• Biomedical Science Letters
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• v.5 no.2
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• pp.201-208
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• 1999

To evaluate an effect of growth periods on the bromobenzene-induced liver damage, bromobenzene was administrated to 5-week-old rats and 10-week-old rats pretreated with bromobenzene 5 times every other day for 10 days and then the animals were sacrificed. The results were obtained as follows; The increasing rate of serum levels of alanine aminotransferase, xanthine oxidase activity, hepatic lipid peroxide contents, liver weight per body weight (％) and decreasing rate of hepatic contents of protein to each control group were higher in 10-week-old rats than 5-week-old rats by the pretreatment of bromobenzene. According to the above results, 10-week-old rats indicated more severe liver injury than 5-week-old those in case of bromobenzene pretreatment. On the other hand, hepatic aniline hydroxylase activity was more increased in 10-week-old rats than 5-week-old rats both in control and bromobnezene pretreated rats where as the reverse in hepatic glutathione S-transferase. In case of hepatic GSH determination at the intervals of 2, 4, 8, 24 hours throughout 24 hr after administration of single dose of bromobenzene to 5-week-old and 10-week-old rats both in control and bromobnezene pretreated, the rate of GSH utilization was lower in 10-week-old rats than 5-week-old rats. In conclusion, from the above experimental, it is deduce that the 10-week-old rats showed more severe liver injury than 5-week-old rats by the bromobenzene treatment because the disposal ability of bromobenzene in liver was lower in 10-week-old rats than 5-week-old rats.

• Journal of Nutrition and Health
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• v.44 no.1
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• pp.16-28
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• 2011

Oxidative stress leads to the induction of cellular oxidative damage, which may cause adverse modifications of DNA, proteins, and lipids. The production of reactive species during oxidative stress contributes to the pathogenesis of many diseases. Antioxidant defenses can neutralize reactive oxygen species and protect against oxidative damage. The aim of this study was to assess the antioxidant status and the degree of DNA damage in Korean young adults using glutathione s-transferase (GST) polymorphisms. The GSTM1 and GSTT1 genotypes were characterized in 245 healthy young adults by smoking status, and their oxidative DNA damage in lymphocytes and antioxidant status were assessed by GST genotype. General characteristics were investigated by simple questionnaire. From the blood of the subjects, GST genotypes; degree of DNA damage in lymphocytes; the erythrocyte activities of superoxide dismutase, catalase, and glutathione peroxidase; plasma concentrations of total peroxyl radical-trapping potential (TRAP), vitamin C, ${\alpha}$- and ${\gamma}$-tocopherol, ${\alpha}$- and ${\beta}$-carotene and cryptoxanthin, as well as plasma lipid profiles, conjugated diene (CD), GOT, and GPT were analyzed. Of the 245 subjects studied, 23.2% were GSTM1 wild genotypes and 33.4% were GSTT1 wild genotype. No difference in erythrocyte activities of superoxide dismutase, catalase, or glutathione peroxidase, and the plasma TRAP level, CD, GOT, and GPT levels were observed between smokers and non-smokers categorized by GSTM1 or GSTT1 genotype. Plasma levels of ${\alpha}$- and ${\gamma}$-tocopherol increased significantly in smokers with the GSTT1 wild genotype (p < 0.05); however, plasma level of ${\alpha}$-carotene decreased significantly in non-smokers with the GSTM1 wild genotype (p < 0.05). DNA damage assessed by the Comet assay was significantly higher in non-smokers with the GSTM1 genotype; whereas DNA damage was significantly lower in non-smokers with the GSTT1 genotype. Total cholesterol and LDL cholesterol levels were significantly higher in non-smokers with the GSTT1 genotype than those with the GSTT1 wild genotype (p < 0.05). In conclusion, the GSTM1 genotype or the GSTT1 wild genotype in non-smokers aggravated their antioxidant status through DNA damage of lymphocytes; however, the GSTT1 wild type in non-smokers had normal plasma total cholesterol and LDL-cholesterol levels. This finding confirms that GST polymorphisms could be an important determinant of antioxidant status and plasma lipid profiles in non-smoking young adults. Further study is necessary to clarify the antioxidant status and/or lipid profiles of smokers with the GST polymorphism and to conduct a study with significantly more subjects.

