• YAKHAK HOEJI
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• v.28 no.1
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• pp.29-33
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• 1984

The paper aimed to review the influences of ginseng on the metabolism of foreign substances and on the activity of hepatic drug metabolizing enzyme system in mouse or rat liver. It has been known that ginseng components reduces the motality rates and the toxic effects induced by foreign materials. Chronic pretreatment of mouse or rat with ginseng extract fractions or saponin caused the increase in the metabolism of foreign materials and the activity of drug metabolizing enzymes, such as cytochrome $P_{450}$, NADPH cytochrome C reductase and glucuronyl S-transferase in liver. Thus, it may be concluded that decrease in toxic effect of foreign substances by ginseng pretreatment may be partly related to the induction of drug metabolizing enzymes in liver.

• Archives of Pharmacal Research
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• v.9 no.2
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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.

• YAKHAK HOEJI
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• v.44 no.3
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• pp.237-244
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• 2000

Liver isolated from 18 hours fasted rats was subjected to $N_2$hypoxia (for 45 min) followed by reoxygenation (for 30 min). The perfusion medium used was Krebs-Henseleit bicarbonate buffer (pH 7.4, $37^{\circ}C$). Vitamin C (0.5 mM) and trolox C (0.5 mM), soluble vitamin E analog, were added to perfusate. Lactate dehydrogenase (LDH), total glutathione, oxidized glutathione, lipid peroxide and drug-metabolizing enzymes were measured. After hypoxia LDH significantly increased but this increase was attenuated by vitamin C and combination of vitamin C and E. Total glutathione and oxidized glutathione in perfusate markedly increased during hypoxia and this increase was inhibited by vitamins C, E and its combination. Similarly; oxidized glutathione and lipid peroxide in liver tissue increased after hypoxia and reoxygenation and this increase was inhibited by vitamin I and combination of vitamin C and E. Hepatic drug metabolizing function (phase I, II) were suppressed during hypoxia but improved during reoxygenation. While vitamins C and E only increased glucuronidation, the combination of vitamin C and E increased the oxidation, glucuronidation and sulfation. Our findings suggest that vitamins C and E synergistically ameliorates hepatocellular damage as indicated by abnormalities in drug metabolizing function during hypoxia/reoxygenation and that this protection is in major part, caused by decreased oxidative stress.

• Biomolecules & Therapeutics
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• v.12 no.3
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• pp.185-188
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• 2004

The purpose of this study is to evaluate the effect of cigarette smoke condensate (CSC) on toxification/detoxification metabolic pathway in primary cultured rat hepatocytes. We measured the activities of cytochrome P450 monooxygenases (CYP450s) and UDP-glucuronyltransferase, sulfotransferase and glutathione-S-transferase in CSC-treated rat hepatocytes. CSC significantly increased the activities of hepatic CYP4501A1 and CYP4501A2 to 7.5 fold and 1.6 fold respectively, compared with control level. However, CSC did not affect the activities of conjugation enzymes. We a1so examined if treatment of CSC could change thc cytotoxicity of acetaminophen (AA) through modulation of metabolizing enzymes. In rat hepatocytes, pretreatment with CSC potentiated the cytotoxicity of AA. This result indicates that potentiation of AA toxicity by CSC pretreatment may be related to induction of CYP4501A1 and CYP4501A2.

• Archives of Pharmacal Research
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• v.13 no.3
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• pp.265-268
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• 1990

The effects of lignans, related to macelignan, on hepatic microsomal drug-metabolizing enzyme (DME) activity were evaluated to elucidate the structure-activity relationship in mice and rats. The compounds carrying the methylenedioxyphenyl nucleus were found to be the msot potent among compounds tested; which not only produced a marked inhibition of DME with a single dose but a significant induction with repeated treatments. Lack of the methylenedioxy group caused marked decrease in the activity, implying that a methylenedioxy group is essential and of major importance eliciting DME modifying activity.

• Advances in Traditional Medicine
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• v.7 no.3
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• pp.311-320
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• 2007

The present study was designed to estimate the protective effect of (-) epigallocatechin gallate (EGCG) on ethanol-induced liver injury in rats. Chronic ethanol administration (6 g/kg/day ${\times}$ 60 days) caused liver damage that was manifested by the elevation of markers of liver dysfunction - aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, bilirubin and ${\gamma}$-glutamyl transferase in plasma and reduction in liver glycogen. The activities of alcohol metabolizing enzymes such as alcohol dehydrogenase and aldehyde dehydrogenase were found to be altered in alcohol-treated group. Ethanol administration resulted in the induction of cytochrome p450 and cytochrome-$b_{5}$ activities and reduction of cytochrome-c reductase and glutathione-S-transferase, a phase II drug metabolizing enzyme. Further, ethanol reduced the viability of isolated hepatocytes (ex vivo) as assessed by trypan blue exclusion test and induced hepatocyte apoptosis as assessed by propidium iodide staining. Treatment of alcoholic rats with EGCG restored the levels of markers of liver injury and mitigated the alterations in alcohol metabolizing and drug metabolizing enzymes and cyt-c-reductase. Increased hepatocyte viability and reduced apoptotic nuclei were observed in alcohol + EGCG-treated rats. These findings suggest that EGCG acts as a hepatoprotective agent against alcoholic liver injury.

