OBJECTIVES: This study aimed to estimate the effects of 4-nonylphenol (NP), a ubiquitously present surfactant in aquatic environments, on the anti-oxidant systems of the liver in the Far Eastern catfish Silurus asotus. METHODS: Changes in biochemical parameters involved in glutathione (GSH)-related and other anti-oxidant systems were analyzed following 4 weeks of 4-NP administration (0.1 and 1.0 mg/kg diet) via a formulated diet to catfish. RESULTS: 4-NP exposure induced an elevation in hepatic lipid peroxide levels and an accompanying decrease in reduced state GSH after 2 weeks, suggesting pro-oxidant effects of the chemical in catfish. This oxidative stress was associated with an inhibition of the GSH-utilizing enzyme glutathione peroxidase at the same time point. This inhibition was restored after 4 weeks. The activities of other anti-oxidant enzymes, i.e., glutathione reductase, superoxide dismutase and catalase were increased after 4 weeks. These enzyme increases occurred more strongly at the higher 4-NP concentration (1.0 mg/kg diet). CONCLUSIONS: 4-NP given to catfish at 0.1 to 1.0 mg/kg diet, concentrations relevant to environmental levels, depletes the endogenous anti-oxidant molecule GSH and temporarily inhibits GSH-related anti-oxidant enzymes. Such declines in anti-oxidant capacity and elevated oxidative stress seem to be compensated eventually by subsequent activation of various anti-oxidant enzyme systems.
Catalase ; Catfishes* ; Detergents* ; Diet ; Glutathione ; Glutathione Peroxidase ; Glutathione Reductase ; Liver ; Oxidative Stress ; Superoxide Dismutase

OBJECTIVES: This study aimed to estimate the effects of 4-nonylphenol (NP), a ubiquitously present surfactant in aquatic environments, on the anti-oxidant systems of the liver in the Far Eastern catfish Silurus asotus. METHODS: Changes in biochemical parameters involved in glutathione (GSH)-related and other anti-oxidant systems were analyzed following 4 weeks of 4-NP administration (0.1 and 1.0 mg/kg diet) via a formulated diet to catfish. RESULTS: 4-NP exposure induced an elevation in hepatic lipid peroxide levels and an accompanying decrease in reduced state GSH after 2 weeks, suggesting pro-oxidant effects of the chemical in catfish. This oxidative stress was associated with an inhibition of the GSH-utilizing enzyme glutathione peroxidase at the same time point. This inhibition was restored after 4 weeks. The activities of other anti-oxidant enzymes, i.e., glutathione reductase, superoxide dismutase and catalase were increased after 4 weeks. These enzyme increases occurred more strongly at the higher 4-NP concentration (1.0 mg/kg diet). CONCLUSIONS: 4-NP given to catfish at 0.1 to 1.0 mg/kg diet, concentrations relevant to environmental levels, depletes the endogenous anti-oxidant molecule GSH and temporarily inhibits GSH-related anti-oxidant enzymes. Such declines in anti-oxidant capacity and elevated oxidative stress seem to be compensated eventually by subsequent activation of various anti-oxidant enzyme systems.
Catalase ; Catfishes* ; Detergents* ; Diet ; Glutathione ; Glutathione Peroxidase ; Glutathione Reductase ; Liver ; Oxidative Stress ; Superoxide Dismutase

No abstract available.
Catalase ; Erythrocytes* ; Glutathione Peroxidase ; Humans ; Infant, Newborn* ; Superoxide Dismutase

