• Tuberculosis and Respiratory Diseases
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• v.41 no.3
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• pp.222-230
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• 1994

Background: Paraquat, a widely used herbicide, is extremely toxic, causing multiple organ failure in humans. Paraquat especially leads to irreversible progressive pulmonary fibrosis, which is related to oxygen free radicals. However, its biochemical mechanism is not clear. Natural mechanisms that prevent damage from oxygen free radicals include changes in glutathione level, G6PDH, superoxide dismutase(SOD), catalase, and glutathione peroxidase. The authors think catalase is closely related to paraquat toxicity in the lungs Method: The effects of 3-amino-1,2,4-triazole(aminotriazole), a catalase inhibitor, on mice administered with paraquat were investigated. We studied the effects of aminotriazole on the survival of mice administered with paraquat, by comparing life spans between the group to which paraquat had been administered and the group to which a combination of paraquat and aminotriazole had been administered. We measured glutathion level, glucose 6-phosphate dehydrogenase(G6PDH), superoxide dismutase(SOD), catalase, and glutathione peroxidase(GPx) in the lung tissue of 4 groups of mice: the control group, group A(aminotriazole injected), group B(paraquat administered), group C(paraquat and aminotriazole administered). Results: The mortality of mice administered with paraquat which were treated with aminotriazole was significantly increased compared with those of mice not treated with aminotriazole. Glutathione level in group B was decreased by 20%, a significant decrease compared with the control group. However, this level was not changed by the administration of aminotriazole(group C). The activity of G6PDH in all groups was not significantly changed compared with the control group. The activities of SOD, catalase, and glutathione peroxidase(GPx) in the lung tissue were significantly decreased by paraquat administration(group B); catalase showed the largest decrease. Catalase and GPX were significantly decreased by aminotriazole treatment in mice administered with paraquat but change in SOD activity was not significant(group C). Conclusion: Decrease in catalase activity by paraquat suggests that paraquat toxicity in the lungs is closely related to catalase activity. Paraquat toxicity in mice is enhanced by aminotriazole administration, and its result is related to the decrease of catalase activity rather than glutathione level in the lungs. Production of hydroxyl radicals, the most reactive oxygen metabolite, is accelerated due to increased hydrogen peroxide by catalase inhibition and the lung damage probably results from nonspecific tissue injury of hydroxyl radicals.

• Applied Biological Chemistry
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• v.48 no.1
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• pp.53-59
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• 2005

The effect of various stressors such as reductant ascorbic acid, signalling molecules (salicylic acid and methyl jasmonic acid), heavy metals $(NiCl_2,\;and\;MnSO_4)$ and NaCl on the glutathione peroxidase (GPX) activities and isoenzyme expression patterns were investigated in rice seedling roots. Total GPX activity increased according to the increase of ascorbic acid concentration. Prominent enhancement of GPX1 isozyme due to ascorbic acid contributed to the increase of total GPX activity. GPX showed different reactivity toward salicylic acid and methyl jasmonic acid. GPX activity increased at 0.1 mM salicylic acid, and then decreased thereafter. However, GPX increased gradually in a methyl jasmonic acid concentration-dependent manner, and 3 fold increase of GPX activity was found at 1 mM methyl jasmonic acid. Moreover, GPX1 isozyme increased according to the increase of salicylic acid, while GPX1 isozyme decreased according to the increase of methyl jasmonic acid. When metal ions were treated, GPX activity increased considerably according to the increase of $NiCl_2$ concentration, however, GPX activity increased about 2 fold at 0.5 mM $CuSO_4$ and then decreased. Enhancement of GPX1 isozyme contributed to the increase of total GPX activities in $NiCl_2-treated$ and $MnSO_4-treated$ rice seedlings. Total GPX activity increased 1.7 fold in response to 300 mM NaCl. Especially GPX2 isozyme showed gradual increase according to the increase of NaCl concentration.

