• Natural Product Sciences
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• v.10 no.4
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• pp.182-189
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• 2004

To find the action mechanism of the MeOH extract (LFS) of Ligularia fischeri var. spiciformis herbs (Compositae) and its active component, 3,4-dicaffeoylquinic acid (DCQA) on antihepatotoxicity, the effect was investigated on hepatic lipid perxodation and drug-metabolizing enzyme activities in acetaminophen-treated rat. Pretreatment with 250 mg/kg LFS (p.o.) and 10 mg/kg DCQA (p.o.) significantly decreased hepatic lipid peroxidation caused by acetaminophen injection. Further, LFS and DCQA inhibited hepatic microsomal enzyme activation such as hepatic P-450 cytochrome $b_5$, aniline hydroxylase and aminopyrine N-demethylase, suggesting that the two substances might effectively prevent the metabolic activation or scavenge electrophilic intermediates capable of causing hepatotoxicity. Both LFS and DCQA increased hepatic glutathione content and glutathione reductase activity, indicating that both resultantly prevented hepatotoxicity via antioxidative mechanism. Therefore, it was found that LFS had antihepatotoxicity based on the antioxidative action of DCQA.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.6
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• pp.965-972
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• 2004

In the present study, it is observed that Monascus diet may have a hepatoprotective effect on the liver damage induced by bromobenzene in rats. By treatment with bromobenzene (400 mg/kg, i.p.) once a day for 3 consecutive days, the liver damage was reduced in rats fed 2% Monascus diet, based on the liver functional and histopathological findings. Furthermore, retreatment of bromobenzene to the animals with damaged liver showed higher decreasing rate of hepatic glutathione content and increasing rate of cytochrome P450 dependent aniline hydroxylase activity at 4 h in rats fed 2% Monascus diet than those fed STD diet, and V$_{max}$ in glutathione S-transferase was higher in liver of rats fed 2% Monascus diet than those fed STD diet. On the other hand, activities of antioxidant enzymes such as hepatic glutathione S-transferase, catalase and superoxide dismutase were generally higher both in bromobenzene and 2% Monascus diet treated group than those fed STD diet. In conclusion, the rats fed 2% Monascus diet showed lower liver damage than those fed STD diet, which may be due to the acceleration of bromobenzene metabolism and detoxication of oxygen free radicals.s.

• YAKHAK HOEJI
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• v.44 no.6
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• pp.552-557
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• 2000

In order to investigate the effects of Yukmijihwang-Tang on the hepatic microsomal function of Cd-poisoned rats, 3 mg/kg of cadmium (Cd) and 500 mg/kg of Yukmijihwang-Tang extract (YJT), a herbal hepatoprotective medicine, were administered concurrently to rats for 4 weeks. The levels of protein, aniline hydroxylase (AH) and malondialdehyde (MDA) were increased in Cd-treated group. This increase was suppressed by treatment or YJT. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose-6-phosphatase (G-6-P) and ${\delta}-aminolevulinic$ acid dehydratase (ALAD) of Cd-treated group were decreased. This decrease was inhibited by treatment of YJT. Treatment with YJT significantly protects cadmium-induced hepatotoxicity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.22 no.4
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• pp.392-397
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• 1993

The present work was undertaken to investigate the protective mechanism of Oenanthe iavanicu n-butanol extract on the carbon tetrachloride-induced hepatotoxicity in mice. It was observed that a striking enhancement of serum alanine aminotransferase and hepatic lipid peroxide content after carbon tetrachloride administration were markedly decreased by the presentment of Oenanthe javanica extract for 5 days. It was also observed that the hepatic aniline hydroxylase, catalase, glutathione S-transferase activity and glutathione content were not changed by the injection of Oenanthe javanica extract for 5 days. Whereas, hepatic xanthine oxidase activity was inhibited by the treatment of Oenanthe javanica extract for 5 days. After treatment with Oenanthe javanica extract, xanthine oxidase activity was decreased with dose and time-dependent manner as compared to control group. However, hepatic xanthine oxidase activity was not affected by the addition of Oenanthe javanica extract in vitro. These results suggest that the inhibition of hepatic xanthine oxidase activity by the injection of Oenanthe javanica extract is believed to be a possible protective mechanism for the carbon tetrachloride-indured hepatotoxicity in mice.