• Korean Journal of Community Nutrition
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• v.4 no.2
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• pp.239-247
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• 1999

Six-week-old Sprague Dawley rats were fed the diets of 20% casein or soy protein. Two weeks after the feeding, hepatocellular chemical carcinogenesis was initiated by diethylnitrosamine(DEN), and promoted by the diet containing 0.01% 2-acetylamino-fluorene(AAF) and two-thirds partial hepatectomy(PH). The animals were sacrificed at 8 weeks after the DEN injection. The area of placetal glutathione S-trnasferase(GST-P) positive foci, the activities of several enzymes in cellualr antioxidant enzyme systems and glucose 6-phosphatase were determined to investigate the mechanism of the anticarcinogenic effect by the dietary proteins. In another set of experiments, the drinking water of rats fed casein was supplemented with 1.5% inositol hexaphosphate(InsP6) to elucidate whether it has the comparable anticancer action of soy protein. The area and number of GST-P positive foci in the soy protein group were significantly(p<0.05) lower than those inthe casein group. The livers of rats fed casein showed moderate fattydegeneration and larger hyperplastic nodules than those of rats fed soy protein. In another set of experiments, the area and number of GST-P positive foci in the rats fed casein supplemented with InsP6 were not significantly different from those in the rats fed casein or soy protein. The lipid peroxidation of rats fed different protein sources showed no significant difference. Glutathione S-transferase(GST) activities were increased significantly(p<0.05) by carcinogen treatment in all dietary groups. Glucose 6-phosphatase(G6Pase) activities were decreased by carcinogen treatment, and hence showed a reverse relationship(r=-0.695, p<0.01) to the GST-P positive foci. Therefore, the activities in the rats fed casein were lower than those in the rats fed soy protein. These results suggest that the soy protein seems to be more anti-carcinogenic than casein by decreasing the preneoplastic lesion and by increasing the membrane stability but inositol hexaphosphate, a component of soy protein, may not be protective against hepatocarcinogenesis.

• BMB Reports
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• v.32 no.3
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• pp.259-265
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• 1999

This study was designed to examine the anticarcinogenic effect of dietary supplementation with garlic powder on rat hepatocarcinogenesis. All rats were initiated by a single dose (200 mg/body weight) intraperitoneal injection of diethylnitrosamine (DEN), and three weeks later, subjected to two-thirds partial hepatectomy. Two weeks after initiation, four groups of rats were given experimental diets supplemented with 0 (control group), 0.5, 2.0, or 5.0% garlic powder for 6 weeks. Rats were sacrificed at eight weeks after initiation. The induction of placental glutathione S-transferase (GST-P) positive foci was significantly inhibited almost equally in all three groups fed garlic diets. Glucose 6-phosphatase (G6Pase) activity was increased in rats fed 0.5% and 2.0% garlic powder, and was negatively correlated with the number and area of GST-P positive foci. Thiobarbituric acid reactive substance (TBARS) contents were decreased in rats fed 2.0% and 5.0% garlic powder. Only 5.0% garlic powder supplementation significantly increased the glutathione content and the glutathione S-transferase activity, compared to the control group. Therefore, all levels of garlic powder, 0.5% to 5.0%, exerted an anti promotional effect during hepatocarcinogenesis. Dietary supplementation with garlic powder seemed to maintain microsomal membrane integrity by increasing G6Pase activities. Glutathione-dependent detoxifying enzymes did not seem to contribute to this protective effect directly. The present study suggests that garlic powder is effective in inhibiting the induction of GST-P positive foci, possibly by stabilizing the hepatic microsomal membrane.

• Journal of Nutrition and Health
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• v.38 no.5
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• pp.364-372
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• 2005