• Molecules and Cells
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• v.39 no.8
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• pp.631-638
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• 2016

Glutathione peroxidase 3 (GPx3), an antioxidant enzyme, acts as a modulator of redox signaling, has immunomodulatory function, and catalyzes the detoxification of reactive oxygen species (ROS). GPx3 has been identified as a tumor suppressor in many cancers. Although hyper-methylation of the GPx3 promoter has been shown to down-regulate its expression, other mechanisms by which GPx3 expression is regulated have not been reported. The aim of this study was to further elucidate the mechanisms of GPx3 regulation. GPx3 gene analysis predicted the presence of ten glucocorticoid response elements (GREs) on the GPx3 gene. This result prompted us to investigate whether GPx3 expression is regulated by the glucocorticoid receptor (GR), which is implicated in tumor response to chemotherapy. The corticosteroid dexamethasone (Dex) was used to examine the possible relationship between GR and GPx3 expression. Dex significantly induced GPx3 expression in H1299, H1650, and H1975 cell lines, which exhibit low levels of GPx3 expression under normal conditions. The results of EMSA and ChIP-PCR suggest that GR binds directly to GRE 6 and 7, both of which are located near the GPx3 promoter. Assessment of GPx3 transcription efficiency using a luciferase reporter system showed that blocking formation of the GR-GRE complexes reduced luciferase activity by 7-8-fold. Suppression of GR expression by siRNA transfection also induced down-regulation of GPx3. These data indicate that GPx3 expression can be regulated independently via epigenetic or GR-mediated mechanisms in lung cancer cells, and suggest that GPx3 could potentiate glucocorticoid (GC)-mediated anti-infla-mmatory signaling in lung cancer cells.

• Nutrition Research and Practice
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• v.4 no.2
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• pp.114-120
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• 2010

The effects of grape seeds extract and grape peels extract prepared from grape pomace on the activity of antioxidant enzymes, degree of lipid peroxidation in serum and liver tissue were investigated in rabbits fed on high cholesterol diet. New Zealand white rabbits were divided as follows ; 1) NOR (normal group); 2) CHOL (cholesterol group); 3) GSH (cholesterol + grape seed extract group); 4) GPE (cholesterol + grape peel extract); 5) GSP (cholesterol + grape seed powder); 6) GPP (cholesterol + grape peel powder); 7) GE (cholesterol + grape seed and peel extract); 8) GP (cholesterol + grape seed and peel powder). Eight groups of rabbits were studied for 8 weeks. At the end of the experimental period, rabbits were sacrificed and the liver tissue were removed. Then, GSH, GPx, GST, CAT and MDA in the liver were measured. In liver tissues, total glutathione contents (GSH), glutathione peroxidase (GPx) and catalase (CAT) activity, which was significantly higher by grape seed extract supplementation. The level of malondialdehyde (MDA) was lower in the serum of rabbits fed grape seed extract or grape peel powder plus cholesterol than in the serum of rabbits fed cholesterol alone. It is therefore likely that grape seed extract prepared from grape pomace functioned as antioxidants in vivo, negating the effects of the oxidative stress induced by 1% cholesterol diet. The grape seed extract was found effective in converting the oxidized glutathione into reduced glutathione, and in removing $H_2O_2$ that is created by oxidative stress. The grape peel powder was found to have small influence on reduced glutathione content, CAT and GPX activity, but it increased GST activity in liver tissues, resulting in promoting the combination of lipid peroxide and glutathione (GSH), and further, lowering the formation of lipid peroxide in the serum. Therefore, grape pomace (grape seed extract and grape peel powder) supplementation is considered to activate the antioxidant enzyme system and prevent damage with hypercholesterolemia.

• Nutritional Sciences
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• v.3 no.1
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• pp.11-17
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• 2000