This study was conducted to investigate the metallothionein induction by sodium selenite in mercuric Chloride intoxication. Mercuric chloride of 3.0 mg/kg of body weight was administered simultaneously with sodium selenite of either a high dosage of 2.5 mg/kg or low dosage of 1mg/kg via intraperitioneal injecion to rats. After the treatment, 6, 12, 24 and 72 hours later, mercury and selenium content in liver and kidney tissues, serum transaminase activities(SGOT, SGPT), metallothionein, glutathione, glutathione peroxidase sotivity and histological changes were determined. The results were summarized as follows on: 1. The combined administration of mercury and selenium significantly more decreased mercury concentrations in liver and kidney compared to the administration of mercury only. 2. The combined administration of mercury and selenium significantly more increased renal metallothionein compared to administration of mercury only. This phenomenon was more remarkable when a large dose(2.5 mg/kg) of selenium was administered with mercuric chloride. 3. Glutathione concentration, glutathione peroxidase activity in liver and kidney and serum transaininase activity(SGOT, SGPT) were less suppressed in the combined administration group than the mercury only group. 4. Histological damage in renal tissue was not revealed in rats treated with mercury and selenium. From the above results, selenium administered simultaneously with mercury decreased mercury concentration in liver and kidney, increased renal metallothionein concentration and decreased the toxicity of mercury. The hypothetic mechanism suggested is that selenium induces the metallothionein combined with Hg and redistributes Hg in tissues.
Animals ; Body Weight ; Glutathione ; Glutathione Peroxidase ; Kidney ; Liver ; Mercuric Chloride* ; Metallothionein ; Rats* ; Selenium ; Sodium Selenite* ; Sodium*

PURPOSE: To evaluate antioxidative and preventive effects of sea tangle extract on selenite-induced cataract formation. METHODS: Eighty SD rat pups were randomized into 8 groups. Group 1 received no injection of reagent (normal); Group 2 to 8 received injection of selenite (15 micromol/Kg, s.c.) was injected. In group 2 (control) and group 3, normal saline (i.p.) and ascorbic acid (i.p.) was injected on days 3~31. In groups 4~8, sea tangle extract (i.p.) was injected at a concentration of 12.5, 25, 50, 100, 200 mg/kg, respectively. Development of cataract was assessed and photographed weekly under slit lamp. Rat lenses were analyzed for antioxidant enzymes, glutathione peroxidase (GPx), superoxide dismutase and malondialdehyde. Furthermore, an amino acid analysis of sea tangle extract was performed. RESULTS: Significant differences (p<0.05) were seen in cataract development in group 7. Dense nuclear cataracts developed in 8 of 10 of the control group (group 2); Group 4~8 developed nuclear cataract with proportion of 6/10, 3/10, 2/10, 1/10, and 6/10 rats. In sea tangle injected group, levels of GPx were higher than in the ascorbic acid and control groups. In particular, group 7, injected with 100 mg/kg of sea tangle extract, showed significantly high level of enzyme. Results of the amino acid analysis showed sea tangle includes glutamate-glycine-cysteine, major constituents of glutathione (GSH). CONCLUSIONS: The glutamate-glycine-cysteine in sea tangle is supposed to increase the level of lens GSH and this may contribute to lowering cataract development. This study strongly supports the activity of sea tangle as an endogenous antioxidant and anticataract agent.
Animals ; Antioxidants ; Ascorbic Acid ; Cataract ; Glutathione ; Glutathione Peroxidase ; Malondialdehyde ; Rats ; Sodium Selenite ; Superoxide Dismutase

We investigated the selenium (Se) nutrition status in Korean infants. The mean serum Se concentration in infants was 66.9 microg/L, and it increased with increasing in infant age: 57.6 microg/L at 0-5 months, 71.8 microg/L at 6-11 months, and 75.5 microg/L at 12-24 months. Serum glutathione peroxidase (GPx) activity also increased with infant age. Serum Se concentration in infants was positively correlated with serum GPx activity (r = 0.565, p < 0.01). At 0-5 months, human milk-fed infants tended to have higher Se concentrations and GPx activity than those of formula-fed infants, but the result was not significant. With the introduction of supplemental feeding at 6-24 months of age, serum Se concentration was not different between the groups. Therefore, human milk feeding seemed to be more appropriate for infant Se nutrition than infant formula feeding during the first 6 months of life, but supplemental feeding became more important later to maintain good Se nutrition status.
Glutathione ; Glutathione Peroxidase ; Humans ; Infant ; Infant Formula ; Milk, Human ; Nutritional Status ; Selenium

