dehydrogenase(SDH), serum total protein(TP), and serum $\gamma$-glutamyltransferase($\gamma$-GT). In order to investigate the effect of ginseng, the standard mean difference(HG) between the group of rats induced with toxicity(RH) and the group of rats induced with ginseng(RHG) were combined, and the significance of HGs were tested. The combined HGs checked the biases caused by heterogeneity among studies and the publication biases. Then they were adjusted by using the random effect model and trim and fill method. Although the publication biases were assumed, among all plasma factors the HGs of ALT, AST, serum MDA, SDH, TP, and $\gamma$-GT were significant, and among all enzyme factors the HGs of liver MDA, Cyto b5, GR, GST, and GT were significant. The treatment with ginseng significantly affected the plasma and enzyme levels in rats induced with toxicity.

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INDUCTION OF CYTOCHROME P-450 ASSOCIATED MONOOXYGENASE ACTIVITIES BY PHENOBARBITAL AND 3-METHYLCHOLANTHRENE IN PRIMARY CULTURES OF ADULT RAT HEPATOCYTES

  • Park, Seong-Kyu;Ha, Jong-Ryul;Kim, H.M.;Yang, K.H.
    • Toxicological Research
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    • v.3 no.1
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    • pp.1-8
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    • 1987
  • In vitro induction of cytochrome 450 associated monooxygenase activities by phenobarbital (PB) and 3-methylcholanthrene (MC) was investigated in primary cultures of adult rat hepatocytes. PB and MC were added to the culture 24 hr after the initial plating of hepatocytes. A signiftcant increase of the activities of 7-ethoxycoumarin 0-deethylase and aryl hydrocarbon hydroxylase were observed in MC and PB treated culture. MC caused about 500% induction of the initial oxidation rates of both enzymes in 48 hr. However the PB maintained both enzyme activities close to the level of freshly isolated hepatocytes. Biphenyl 4-hydroxylase and aminopyrine N-demethylase activities were also induced by MC and PB. But the level of induction was less than that occuring with 7-ethoxycoumarin 0-deethylase and aryl hydrocarbon hydroxylase. When aflatoxin $B_1$ was added to the hepatocyte cultures which have been treated with MC or PB, it caused a significant increase of the unscheduled DNA synthesis at higher dose of aflatoxin $B_1$ as compared to those of untreated control hepatocyte cultures. The results suggest that microsomal enzyme activities can be selectively controlled preferably in hepatocyte cultures by the in vitro induction method. This principle may be useful for studying the metabolism and other toxicological studies.

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Evaluation of the Efficacy of Kochiae fructus Extract in the Alleviation of Carbon Tetrachloride-induced Hepatotoxicity in Rats

  • Kim Na-Young;Lee Jeong-Sook;Kim Seog-Ji;Park Myoung-Ju;Kim Seok-Hwan
    • Nutritional Sciences
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    • v.8 no.4
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    • pp.212-218
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    • 2005
  • Hepatoprotective effects of the extract of Kochiae fructus (KF), a traditional oriental medicinal plant, were evaluated against carbon tetrachloride($CCl_4$)-induced liver damage in rats. Male Sprague-Dawley rats were divided into control, $CCl_4,\;CCl_4$ plus methanol extract of KF (KFM-$CCl_4$), and $CCl_4$ plus butanol extract of KF (KFB-$CCl_4$) groups. KFM and KFB were orally administered once a day (200 mg/kg body weight) for 14 days. A mixture of 0.2 mL/100 g body weight of $CCl_4$ in olive oil was injected at 30 minutes after the final administration of KFM and KFB. The KFB pretreatment resulted in a significant decrease in the serum transaminase and lactic dehydrogenase levels in the $CCl_4$-treated rats. The $CCl_4$ treatment significantly lowered the activities of glutathione, glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px). However, pretreatment with KFM and KFB resulted in a significant increase in the glutathione, GR and GST levels. KFB increased the activities of SOD, catalase and GSH-Px, but KFM did not alter them. Pretreatment with KFM and KFB resulted in a significant decrease in the production of aminopyrine N-demethylase in the $CCl_4$-treated rats. KF extract would appear to contribute to alleviate the adveISe effect of $CCl_4$ treatment by enhancing the hepatic antioxidant defense system.

Protective Effect of Oenanthe javanica Extract on Acetaminophen-induced Hepatotoxicity in Rats (Acetaminophen으로 유도한 쥐의 간 독성에 대한 미나리(Oenanthe javanica) 추출액의 간 보호 작용)

  • Park, Jong-Cheol;Kim, Jong-Yeon;Lee, Youn-Ju;Lee, Ji-Seon;Kim, Bo-Geum;Lee, Seung-Ho;Nam, Doo-Hyun
    • YAKHAK HOEJI
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    • v.52 no.4
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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.

