• Environmental Analysis Health and Toxicology
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• v.13 no.3_4
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• pp.55-61
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• 1998

Glutathione-S-transferases (GSTs) detoxify electrophilic xenobiotics and reactive metabolites. Recently benzene-fused heterocycles have been shown to increase the total amount of hepatic GSTs in rats. Primarily this study aimed to determine the induction of GSTs by benzoazoles (BAs) including benzoxazole (BX), 2-methylbenzoxazole (M-BX), 2,5-dimethyl benzoxazole (D-BX), benzothiazole (BT), aminobenzothiazole (A-BT) and 2-mercaptobenzothiazole (M-BT) in rats. Hepatic cytosol and poly(A)$^+$ mRNA were prepared from rats after oral administration of BX, BT, M-BX, D-BX, A-BT and M-BT for 5 consecutive days at doses of 1 mmol/kg. Western immunoblot and northern blot analysis were conducted with rabbit anti-GST Ya, Yb$_1$, Yb$_2$, Yc antibodies and cDNA probes containing = 500 bps in the specific coding regions of Ya, Yb$_1$, Yb$_2$, Yc$_1$, and Yc$_2$, respectively. All BAs increased the amount of enzymes and mRNA levels of GSTs. BT was the most effective inducer of GSTs among the compounds examined in this study. Although A-BT and M-BT, the derivatives of BT, induced GSTs, these chemicals had lesser effect on induction of GSTs than BT. The derivatives of BX also induced less GSTs than the parent compound and the addition of methyl group to the benzene ring of BX reduced the induction of GSTs. BAs had better inductive effects on the class $\alpha$(Ya, Yc) than class $\mu$ GSTs (Yb$_1$, Yb$_2$). BAs enhanced mRNA levels of GSTs in parallel with the protein levels. These results indicate that 1) most of BAs induced various isozymes of GSTs, 2) the induction of GSTs appears to be correlated with the chemical structure of the derivatives, and 3) the expression of GST by BAs is presumably under the transcriptional regulation.

• Preventive Nutrition and Food Science
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• v.8 no.3
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• pp.239-244
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• 2003

Recently, we reported (J Korean Soc Food Sci Nutr, 31(3): 516-520, 2002) that Semisulcospira libertina (Marsh Snail) pretreatment has a hepatoprotective effect on $CCl_4$-induced liver damage in rats. The purpose of this study was to investigate the possible mechanisms of hepatoprotection by S. libertina (SL) on liver injury induced by acetaminophen (AA). Male ICR mice were pretreated with dehydrated powder of SL once daily for three consecutive days, given a single toxic dose of AA (450 mg/kg) and liver function determined 24 h later. Liver damage was assessed by quantifying serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and sorbitol dehydrogenase (SDH) activities, and by measuring hepatic lipid peroxidation. To confirm possible mechanism(s), the content of hepatic glutathione (GSH) and gene expression of tumor necrosis factor a (TNF $\alpha$) mRNA by reverse transcription-polymerase chain reaction (RTPCR) were also measured. Pretreatment with SL dramatically lowered AA-elevated ALT, AST and SDH activities. SL pretreatment decreased AA-produced lipid peroxidation by 11% and restored the AA-depleted hepatic GSH by 27%. Furthermore, SL markedly suppressed the expression of TNF $\alpha$ mRNA induced by AA. Our findings revealed that the possible hepatoprotective mechanisms of SL could be attributed, at least in part, to the glutathione-mediated detoxification as well as the regulation of TNF $\alpha$ mRNA expression.