OBJECTIVE: To investigate whether the acetaldehyde dehydrogenase 2 specific activator, Alda-1, can alleviate brain injury after cardiopulmonary resuscitation (CPR) by inhibiting cell ferroptosis mediated by acyl-CoA synthetase long-chain family member 4/glutathione peroxidase 4 (ACSL4/GPx4) pathway in swine. METHODS: Twenty-two conventional healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 8), and Alda-1 intervention group (CPR+Alda-1 group, n = 8) using a random number table. The swine model of CPR was reproduced by 8 minutes of cardiac arrest induced by ventricular fibrillation through electrical stimulation in the right ventricle followed by 8 minutes of CPR. The Sham group only experienced general preparation. A dose of 0.88 mg/kg of Alda-1 was intravenously injected at 5 minutes after resuscitation in the CPR+Alda-1 group. The same volume of saline was infused in the Sham and CPR model groups. Blood samples were collected from the femoral vein before modeling and 1, 2, 4, 24 hours after resuscitation, and the serum levels of neuron specific enolase (NSE) and S100 β protein were determined by enzyme-linked immunosorbent assay (ELISA). At 24 hours after resuscitation, the status of neurologic function was evaluated by neurological deficit score (NDS). Thereafter, the animals were sacrificed, and brain cortex was harvested to measure iron deposition by Prussian blue staining, malondialdehyde (MDA) and glutathione (GSH) contents by colorimetry, and ACSL4 and GPx4 protein expressions by Western blotting. RESULTS: Compared with the Sham group, the serum levels of NSE and S100β after resuscitation were gradually increased over time, and the NDS score was significantly increased, brain cortical iron deposition and MDA content were significantly increased, GSH content and GPx4 protein expression in brain cortical were significantly decreased, and ACSL4 protein expression was significantly increased at 24 hours after resuscitation in the CPR model and CPR+Alda-1 groups, which indicated that cell ferroptosis occurred in the brain cortex, and the ACSL4/GPx4 pathway participated in this process of cell ferroptosis. Compared with the CPR model group, the serum levels of NSE and S100 β starting 2 hours after resuscitation were significantly decreased in the CPR+Alda-1 group [NSE (μg/L): 24.1±2.4 vs. 28.2±2.1, S100 β (ng/L): 2 279±169 vs. 2 620±241, both P < 0.05]; at 24 hours after resuscitation, the NDS score and brain cortical iron deposition and MDA content were significantly decreased [NDS score: 120±44 vs. 207±68, iron deposition: (2.61±0.36)% vs. (6.31±1.66)%, MDA (μmol/g): 2.93±0.30 vs. 3.68±0.29, all P < 0.05], brain cortical GSH content and GPx4 expression in brain cortical was significantly increased [GSH (mg/g): 4.59±0.63 vs. 3.51±0.56, GPx4 protein (GPx4/GAPDH): 0.54±0.14 vs. 0.21±0.08, both P < 0.05], and ACSL4 protein expression was significantly decreased (ACSL4/GAPDH: 0.46±0.08 vs. 0.85±0.13, P < 0.05), which indicated that Alda-1 might alleviate brain cortical cell ferroptosis through regulating ACSL4/GPx4 pathway. CONCLUSIONS Alda-1 can reduce brain injury after CPR in swine, which may be related to the inhibition of ACSL4/GPx4 pathway mediated ferroptosis.
Male ; Animals ; Swine ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Ferroptosis ; Brain Injuries ; Glutathione ; Cardiopulmonary Resuscitation ; Ligases ; Iron