This study is designed to examine the effects of dietary supplementation with vitamin E and dehydroepiandrosterone (DHEA) on the formation of preneoplastic lesions in diethylnitrosamine (DEN) induced rat hepatocarcinogenesis. All Weaning male Sprague-Dawley rats were initiated by a single dose of DEN (200mg/kg body weight), subjected to two­thirds partial hepatectomy 3 weeks later and were sacrificed 8 weeks after DEN initiation. Two weeks after initiation, rats were fed Purina purified rodent diet 5053 (Ralston Purina Rat chow, USA) with $1.5\%$ (15,000 IU/kg diet) vitamin E, $0.5\%$ DHEA and both of those supplemented diet for 6 weeks. Placental glutathione S-transferase (GST-P) positive foci, the activities of catalase, total-glutathione peroxidase (GPx) , glutathione reductase (GR), glutathione S-transferase (GST) and thiobarbituric acid reactive substances (TBARS) contents were decreased significantly by vitaimin E supplement. On the other hand GST-P positive foci number, Cu/Zn-superoxide dismutase (SOD) and glucose 6-phosphatase (G6Pase) activities weren't changed by vitamin E supplement. It might suggest that protective effect of vitamin E against hepatocarcinogens is not involved in the formation of the GST-P positive foci but related to the expansion of that. It seemed that vitamin E supplement helped endogenous defense system in carcinogenesis by decreasing TBARS contents, $H_2O_2$, organic peroxides. Therefore, vitamin E seemed to protect cell from free radical damage in carcinogenesis. By DHEA supplement liver weight and liver/body ratio were increased, the area and number of GST-P positive foci, the activities of catalase, GR, total GPx, GST and the TBARS contents were decreased significantly. On the other hand Cu/Zn-SOD and G6Pase activities weren't changed by DHEA supplement. In hepatocarcinogenesis the activities of antioxidant enzymes weren't increased by DHEA supplement. DHEA did not increase the oxidative stress, while DHEA seems to have anticarcinogenic effect in rats hepatocarcinogenesis.

• Journal of Life Science
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• v.9 no.6
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• pp.684-691
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• 1999

Gamdutang aqua-acupuncture solution (GAS), Gamdutang water-extracted solution (GWS) and Dae-Gamdutang aqua-acupuncture solution (DGAS) were prepared and tested for chemopreventive potentials. GAS was potent inducer of quinone reductase (QR) activity in Heapa1c1c7 murine hepatoma cells in culture, whereas GWS is less potent. GAS, GWS and DGAS were significantly induced QR activity in cultured rat normal liver cell, Ac2F. Glutathione (GSH) levels were increased about 1.8, 1.0 and 1.1 fold with GAS, GWS and DGAS in Hepa1c1c7 cells, respectively. In addition glutathione S-transferase (GST) activity was increased with GAS, GWS and DGAS. The effects of GAS, GWS and DGAS on the growth of Acanthamoeba castellanii were tested. Proliferation of A. castellanii was inhibited by GAS, GWS and DGAS at concentrations of 1 $\times$ and 5$\times$. These results suggest that GAS has chemopreventive potential by inducing QR and GST activities, increasing GSH levels and inhibition of polyamine metabolism.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6403-6407
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• 2012

Detoxifying enzymes are present in most epithelial cells of the human gastrointestinal tract where they protect against xenobiotics which may cause cancer. Induction of examples such as glutathione S-transferase (GST) and its thiol conjugate, glutathione (GSH) as well as NAD(P)H: quinoneoxidoreductase (NQO1) facilitate the excretion of carcinogens and thus preventing colon carcinogenesis. Pterostilbene, an analogue of resveratrol, has demonstrated numerous pharmacological activities linked with chemoprevention. This study was conducted to investigate the potential of pterostilbene as a chemopreventive agent using the HT-29 colon cancer cell line to study the modulation of GST and NQO1 activities as well as the GSH level. Initially, our group, established the optimum dose of 24 hours pterostilbene treatment using MTT assays. Then, effects of pterostilbene ($0-50{\mu}M$) on GST and NQO1 activity and GSH levels were determined using GST, NQO1 and Ellman assays, respectively. MTT assay of pterostilbene ($0-100{\mu}M$) showed no cytotoxicity toward the HT-29 cell line. Treatment increased GST activity in the cell line significantly (p<0.05) at 12.5 and $25.0{\mu}M$. In addition, treatment at $50{\mu}M$ increased the GSH level significantly (p<0.05). Pterostilbene also enhanced NQO1 activity significantly (p<0.05) at $12.5{\mu}M$ and $50{\mu}M$. Hence, pterostilbene is a potential chemopreventive agent capable of modulation of detoxifiying enzyme levels in HT-29 cells.