• Korean Journal of Pharmacognosy
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• v.28 no.2
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• pp.88-92
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• 1997

The full NMR assignment of hispidulin 7-0-neohesperidoside (1) isolated from Cirsium japonicum var. ussuriense was made with the aid of 2D correlation NMR techniques such as HMQC and HMBC. To investigate detoxification of bromobenzene-induced hepatic lipid peroxidation by compound 1, hepatic lipid peroxide level and the activities of enzymes responsible for production and removal of epoxide were studied. The level of lipid peroxide elevated by bromobenzene was significantly reduced by compound 1. This compound administered daily over one week before intoxication with bromobenzene did not affect the activities of aminopyrine N-demethylase, aniline hydroxylase, glutathione S-transferase. Epoxide hydrolase activity was decreased significantly by bromobenzene, which was restored to the control level by pretreatment of persicarin. The results suggest that the bromobenzene-induced hepatic lipid peroxidation by compound 1 is reduced by enhancing the activity of epoxide hydrolase, an enzyme removing bromobenzene epoxide.

• Biomedical Science Letters
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• v.11 no.4
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• pp.509-515
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• 2005

This study was conducted to determine the kinetics of cyclohexane metabolites (the biomarker on cyclohexane exposure), the changes of hepatic cyclohexane metabolizing enzyme activities and the metabolites of cyclohexane in urine or serum. The rats were sacrificed at 2, 4, 8, 12 and 24 hr after administration of one dose of cyclohexane (1.56 g/kg body weight, i.p.). The metabolites of cyclohexane in urine were identified as cyclohexanol, cyclohexanone, trans-l,2-cyclohexanediol and 1,4-cyclohexanediol with cyclohexane metabolite being 124.00, 0.78, 23.28 and 2.75 (g/g of creatinine, $1\times10^{-3}$). Most of the cyclohexanol and trans-l,2-cyclohexanediol were determined to be in the form of $\beta-glucuronide$ conjugates, whereas cyclohexanone and 1 ,4-cyclohexanediol were found as free forms. In toxicokinetics of serum cyclohexane metabolites, cyclohexanol showed a rapid increase, reaching the plateau at 4 hr, after this time rapidly decreased throughout 24 hr. Changes of cyclohexanone also showed the similar pattern with cyclohexanol except somewhat lower concentration. Trans-l,2-cyclohexanediol, however, showed a gradual increase until 12 hr with the continued same levels throughout 24 hr. On the other hand, 1,4-cyclohexanediol was detected as trace levels at 4 and 12 hr, respectively. The administration of cyclohexane led to a significant increase of hepatic aniline hydroxylase activity from 2 to 8 hr. The activity of hepatic alcohol dehydrogenase showed a significant increase at 4 hr and then were recovered to the level of the control at 24 hr. On the other hand, there were no differences in liver weightlbody weight between the control and cyclohexane-treated animals. However, there were the changes of aniline hydroxylase and alcohol dehydrogenase activities on time-dependent pattern after cyclohexane treatment, which influence on the degree of cyclohexane metabolites both in blood and urine. These results suggest that differential determination of cyclohexane metabolites in urine and serum may be able to be as a biomarker of cyclohexane-exposure in the body. But in this fields further study is needed.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.940-945
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• 2002

The present study was done to determine the effect of trolox C, a hydrophilic analogue of vitamin E, on hepatic injury, especially the alteration in cytochrome P-450 (CYP)-dependent drug metabolism during ischemia and reperfusion (I/R). Rats were subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Rats were treated intravenously with trolox C (2.5 mg/kg) or vehicle (PBS, pH 7.4), 5 min before reperfusion. Serum alanine aminotransferase and lipid peroxidation levels were markedly increased after I/R. This increase was significantly suppressed by trolox C. Cytochrome P-450 content was decreased after I/R but was restored by trolox C. There were no significant differences in ethoxyresorufin O-dealkylase (CYP 1A1) and methoxyresorufin O-dealkylase (CYP 1A2) activities among any of the experimental groups. Pentoxyresorufin O-dealkylase (CYP 2B1) activity was decreased and aniline p-hydroxylase (CYP 2E1) activity was increased after I/R. Both these changes were prevented by trolox C. Our findings suggest that trolox C reduces hepatocellular damage as indicated by abnormalities in microsomal drug-metabolizing function during I/R, and that this protection is, in part, caused by decreased lipid peroxidation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.23 no.6
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• pp.894-898
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• 1994