This study was intended to examine whether dehydroepiandrosterone (DHEA) and dietary fat level or source could modulate glutathione utilizing detoxifying system activity and the cytosolic NADPH generation in rat liver. Male Sprague-Dawley rats were fed semipurifed diet containing either 2%(w/w) corn oil (low level of corn oil diet: 5 ca% of fat) 15% corn oil (high level of corn oil diet: 31 cal% of fat) or 13% sardine oil plus 2% corn oil(high level of fish oil diet: 31 cal% of fat) for 9 weeks. Half of the rats in each diet group were fed a diet supplemented with 0.2% DHEA (w/w). DHEA administration increased plasma total cholesterol level in low corn oil diet-fed rats. The high fish oil diet significantly decreased plasma total cholesterol level compared to the high corn oil diet. Plasma triglyceride level was not significantly changed by DHEA administration and dietary fat level and source. Fasting plasma glucose level was increased by DHEA administration and fish oil diet. Glucose 6-phosphate dehydrogenase activity in liver tissue was significantly increased by DHEA administration and high fat diet, especially fish oil diet. Malic enzyme activity in liver tissue was significantly increased by DHEA administration and high fat diet, especially fish oil diet. Malic enzyme activity in liver tissue was significantly increased by DHEA administration. DHEA suppressed the glutathione peroxidase, glutathione-dependent enzymes compared to the low corn oil diet, while fish oil diet elevated the activity of glutathione peroxidase and glutathione reductase compared to corn oil diet. These results suggest that DHEA administration and high level of corn oil diet may suppress the cellular detoxifying system activity through reduction of glutathione utilization, while the fish oil diet did not show these effects.

• BMB Reports
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• v.34 no.3
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• pp.278-283
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• 2001

Antioxidant and redox enzyme activities are known to be involved in the cellular responses to various stresses. Their variations were observed according to the growth cycle of the fission yeast Schizosaccharomyces pombe. Peroxidase activity appeared to be notably higher in the early exponential phase than in the mid-exponential and stationary phases. However, catalase activity showed a variation pattern resembling the growth curve. Glutathione S-transferase activity was higher in the early exponential and late stationary phases. Activities of the two redox enzymes, thioredoxin and thioltransferase (glutaredoxin), were high in the stationary phase. However, their activities appeared to increase from the early exponential to mid-exponential phase. Total glutathione content had a varying pattern similar to that of thioredoxin and thioltransferase. However, its content in the early exponential phase was high. These results propose that antioxidant and redox enzymes tested are also involved in the mechanism of cell growth.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5421-5425
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• 2013

Background: To assess the antioxidant effects of gamma-oryzanol on human prostate cancer cells. Materials and Methods: Cytotoxic activity of gamma-oryzanol on human DU145 and PC3 prostate cancer cells was determined by proliferation assay using 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) reagent. mRNA levels of genes involved in the intracellular antioxidant system, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GSR) were determined by reverse transcription-polymerase chain reaction (RT-PCR). Cancer cell lysates were used to measure lipid peroxidation using thiobarbituric acid reactive substance (TBARS). Glutathione contents of the cell lysates were estimated by the reaction between sulfhydryl group of 5, 5'-dithio (bis) nitrobenzoic acid (DTNB) to produce a yellow-color of 5-thio-2-nitrobenzoic acid using colorimetric assay. Catalase activity was also analysed by examining peroxidative function. Protein concentration was estimated by Bradford's assay. Results: All concentrations of gamma-oryzanol, 0.1-2.0mg/ml, significantly inhibited cell growth in a dose- and time-dependent fashion in both prostate cancer cell lines, DU145 and PC3. Gene expression of catalase in DU145 and PC3 exposed to gamma-orizanol at 0.5mg/ml for 14 days was down regulated, while mRNA of GPX was also down regulated in PC3. The MDA and glutathione levels including catalase activity in the cell lysates of DU145 and PC3 treated with gamma-oryzanol 0.1 and 0.5mg/ml were generally decreased. Conclusions: This study highlighted effects of gamma-oryzanol via the down-regulation of antioxidant genes, catalase and GPX, not cytotoxic roles. This might be interesting for adjuvant chemotherapy to make prostate cancer cells more sensitive to free radicals. It might be useful for the reduction of cytotoxic agents and cancer chemoprevention.

• Biomedical Science Letters
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• v.12 no.1
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• pp.49-52
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• 2006

To elucidate the effect of antioxidant complex containing $\beta-carotene$, vitamin E, vitamin C, Ginkgo Biloba leaf extract and selenium on oxygen :tree radical production and detoxification system, rats were fed normal diet and normal diet with antioxidant complex 0.1%, 0.3% and 0.5% for 3 weeks. Feed efficiency ratio, changes in body weight, weight gain and amounts of feces of rat are similar in four groups. Liver weight per body weight and hepatic lipid peroxide weight increased in 0.5% group. However, hepatic glutathione contents in all antioxidant complex added groups were significantly increased compare with normal control group. On the other hand, the activity of xanthine oxidase was a little increased due to the amounts of antioxidant complex. Superoxide dismutase and gutathione peroxidase activity of 0.1% antioxidant complex added group were increased about $10{\sim}20%$ in comparison to normal control group. These results suggest that the supplementation of antioxidant complex 0.1% to basal diet may reduce the hepatic damage caused by free radicals.