• Natural Product Sciences
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• v.18 no.2
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• pp.121-129
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• 2012

Hepatoprotective effects of methanol extract and alisol B 23-acetate of Alisma orientale were studied in acetaminophen (APAP)-treated rats. APAP increased hepatic content of lipid peroxide, which was suppressed by methanol extract and alisol B 23-acetate. The liver of rats treated with APAP had higher P-450, aminopyrine N-demethylase and aniline hydroxylase activities than those of normal control rats. The increases in hepatic drug metabolizing enzymes by the i.p. injection of APAP were significantly alleviated by the administration of methanol extract or alisol B 23-acetate. The injection of APAP also resulted in a substantial reduction of hepatic glutathione content and glutathione S-transferase activity, and the decreases were partially, but significantly, restrained by the oral administration of methanol extract prior to the i.p. injection of APAP. Hepatic activities of glutathione reductase (GR) and ${\gamma}$-glutamylcystein synthetase ${\gamma}$-GCS) were also decreased significantly in APAP-treated rats. The decreases in hepatic GR and ${\gamma}$-GCS activities by APAP injection were improved partially, but significantly, with administration of methanol extract of A. orientale. Treatment with alisol B 23-acetate also improved the hepatic ${\gamma}$-GCS activity significantly, but not GR.

• Food Science and Biotechnology
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• v.16 no.3
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• pp.439-443
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• 2007

The effects of the methanol extract of the leaves of Brassica juncea and isorhamnetin $3-O-{\beta}-D-glucopyranoside$, major compound isolated from the ethyl acetate fraction of this plant on hepatic lipid peroxidation and drug-metabolizing enzymes, were evaluated in rats treated with bromobenzene. The extract and isorhamnetin $3-O-{\beta}-D-glucopyranoside$ of oral administration did not show any significant effects on activities of aminopyrine N-demethylase and aniline hydroxylase, enzymes forming toxic epoxide by bromobenzene as well as on glutathione content. However, both methanol extract and isorhamnetin $3-O-{\beta}-D-glucopyranoside$ significantly recovered the decreased activities of glutathione s-transferase and epoxide hydrolase, and also reduced the lipid peroxide level in rats treated with bromobenzene. From the results, the protections of this plant against bromobenzene-induced hepatotoxicity are thought to be via enhancing the activities of epoxide hydrolase and glutathione s-transferase, enzymes removing toxic epoxide, and reducing the lipid peroxide level.

• Korean Journal of Pharmacognosy
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• v.27 no.4
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• pp.323-327
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• 1996

The ether soluble fraction of the roots of Angelicae gigantis Radix caused a significant prolongation of hexobarbital(HB) induced sleeping time in mice. Through systematic fractionation of the ether fraction monitored by bioassays, two pyranocoumarins, decursinol angelate and decursin were isolated as active principles. Decursin, as a main component, exhibited significant prolongation of HB-induced hypnosis as well as significant inhibition of hepatic microsomal drug metabolizing enzyme(DME) activities at relatively high dose which indicated that it is a weak DME inhibitor.

• Environmental Analysis Health and Toxicology
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• v.18 no.2
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• pp.69-76
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• 2003

Effects of ambient nitrite, NO$_2$$\^$-/, at 1, 3, 10 and 30 mg/1, on the changes of plasma nitrite/nitrate and on hepatic drug - metabolizing enzyme activity were examined in the juvenile Israeli carp, Cyprinus carpio. When the fish were exposed to 1 and 3 mg/1 NO$_2$$\^$-/, there was an exposure duration-dependent increase in plasma NO$_2$$\^$-/ over the 96-hr period reaching 6∼7 fold excess the ambient concentration. In the fish exposed to 10 mg/1, a plateau concentration of less than 2-fold of the environment was attained in 12 hr. With 30 mg/1, however, the maximal plasma NO$_2$$\^$-/ was 41.25 mg/1 at 12 hr followed by a gradual decline. There was a concentration-dependent increase in methemoglobin (metHb) level in all NO$_2$$\^$-/ -exposed groups and a significant decrease in hematocrit value in 30 mg/l group after 96-hr exposure. Apart from the blunted increase in plasma NO$_2$$\^$-/ with higher NO$_2$$\^$-/ (10 and 30 mg/1) exposure, the ratio of plasma NO$_3$$\^$-/ to NO$_2$$\^$-/ was signifirantly higher in these groups compared to 1 and 3 mg/1. The imbalance in the plasma NO$_3$$\^$-//NO$_2$$\^$-/ at higher NO$_2$$\^$-/ exposure suggests a possible accelerated conversion of NO$_2$$\^$-/ to NO$_3$$\^$-/. Nitrite exposure did not affect the hepatic drug-metabolic activities in juvenile Israeli carp. All these data indicate that disposition of NO$_2$- differ depending upon exposed concentration and that metHb production may not be the exclusive toxic mechanism in carp.