Potentiation of Carbon Tetrachloride Hepatotoxicity induced by Repeated Physical Exercise in adult Female rats (백서의 반복적인 육체운동에 의한 사염화탄소 간독성의 증폭효과)

  • Kim, Su-Nyeon;Kim, Young-Chul
    • Toxicological Research
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    • v.8 no.2
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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).

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Protective effects of alginate-free residue of sea tangle against hyperlipidemic and oxidant activities in rats

  • Yim, Mi-Jin;Choi, Grace;Lee, Jeong Min;Cho, Soon-Yeong;Lee, Dae-Sung
    • Fisheries and Aquatic Sciences
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    • v.20 no.9
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    • pp.22.1-22.6
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    • 2017
  • The antihyperlipidemic and antioxidant activities of dietary supplementation of sea tangle from Goseong and the alginate-free residue of sea tangle were investigated in Sprague Dawley rats treated with a high-fat diet, streptozotocin, poloxamer 407, and bromobenzene. The alginate-free residue of Goseong sea tangle induced a significant reduction in triglycerides and total cholesterol levels, as well as a significant increase in high-density lipoprotein cholesterol levels. Alginate-free Goseong sea tangle residue reduced the activities of the phase I enzymes aminopyrine N-demethylase and aniline hydroxylase, which had been increased by intraperitoneal injection of bromobenzene. Pretreatment with Goseong sea tangle residue prevented a bromobenzene-induced decrease in epoxide hydrolase activity. Bromobenzene reduced hepatic glutathione content and increased hepatic lipid peroxide levels. Pretreatment with alginate-free Goseong sea tangle residue prevented lipid peroxidation induced by bromobenzene, but pretreatment with Goseong sea tangle did not. These results suggest that Goseong sea tangle residue exerted antihyperlipidemic and antioxidant activities that were higher than those induced by alginate-containing sea tangle. Therefore, the alginate-free residue may contain physiologically unknown active components, other than alginic acid, which may potentially be used to prevent hyperlipidemic atherosclerosis.

Effect of SAENGCHINYANGHYOLTANG on the hepatic metabolic enzyme system in streptozotocin-induced diabetic rats (고혈당(高血糖) 쥐의 간(肝) 대사효소계(代謝酵素系)에 미치는 생진양혈탕(生津養血湯)의 영향(影響))

  • Kim, Shin-Seok;Lee, Kyung-Hee;Lee, Cheol-Whan;Choi, Jong-Won;Kim, Seock-Hwan
    • The Journal of Korean Medicine
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    • v.16 no.2 s.30
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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.

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In vivo and In vitro Anti-lipid Peroxidative Effect of the Extract Complex of Korean Anti-thirst Drugs (한방 소갈약 추출물 및 복합물에 의한 In vivo 및 In vitro 지질과산화 저해효과)

  • 이경태;박동영;박희준;정현주;박건영;최종원
    • YAKHAK HOEJI
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    • v.46 no.5
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    • pp.358-363
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    • 2002
  • In Oriental medicine, the prescriptions composed of several herb medicines have been used. It is still unclear how the sum of several extracts of anti-thirst drugs represents the anti-lipid peroxidative action. Three anti-thirst herb medicines, Kalopanax pictus (K), Pueraria thunbergiana (P) and Rhus verniciflua (R), were extracted with MeOH and $H_2O$, respectively, and the former one was fractionated into the resultant EtOAc extract. Each extract was reconstituted to give KPR311, KPR131 and KPR113 where, for example, KPR311 represents the complex of K-P-R {3:1:1 (w/w/w)} of the three extracts. The order of the inhibitory effect in bromobenzene-induced lipid peroxidation in rats was as follows: EtOAc extract>$H_2O$ extract>MeOH extract. Extract complexes were found to be more potent than the extracts of individual crude drugs. The KPR131 of EtOAc extract was found to be the most potent among the tested samples. These anti-lipid peroxidative effects were also supported by the decrease of aniline hydroxylase activity and aminopyrine N-demethylase activity, on the other hand by the increase of epoxide hydrolase activity. All the tested samples were assayed in vitro antioxidative effects such as DPPH assay, ADP/NADPH/Fe$^{3+}$ assay and ascorbic acid/Fe$^{2+}$ assay. The EtOAc extracts also showed the most significant antioxidative effects. These results suggest that the sum of anti-thirst drugs could reflect the effects of respective crude drugs.s.s.