• Archives of Pharmacal Research
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• 제29권2호
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• pp.172-177
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• 2006

Hepatotoxic potential of 2, 3-dibromopropene (2, 3-DBPE) and its conjugation with glutathione (GSH) were investigated in male ICR mice. Treatment of mice with 20, 50, and 100 mg/kg of 2, 3-DBPE for 24 h caused elevation of serum alanine aminotransferase and aspartate aminotransferase activities. The hepatic content of GSH was not changed by 2, 3-DBPE. Meanwhile, the GSH content was slightly reduced when mice were treated with 2, 3-DBPE for 6 h and significantly increased 12 h after the treatment. Subsequently, a possible formation of GSH conjugate of 2, 3-DBPE was investigated in vivo. After the animals were treated orally with 20, 50, and 100 mg/kg of 2, 3-DBPE, the animals were subjected to necropsy 6, 12, and 24 h later. A conjugate of S-2-bromopropenyl GSH was identified in liver and serum treated with 100 mg/kg of 2, 3-DBPE by using liquid chromatography-electrospray ionization tandem mass spectrometry. The protonated molecular ions $[M+H]^+$ of S-2-bromopropenyl GSH were observed at m/z 425.9 and 428.1 in the positive ESI spectrum with a retention time of 6.35 and 6.39 min, respectively. In a time-course study in livers following an oral treatment of mice with 100 mg/kg of 2, 3-DBPE for 6, 12, and 24 h, the 2, 3-DBPE GSH conjugate was detected maximally 6 h after the treatment. The present results suggested that 2, 3-DBPE-induced hepatotoxicity might be related with the production of its GSH conjugate.

• Toxicological Research
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• 제26권2호
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• pp.101-108
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• 2010

Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses or extraction solvents in workplace. In the present study, immunotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose response or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 hr for time course. S-Butyl GSH was identified in spleen by liquid chromatography-electrospray ionization tandem mass spectrometry. Splenic GSH levels were significantly reduced by single treatment with 1-BB. S-Butyl GSH conjugates were detected in spleen from 6 hr after treatment. Oral 1-BB significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular interlukin-2 in response to Con A. Our present results suggest that 1-BB could cause immunotoxicity as well as reduction of splenic GSH content, due to the formation of GSH conjugates in mice. The present results would be useful to understand molecular toxic mechanism of low molecular weight haloalkanes and to develop biological markers for exposure to haloalkanes.

• Journal of Nutrition and Health
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• 제39권2호
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• pp.100-108
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• 2006

This study was conducted to investigate whether dietary factors, normal fat and genistein leads to beneficial improvement of lipid metabolism and oxidative stress in adult hyperlipidemic male rats. Seven wk-old male SD rats were fed high fat diet (15% fat, 1% cholesterol) for 4 wks for induction of hyperlipidemic model rat. Weight-matched rats were then assigned to four groups according to dietary fat level (7% or 15% fat) and genistein contents (0 or 320 mg/kg diet). Food intake was significantly decreased by both high fat intake and genistein supplementation compared with normal fat intake and genistein no supplementaion. But weight gain was significantly decreased by genistein supplementation in normal fat intake compared with the other groups. Total lipid, total cholesterol and triglyceride in serum and liver were significantly decreased by normal fat intake compared with high fat intake. But total cholesterol in liver was significantly increased by genistein supplementation in both high fat and normal fat intake. TBARS in serum and liver was less produced by normal fat intake compared with high fat intake but TBARS in liver was significantly increased by genistein supplementation compared with genistein no supplementation in normal fat intake. Glutathione reductase activity in erythrocytes was significantly reduced by genistein supplementation in normal fat intake compared with the other groups. Glutathione peroxidase and glutathione reductase activities in liver were significantly inhibited by normal fat intake compared with high fat intake. Catalase activity in liver was significantly increased by genistein supplementation compared with genistein no supplementation in high fat intake. Nitrite was significantly decreased by normal fat intake compared with high fat intake. These results suggest that normal fat intake has the treatment effect against risk factors related with cardiovascular disease by reducing lipid profiles, lipid peroxidation. And genistein shows action as a antioxidant replacing antioxidant enzymes but also may act as prooxidant causing the production of TBARS.