• BMB Reports
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• v.40 no.6
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• pp.1039-1049
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• 2007

Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine and blood urea nitrogen were measured in the experimental sera. Intracellular reactive oxygen species production and total antioxidant activity were also determined from acetaminophen and protein treated hepatocytes. Indices of different antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione-S-transferase) as well as lipid peroxidation end-products and glutathione were determined in both liver and kidney homogenates. In addition, Cytochrome P450 activity was also measured from liver microsomes. Finally, histopathological studies were performed from liver sections of control, acetaminophen-treated and protein pre- and post-treated (along with acetaminophen) mice. Administration of acetaminophen increased all the serum markers and creatinine levels in mice sera along with the enhancement of hepatic and renal lipid peroxidation. Besides, application of acetaminophen to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. It also reduced the levels of antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In addition, acetaminophen enhanced the cytochrome P450 activity of liver microsomes. Treatment with the protein significantly reversed these changes to almost normal. Apart from these, histopathological changes also revealed the protective nature of the protein against acetaminophen induced necrotic damage of the liver tissues. Results suggest that the protein protects hepatic and renal tissues against oxidative damages and could be used as an effective protector against acetaminophen induced hepato-nephrotoxicity.

• Archives of Pharmacal Research
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• v.9 no.4
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• pp.205-209
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• 1986

Glutathione s-transferase in thought to play a key role in initiating the detoxication of potential alkylating agents, including pharmacologically active compounds. It is widely accepted that garlic contained allin which is converted to allicin by allinase. Allicin is easily degraded to diallyl disulfide and other components. This report attempted to observe the effect of diallyl disulfide on some biological activities. It was observed that the activity of serum transaminase was not changed by the treatment of diallyl disulfide. The liver cytosolic glutathione s-transferase was significantly increased. where as the microsomal glutathione s-transferase was not increased.

• YAKHAK HOEJI
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• v.35 no.5
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• pp.384-388
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• 1991

To explore the effect of monosodium-L-glutamate(MSG) on CCI$_{4}$-damaged liver in Wister male rat, 5% MSG solution as drink water were administered after S.C. injection of 0.1 mg/kg CC1$_{4}$ twice a week for 4 weeks. After last administration of MSG, heptic glutathione(GSH) dependent system was assayed. It showed that MSG increased significanly hepatic glutathione(GSH) and glutathione peroxidase(GSH$_{px}$), but decreased glutathione-S-transferase(GST) acivity in normal rats. MSG increased significantly the GSH$_{px}$ and GST activities in rats with CCI$_{4}$-induced liver damage. These results indicate that decrease of GSH dependent systems in CC1$_{4}$ liver injury might be partially elevated by coadministration of MSG.

• Preventive Nutrition and Food Science
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• v.5 no.3
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• pp.126-130
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• 2000

To enhance the antitumor activity of Chinese cabbage kimchi, four kinds of kimchi, which ere differently prepared in kinds and levels of sub-ingredients, were fermented at 15$^{\circ}C$ for 1 day and then at 5$^{\circ}C$ up to pH 4.3. The solid tumor formation, hepatic glutathione S-transferase activity and glutathione contents in the liver, and natural killer (NK) cell activity of spleen were determined from the sarcoma-180 cell injected Balb/c mice that were treated with methanol extracts of the kimchi samples. Kimchi IV, prepared with organically cultivated Chinese cabbage, red pepper powder, garlic, Chinese pepper powder mustard leaf and heat processed salt (Gueun salt), reduced the tumor formation by 39.3% compared to the sarcoma-180 cell treated group, resulting in the smallest tumor weight. Methanol extracts of the kimchi III and kimchi IV recovered the activities of hepatic glutathione S-transferase(GST) that was decreased by the transplantation of the sarcoma-180 cells to th mice. The injections of methanol extracts of kimchi II and kimchi IV increased glutathione contents in sarcoma-180 cells treated mice. The methanol extract of kimchi IV increased the natural killer (NK) cell activity of spleen lymphocytes a more effectively (p<0.05) than those the other kimchi samples. These results suggest that the anticancer activities of kimchi can be increased by changing the kinds and levels of sub-ingredients.