To evaluate an effect of dietary protein on the liver damage, the bromobenzene was intraperitoneally injected to the rats fed a low or high protein diet and then the liver weight per body weight and serum levels of alanine aminotransferase (ALT) activities were determined to demonstrate the differences in liver damage between the groups fed low or high protein diet. Hepatic aniline hydroxylase (AH), glutthione (GSH) content and glutathione s-transferase(GST) activity were also determined to clarify causes of liver damage between the two groups. Increases of liver weight per body weight and serum ALT activities were higher in brombenzene treated rats fed low protein diet than those fed high protein diet. The increasing rate of hepatic AH activity was higher in bromobenzne-treated rats fed low protein diet than that in those fed high protein diet. Furthermore , hepatic glutathione contents and GST activities in bromobenzene-treated rats were higher in rats fed high protein diet than those fed low protein diet. In case of control group, the heaptic glutathione content and GST activity were also higher in rats fed high protein diet than those fed low protein diet.

• Journal of the Korean Society of Food Science and Nutrition
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• v.28 no.1
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• pp.212-217
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• 1999

The effects of nuruk and wheat bran on cholesterol level in serum and activities of free radical metabolizing enzymes were investigated in rats. The rats were fed a diet containing nuruk or wheat bran for one month. Body weight and food intake were measured. Animals were sacrificed after one month. The increased food efficiency ratio throughout whole growth period was observed in the rats fed with either nuruk containing Aspergillus terreus or wheat bran compared with control group on normal diet. In the rats fed with nuruk, hepatic GSH content, glutathione S transferase activity, hepatic cytochrome P 450 content, and aniline hydroxylase activities were generally increased. In the rats fed with nuruk containing other fungi except Aspergillus terreus, xanthine oxidase activity was decreased. The decreased cholesterol level in serum was observed in rats fed with nuruk prepared from Aspergillus terreus and wheat bran. LDL cholesterol level was decreased in rats fed with nuruk prepared with other fungi such as Penicillium sp. and Rhizopus sp. But HDL cholesterol level was increased in all groups fed with nuruk from any fungi and wheat bran. These results suggested that nuruk or wheat bran supplemented diet might exert their effect by decreasing cholesterol level in serum and amount of oxygen free radical level.

• Journal of Environmental Health Sciences
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• v.19 no.3
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• pp.58-63
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• 1993

In order to elucidate the alteration of drug-metabolizing enzymes and mechanism in the animal with hepatic injury and ketosis, the regulation of P450IIE was studied in the rats with heaptic injury caused by CCl$_4$ and with ketosis caused by streptozotocin and high-fat diet. P450IIE expression in liver was examined by the combination of enzyme activities, Western immunoblot, and mRNA Northern blot analyses using specific polyclonal antibody and cDNA probe for P450IIE. Enzyme activity and amounts of immunoreactive P450IIE were rapidly decreased in a time-dependent manner after a single dose of CCl$_4$ . However, the decreases in P450IIE enzyme activity and immunoreactive protein by CCl$_4$ were not accompanied by a decline in its mRNA level. The data thus suggested a post-translational reduction of P450IIE by CCl$_4$. The enzyme activities (aniline hydroxylase) in hepatic microsomes were elevated about 2-3-fold by streptozotocin and feeding with a high fat diet. This increases in enzyme activities were also accompanied by 3-fold increases in immunoreactive P450IIE protein and its mRNA. Our data thus indicated that P450IIE induction during the ketosis appears to be due to pretranslational activation.