• Nutrition Research and Practice
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• 제2권2호
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• pp.80-84
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• 2008

Beneficial effects of dehydroepiandrosterone (DHEA) supplement on age-associated chronic diseases such as cancer, cardiovascular disease, insulin resistance and diabetes, have been reported. However, its mechanism of action in hepatocellular carcinoma in vivo has not been investigated in detail. We have previously shown that during hepatocellular carcinogenesis, DHEA treatment decreases formation of preneoplastic glutathione S-transferase placental form-positive foci in the liver and has antioxidant effects. Here we aimed to determine the mechanism of actions of DHEA, in comparison to vitamin E, in a chemically-induced hepatocellular carcinoma model in rats. Sprague-Dawley rats were administered with control diet without a carcinogen, diets with 1.5% vitamin E, 0.5% DHEA and both of the compounds with a carcinogen for 6 weeks. The doses were previously reported to have anti-cancer effects in animals without known toxicities. With DHEA treatment, cytosolic malate dehydrogenase activities were significantly increased by ${\sim}5$ fold and glucose 6-phosphate dehydrogenase activities were decreased by ${\sim}25%$ compared to carcinogen treated group. Activities of Se-glutathione peroxidase in the cytotol was decreased siguificantly with DHEA treatment, confirming its antioxidative effect. However, liver microsomal cytochrome P-450 content and NADPH-dependent cytochrome P-450 reductase activities were not altered with DHEA treatment. Vitamin E treatment decreased cytosolic Se-glutathione peroxidase activities in accordance with our previous reports. However, vitamin E did not alter glucose 6-phosphate dehydrogenase or malate dehydrogenase activities. Our results suggest that DHEA may have decreased tumor nodule formation and reduced lipid peroxidation as previously reported, possibly by increasing the production of NADPH, a reducing equivalent for NADPH-dependent antioxidant enzymes. DHEA treatment tended to reduce glucose 6-phosphate dehydrogenase activities, which may have resulted in limited supply for de novo synthesis of DNA via inhibiting the hexose monophophaste pathway. Although both DHEA and vitamin E effectively reduced preneoplastic foci in this model, they seemed to fimction in different mechanisms. In conclusion, DHEA may be used to reduce hepatocellular carcinoma growth by targeting NADPH synthesis, cell proliferation and anti-oxidant enzyme activities during tumor growth.

• Archives of Pharmacal Research
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• 제22권2호
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• pp.99-107
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• 1999

A series of organosulfur compounds were synthesized with the aim of developing chemopreventive compounds active against hepatotoxicity and chemical carcinogesis. 2-(Allylthio) prazine (2-AP) was effective in inhibiting cytochrome P450 2E1-mediated catalytic activities and protein expression, and in inducing microsomal epoxide hydrolase and major glutathione S-transferases. 2-AP reduced the hepatotoxicity caused by toxicant sand elevated cellular GSH content. Development of skin tumors, pulmonary adenoma and aberrant crypt foci in colon by various chemical carcinogens was inhibited by 2-AP pretreatment. Anticarcinogenic effects of 2-AP at the stage of initiation of tumors were also observed in the aflatoxin B1 ($AFB_1$)-induced three-step medium-term hepatocarcinogenesis model. Reduction of $AFB_1$-DNA adduct by 2-AP appeared to result from the decreased formation of $AFB_1$-8,9-epoxide via suppression of cytochrome P450, while induction of GST 2-AP increases the excretion of glutathione-conjugated $AFB_1$ . 2-AP was a radioprotective agent effective against the lethal dose of total body irradiation and reduced radiation-induced injury in association with the elevation of detoxifying gene expression. 2-AP produces reactive oxygen species in vivo, which is not mediated with the thiol-dependent production of oxidants and that NF-KB activation is not involved in the induction of the detoxifying enzymes. the mechanism of chemoprotection by 2-AP may involve inhibition of the P450-mediated metabolic activation of chemical carcinogens and enhancement of electrophilic detoxification through induction of phase II detoxification enzymes which would facilitate the clearance of activated metabolites through conjugation reaction.

• BMB Reports
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• 제52권4호
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• pp.271-276
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• 2019

Zingerone (ZGR), a phenolic alkanone isolated from ginger, has been reported to possess pharmacological activities such as anti-inflammatory and anti-apoptotic effects. This study was initiated to determine whether ZGR could modulate renal functional damage in a mouse model of sepsis and to elucidate the underlying mechanisms. The potential of ZGR treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured by assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with ZGR resulted in elevated plasma levels of BUN and creatinine, and of protein in urine in mice with CLP-induced renal damage. Moreover, ZGR inhibited nuclear $factor-{\kappa}B$ activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. ZGR treatment also reduced the plasma levels of interleukin-6 and tumor necrosis $factor-{\alpha}$, reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. Our study showed renal suppressive effects of zingerone in a mouse model of sepsis, suggesting that ZGR protects mice against sepsis-triggered renal injury.