The effect of selenium on the tissue sulfhydryl group content and lipid peroxide-destorying enzyme system in the liver, kidney and testis of rat treated with mercury was investigated. The male rats were injected s.c. with HgCl2 (10 micromoles/kg BW) and orally received Na2SeO3 (13 micromoles/kg BW) simultaneously. After 3 days, liver, kidney and testis were removed and analyzed. Mercury decreased the total sulfhydryl group content in the kidney by 25% and the total glutathione content in the kidney and testis by 50% and 36%, respectively, with no changes in other tissues. There was 12% increase in the total sulfhydryl group but not in the total glutathione content in kidney by a simul-taneous treatment of Se and Hg. Glutathione peroxidase (GSH-Px) activities were decreased by 63% in the liver and 69% in the kidney, and glutathione reductase (GSH-Rd) activity was increased in the tests by 16% by the Hg treatment with no changes in Other tissues. Hg had no effect upon glutathione-S-transferase activities in all organs examined. Simultaneous Se treatment increased GSH-Rd activity in the kidney by 23% and GSH-Px activities in liver and kidney by 24% and 21%, respectively, compared to the Hg-treated group. These data indicate that the alleviation of Hg toxicity by Se treatment is well correlated with the protein sulfhydryl group content and GSH-Px activity.
Animal ; Glutathione/metabolism* ; Glutathione Peroxidase/analysis ; Glutathione Reductase/analysis ; Male ; Mercury/toxicity* ; Rats ; Selenium/pharmacology* ; Sulfhydryl Compounds/analysis*

PURPOSE: Resistance to anticancer chemotherapeutic drug remains a major obstacle in cancer chemotherapy. Multidrug-resistance(MDR) gene overexpression and detoxification by glutathione are believed to be involved in adriamycin and cisplatin resistance. We investigated change of p-glycoprotein(MDR gene product) expression, cellular glutathione content and glutathione peroxidase and glutathione transferase activities by hyperthermia to elucidate the synergistic mechanism of hyperthermia with chemotherapeutic agent. MATERIALS AND METHODS: Human renal cell carcinoma cell lines, Caki-1 and A-498 were used. Control temperature was 37OC and hyperthermia of 43OC was applied in 2 and 4 hours durations. P-glycoprotein expression was measured by flowcytometric examination using monoclonal antibody to p-glycoprotein. Glutathione content and activities of glutathione peroxidase and transferase were measured by biochemical methods. RESULTS: Glutathione content and activities of glutathione peroxidase and transferase were not changed by hyperthermia. However, p-glycoprotein expression was reduced by hyperthermia of 43OC. CONCLUSIONS: These results suggest that reduced p-glycoprotein expression by hyperthermia causes increased intracellular accumulation of chemotherapeutic agent by decreasing drug efflux mechanism and plays an important role in synergistic effect with adriamycin and cisplatin cytotoxicities.
Carcinoma, Renal Cell* ; Cell Line ; Cisplatin ; Doxorubicin ; Drug Therapy ; Fever* ; Glutathione Peroxidase ; Glutathione Transferase ; Glutathione* ; Humans* ; P-Glycoprotein* ; Transferases

Mitochondrial dysfunction is closely associated with reactive oxygen species (ROS) generation and oxidative stress in cells. On the other hand, modulation of the cellular antioxidant defense system by changes in the mitochondrial DNA (mtDNA) content is largely unknown. To determine the relationship between the cellular mtDNA content and defense system against oxidative stress, this study examined a set of myoblasts containing a depleted or reverted mtDNA content. A change in the cellular mtDNA content modulated the expression of antioxidant enzymes in myoblasts. In particular, the expression and activity of glutathione peroxidase (GPx) and catalase were inversely correlated with the mtDNA content in myoblasts. The depletion of mtDNA decreased both the reduced glutathione (GSH) and oxidized glutathione (GSSG) slightly, whereas the cellular redox status, as assessed by the GSH/GSSG ratio, was similar to that of the control. Interestingly, the steady-state level of the intracellular ROS, which depends on the reciprocal actions between ROS generation and detoxification, was reduced significantly and the lethality induced by H₂O₂ was alleviated by mtDNA depletion in myoblasts. Therefore, these results suggest that the ROS homeostasis and antioxidant enzymes are modulated by the cellular mtDNA content and that the increased expression and activity of GPx and catalase through the depletion of mtDNA are closely associated with an alleviation of the oxidative stress in myoblasts.
Catalase ; DNA, Mitochondrial ; Glutathione ; Glutathione Disulfide ; Glutathione Peroxidase ; Hand ; Homeostasis ; Myoblasts ; Oxidation-Reduction ; Oxidative Stress ; Reactive Oxygen Species