• The Korean Journal of Food And Nutrition
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• v.11 no.1
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• pp.114-122
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• 1998

This study was designed to observe the effect of hot water soluble polysaccharides extract(PS) from Lentinus edodes on the enzyme activities related with hepatic function and peroxidation in the rats fed better yellow. The four groups of male SD rats were fed with the diets contained 15% casein(basal diet; NO group), added butter yellow(BO group) or /and PS(NP, BP group) for 6 weeks. The activities of ${\gamma}$-GTP and GPT in BP were significantly lower compared with BO. The activities of glutathione peroxidase, catalase and lactate dehydrogenase were not significantly different between NP and NO, while those activities were significantly lower value in BP than BO. The activities of glutathione S-transferase of the microsomal and cytosol fractions were significantly lower in BP than in BO. The contents of glutathione and malondialdehyde in the liver were considerably low value in BP. In a view of these results the PS of Lentinus edodes prevents the lipid peroxidation and diminishes the liver toxicity caused with better yellow. The superoxide dismutase activity in cytosolic fraction of liver was not found any effect in all groups. But hepatic function enzyme activities such as catalase and glutathione peroxidase, LDH activities were remarkably decreased in the groups 2(basal diet + PS) and the ${\gamma}$-GTP, GOT and GPT activities, too. In liver, the contents of glutathione decreased by PS supplementation but HDL-cholesterol and total cholesterol ratio in plasma decreased at the groups 3, 4. The ${\gamma}$-GTP, GOT and GPT in plasma were remarkably higher in the rats fed the p-DAB than the control group, too. But above enzyme activities significantly decreased in the groups fed PS.

• 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.

• Journal of Nutrition and Health
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• v.42 no.5
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• pp.415-422
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• 2009

The present study was conducted to investigate the effect of dietary supplementation of grape pomace on lipid peroxidation and related enzyme activities of rats fed high fat diet. Male Sprague-Dawley rats weighing about 90 g were assigned to 4 experimental groups of 8 rats on the basis of their body weight. The high fat diet contained additional 15% lard to AIN 93-based diet. Rats were fed experimental diets containing 5% grape pomace for 4 weeks. Dietary supplementation of grape pomace reduced serum concentration of lipid peroxide in rats fed high fat diet. Hepatic concentration of lipid peroxide tended to be lower by feeding grape pomace. Hepatic total glutathione content and GSH/GSSG ratio were increased by grape pomace feeding in normal or high fat diet groups. Hepatic superoxide dismutase activity of grape pomace group with high fat diet was induced significantly compared with high fat diet group without grape pomace. Hepatic catalase activity of high fat fed rats was induced by feeding grape pomace. Grape pomace diet increased glutathione-S-transferase and glutathione peroxidase activities in rat liver fed high fat. Hepatic glucose-6-phosphatase activity was not affected by dietary supplementation of grape pomace in rats fed high fat. These results suggest that dietary supplementation of grape pomace may alleviate lipid peroxidation through antioxidant effect in rats fed high fat.

• Journal of Nutrition and Health
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• v.36 no.8
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• pp.793-800
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• 2003

This study was conducted to investigate the antioxidative effects of Paeonia lactiflora (PL) seeds on antioxidative defense system and lipid peroxidation of liver in rats fed high-cholesterol diet. Sprague-Dawley male rats weighing 100 $\pm$10g were randomly assigned into five experimental groups fed 0.5% cholesterol ; HC group which was not supplemented PL seeds extract, 0.1% methanol extract diet group (MP1 group), 0.2% methanol extract diet group (MP2 group), 0.05% ether-souble fraction diet group (EP1 group) and 0.1 % ether-souble fraction diet group (EP2 group). Experimental diets were fed ad libitum to the rats for 3 weeks. The activity of hepatic superoxide dismutase (SOD) was not significantly different among all the high cholesterol diet groups. The hepatic glutathione peroxidase (GSHpx) activity in MP2 group was increased to 27% compared to HC group. The activity of hepatic catalase (CAT) was not significantly different among the all high cholesterol diet groups. The hepatic glutathione S-transferase (GST) activity in the EP1 and EP2 groups were increased to 12% and 13%, respectively, as compared to HC group. The levels of hepatic TBARS in the MP1, MP2, EP1 and EP2 groups were reduced by 18%, 21%, 20% and 23%, respectively, as compared with HC group. The contents of lipofuscin in liver was not significantly different among all the experimental groups. The results indicated that PL seeds extract may be reduced oxidative damage by activating antioxidative defense system of hepatic in rats fed high-cholesterol diets. (Korean J Nutrition 36(8): 793∼800, 2003)