• 한국초지조사료학회지
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• 제43권2호
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• pp.109-115
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• 2023

Ammonium (NH₄⁺) serves as a nitrogen source, but its elevated levels can hinder plant growth and production. Excess NH₄⁺ with α-ketoglutarate is assimilated into glutamate, a precursor of proline and glutathione (GSH). This study aimed to investigate the effects of excessive NH₄⁺ on the regulation of proline and GSH synthesis. Detached leaves from oilseed rape (Brassica napus L.) were fed with 0, 50, 100, 500, and 1000 mM NH₄Cl for 16 h. As the NH₄⁺ concentrations increased, the leaves exhibited progressive wilting and yellowing. Furthermore, total carotenoid and chlorophyll concentrations declined in response to all NH₄⁺ treatments, with the lowest levels observed in 1000 mM NH₄⁺ treatment. Hydrogen peroxide (H₂O₂) concentration showed a minor increase at low NH₄⁺ concentration (50 and 100 mM) treatments but a significant increase at high NH₄⁺ (500 and 1000 mM), which was consistent with the localization of H₂O₂. Amino acid concentrations increased with increasing in NH₄⁺ concentration, while the protein concentration displayed the opposite trend. Proline and cysteine concentrations exhibited a gradual increase in response to increasing NH₄⁺ concentrations. However, GSH concentrations rose only in the 50 mM NH₄⁺ treatment and decreased in the 500 and 1000 mM NH₄⁺ treatments. These results indicate that excessive NH₄⁺ is primarily assimilated into proline, while GSH synthesis is adversely affected.

• Asian-Australasian Journal of Animal Sciences
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• 제16권2호
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• pp.217-221
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• 2003

The present investigation was undertaken to study status of erythrocytic antioxidant enzymes in normal cycling and $\alpha$- tocopherol supplemented anestrus buffalo heifers. The pre-supplementation erythrocytic activities of superoxide dismutase (U/mg Hb), glutathione peroxidase (U/mg Hb) and glucose-6-phosphate dehydrogenase (U/g Hb) upregulated significantly (p<0.05) in anestrus heifers ($10.08{\pm}0.09$, $14.09{\pm}0.54$, $9.25{\pm}0.29$) when compared to normal cycling ones ($6.93{\pm}0.04$, $11.61{\pm}0.19$, $5.58{\pm}0.26$). The oral supplementation of $\alpha$-tocopherol (a) 3,000 mg per week per animal in anestrus heifers declined erythrocytic superoxide dismutase and glucose-6-phosphate dehydrogenase activities significantly (p<0.01) but led to non-significant increase in erythrocytic glutathione peroxidase activity. Results indicated that supplementation of $\alpha$-tocopherol to anestrus buffalo heifers mitigated the effects of oxidative stress to improve their antioxidant status.

• Journal of Microbiology and Biotechnology
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• 제16권7호
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• pp.1041-1046
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• 2006

Selenium-containing peptide (selenium peptide) was produced by autolysis of total proteins of Saccharomyces cerevisiae grown with inorganic selenium. Selenium peptide exhibited antioxidant activity as a glutathione peroxidase (GPx) mimic, and its activity was dependent on the hydrolysis methods. The GPx-like activity of the hydrolyzed selenium peptide increased 2.7-folds when digested by protease, but decreased by acid hydrolysis. During the autolysis of the yeast cell, the GPx-like activity and selenium content increased 4.3- and 2.3-folds, respectively, whereas the average molecular weight (MW) of selenium peptide decreased 70%. The GPx-like activity was dependent on the MW of selenium peptide and was the highest (220 U/mg protein) at 9,500 dalton. The maximum GPx-like activity (28,600 U/g cell) was obtained by 48 h of autolysis of the cells, which were precultured with 20 ppm of selenate. Selenium peptide showed little toxicity, compared with highly toxic inorganic selenium. These results show the potential of selenium peptide as a nontoxic antioxidant that can be produced by simple autolysis of yeast cells.

• Asian-Australasian Journal of Animal Sciences
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• 제20권9호
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• pp.1433-1437
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• 2007

Two field trials were carried out to evaluate the performance of a soluble glass copper, cobalt and selenium bolus for maintaining adequate levels of the three trace elements in yaks. Forty yaks were used in trial 1 and 60 yaks were used in trial 2. In each trial two commercial soluble glass boluses were administered to half of the yaks. Blood samples were taken from the jugular vein at day 0, 30, 60, 90 in trial 1 and at day 0, 45, 75 and 105 in trial 2. The samples were analysed for copper status (serum caeruloplasmin activity and copper concentration), cobalt status (serum vitamin $B_{12}$ concentration and cobalt concentration), selenium status (erythrocyte glutathione peroxidase activity and selenium concentration) and serum zinc concentration. The erythrocyte glutathione peroxidase activities, serum caeruloplasmin activities and serum vitamin $B_{12}$ concentrations for trial 1 and 2 were all significantly increased for the bolused yaks (p<0.001 or p<0.01) on all sampling days. The bolused yaks had a significantly higher selenium and copper status in serum than the control yaks on all sampling days in trial 1 and 2 (p<0.05 or p<0.01). There were no significant differences in zinc and cobalt concentrations between the bolused yaks and the controls.