• Journal of Nutrition and Health
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• v.31 no.6
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• pp.1014-1023
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• 1998

The influences of fish oil and different levels of vitamin I supplement on hepatocellular chemical carcinogenesis have been studied. Male Sprague-Dawley rats received diethylnitrosamine (DEN)(200mg/kg body weight) and were subjected to two-thirds partial hepatectomy to induce murine chemical hepatocarcinogenic procedure. Placental glutathione S-transferase(GST-P) positive foci area, antioxidant enzymes(Cu/Zn-superoxide dismutase(SOD), catalase, glutathione reductase (GR), total- glutathione peroxidase (TGPx), glutathione S -transferase (GST)), glucose 6-phosphatase (G6Pase) activities, and lipid peroxidation of microsomes(thiobarbituric acid reactive substances (TBARS)) were measured. Experimental animals were fed 15% corn or fish oil with 0, 40, 1,000, 10,000IU vitamin E /kg diet for 8 weeks. Vitamin E supplements decreased the area of GST-P positive foci in both groups. The higher the vitamin E levels, the smaller the area of GST-P positive foci were noticed. Compared to 0 IU vitamin E, 40 IU in corn oil and 1,000 IU in fish oil groups were effective in decreasing G57-P positive foci area. Fish oil groups tended to have smaller area of GST-P positive foci. fish oil groups showed lower body weight, lower activities of Cu/Zn-SOD and TGPx, higher TBARS contents, higher activities of GST, catalase, G6Pase, GR and higher liver/body ratio than corn oil groups. As the level of vitamin I increased, GST-P positive foci count, catalase activities, and TBARS tended to decrease. G6Pase activities tended to increase in both groups. At higher vitamin E levels, GST activities tended to decrease in fish oil groups. These results suggest that vitamin I has suppressive offects on hepatocellular chemical carcinogenesis probably through antioxidant eH:cts decreasing TBARS contents, $H_2O$$_2$, and organic peroxides. fish oil tended to have greated suppressive offects than corn oil on hepatocellular carcinogenesis. (Korean J Nutrition 31(6) : 1014-1023, 1998)

• Biomedical Science Letters
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• v.6 no.1
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• pp.29-36
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• 2000

To investigate the effect of injection frequency of bromobenzene on the liver damage, bromobenzene (400 mg/kg, i.p.) was given daily to rats for six days. All experimental animals were sacrificed at 24 hours after the last injection. Morphological changes of the liver were observed under a light microscopic examination. Functional changes of the liver were evaluated by the measurement of alanine aminotransferase activity. To clarify the cause of discrepancy in liver damage, hepatic glutathione (GSH) content, glutathione S-transferase (GST) and aniline hydroxylase (AH) activities were determined. In the experiments of daily bromobenzene treatments, the sacrificed animals at six day (6 time-injected animals) showed slighter liver damage than those sacrificed at 3 day (3 time-injected ones), based on the liver morphological or functional findings; the decreasing ratio of GSH content and increasing ratio of liver GST and AH activities in the 6 time-injected group were higher than those in the 3 time-injected one.

• Biomedical Science Letters
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• v.6 no.2
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• pp.101-107
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• 2000

To evaluate the effect of intervals of bromobenzene treatment on the liver damage, the bromobenzene (400 mg/kg, i.p.) was given to rats at either one day or two days interval at three times. All the experimental animals were sacrificed at 24 hours after the last injection. Liver morphological changes were observed under a light microscopic examination and liver functional changes were determined by the measurement of alaine aminotransferase (ALT) activity and hepatic malondialdehyde (MDA) content. The experimental to examine the cause of liver damage were cytochrome P45O, glutathione (GSH) content and glutathione S-transferase (GST) activities. The results are summarized as follows; Based on the liver morphological and functional findings, the daily bromobenzene-treated rats (ED) showed the more severe liver damage than every other day bromobenzene-treated rats (EOD). The hepatic cytochrome P45O content was higher in EOD group than that in ED group. And the increasing rate of hepatic GST activity and decreasing rate of GSH content to the control were higher in EOD group than that in ED group. In conclusion, the treatment of bromobenzene intermittently to the rats may lead to more reduced liver injury compared with the continuously treated animals when both cases are treated with the same dose and frequency, and it may be caused by the enhancement of bromobenzene metabolism.