• Journal of Oriental Neuropsychiatry
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• v.19 no.3
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• pp.129-142
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• 2008

Objective: The purpose of this study was to evaluate the antioxidative effects of the extract of Scolopendra subspinipes which has been used mainly for detoxication in the oriental medicine and reported to have sedative action, antiinflammatory effect, antihypertensive property and immunity enhancing activity. Method: Inhibitory activities on oxygen radical generating enzymes (aldehyde oxidase and xanthine oxidase) and increasing activities on oxygen radical scavenging enzymes (superoxide dismutase, glutathione peroxidase, glutathione-S-transferase) were investigated. Furthermore, the content of glutathione in the mouse brain, DPPH radical scavenging activity and also anti-lipid peroxidative effects in vivo and in vitro were estimated. Results: The extract showed weak inhibitory effects on the activities of aldehyde oxidase and xanthine oxidase which are oxygen radical generating enzymes. The extract inhibited lipid peroxidation with 26.1% against control group at 500 mg/kg in vivo and with 11.2% against control group at 10 mg/kg in vitro in a dose-dependent manner, which means this drug may protect radical-induced cell damages. The extract showed dose-dependently the scavenging effect on DPPH radical with 24.8% activity at 10 mg/ml in vitro. The extract enhanced the activities of superoxide dismutase, glutathione peroxidase and glutathione-S-transferase, which are oxygen radical scavenging enzymes, with 28.9%, 22.3% and 23.1%, respectively at 500mg/kg in vivo. Finally, this extract strongly increased the glutathione content in the mouse barin. Conclusion: Above results indicated that Scolopendra subspinipes can be useful for the protection or treatment of some diseases caused by reactive oxygen species.

• International Journal of Vascular Biomedical Engineering
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• v.2 no.2
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• pp.1-9
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• 2004

The history of studies in biology regarding reactive oxygen species (ROS) is approximately 40 years. During the initial 30 years, it appeared that these studies were mainly focused on the toxicity of ROS. However, recent studies have identified another action regarding oxidative signaling, other than toxicity of ROS. Basically, it is suggested that ROS are reactive, and degenerate to biomolecules such as DNA and proteins, leading to deterioration of cellular functions as an oxidative stress. On the other hand, recent studies have shown that ROS act as oxidative signaling in cells, resulting in various gene expressions. Recently ROS emerged as critical signaling molecules in cardiovascular research. Several studies over the past decade have shown that physiological effects of vasoactive factors are mediated by these reactive species and, conversely, that altered redox mechanisms are implicated in the occurrence of metabolic and cardiovascular diseases ROS is a collective term often used by scientist to include not only the oxygen radicals($O2^{-{\cdot}},\;{^{\cdot}}OH$), but also some non-radical derivatives of oxygen. These include hydrogen peroxide, hypochlorous acid (HOCl) and ozone (O3). The superoxide anion ($O2^{-{\cdot}}$) is formed by the univalent reduction of triplet-state molecular oxygen ($^3O_2$). Superoxide dismutase (SOD)s convert superoxide enzymically into hydrogen peroxide. In biological tissues superoxide can also be converted nonenzymically into the nonradical species hydrogen peroxide and singlet oxygen ($^1O_2$). In the presence of reduced transition metals (e.g., ferrous or cuprous ions), hydrogen peroxide can be converted into the highly reactive hydroxyl radical (${^{\cdot}}OH$). Alternatively, hydrogen peroxide may be converted into water by the enzymes catalase or glutathione peroxidase. In the glutathione peroxidase reaction glutathione is oxidized to glutathione disulfide, which can be converted back to glutathione by glutathione reductase in an NADPH-consuming process.