• Nutrition Research and Practice
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• v.9 no.6
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• pp.592-598
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• 2015

BACKGROUND/OBJECTIVES: Increased mass of adipose tissue in obese persons is caused by excessive adipogenesis, which is elaborately controlled by an array of transcription factors. Inhibition of adipogenesis by diverse plant-derived substances has been explored. The aim of the current study was to examine the effects of the aqueous methanol extract of laver (Porphyra yezoensis) on adipogenesis and apoptosis in 3T3-L1 adipocytes and to investigate the mechanism underlying the effect of the laver extract. MATERIALS/METHODS: 3T3-L1 cells were treated with various concentrations of laver extract in differentiation medium. Lipid accumulation, expression of adipogenic proteins, including CCAAT enhancer-binding protein ${\alpha}$, peroxisome proliferator-activated receptor ${\gamma}$, fatty acid binding protein 4, and fatty acid synthase, cell viability, apoptosis, and the total content and the ratio of reduced to oxidized forms of glutathione (GSH/GSSG) were analyzed. RESULTS: Treatment with laver extract resulted in a significant decrease in lipid accumulation in 3T3-L1 adipocytes, which showed correlation with a reduction in expression of adipogenic proteins. Treatment with laver extract also resulted in a decrease in the viability of preadipocytes and an increase in the apoptosis of mature adipocytes. Treatment with laver extract led to exacerbated depletion of cellular glutathione and abolished the transient increase in GSH/GSSG ratio during adipogenesis in 3T3-L1 adipocytes. CONCLUSION: Results of our study demonstrated that treatment with the laver extract caused inhibition of adipogenesis, a decrease in proliferation of preadipocytes, and an increase in the apoptosis of mature adipocytes. It appears that these effects were caused by increasing oxidative stress, as demonstrated by the depletion and oxidation of the cellular glutathione pool in the extract-treated adipocytes. Our results suggest that a prooxidant role of laver extract is associated with its antiadipogenic and proapoptotic effects.

• Nutrition Research and Practice
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• v.3 no.3
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• pp.185-191
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• 2009

The elevated level of circulating estradiol increases the risk of breast tumor development. To gain further insight into mechanisms involved in their actions, we investigated the molecular mechanisms of 4-hydroxyestradiol (4-$OHE_2$) to initiate and/or promote abnormal cell growth, and of $\alpha$- or $\gamma$-tocopherol to inhibit this process. MCF-10A, human breast epithelial cells were incubated with $0.1{\mu}M$ 4-$OHE_2$, either with or without $30{\mu}M$ tocopherols for 96 h. 4-$OHE_2$ caused the accumulation of intracellular ROS, while cellular GSH/GSSG ratio and MnSOD protein levels were decreased, indicating that there was an oxidative burden. 4-$OHE_2$ treatment also changed the levels of DNA repair proteins, BRCA1 and PARP-1. $\gamma$-Tocopherol suppressed the 4-$OHE_2$-induced increases in ROS, GSH/GSSG ratio, and MnSOD protein expression, while $\alpha$-tocopherol up-regulated BRCA1 and PARP-1 protein expression. In conclusion, 4-$OHE_2$ increases oxidative stress reducing the level of proteins related to DNA repair. Tocopherols suppressed oxidative stress by scavenging ROS or up-regulating DNA repair elements.

• BMB Reports
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• v.34 no.4
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• pp.316-321
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• 2001

Dehydroascorbate (DHA) reductase (DHAR, EC 1.8.5.1) catalyzes the reduction of DHA to reduced ascorbate (AsA) using glutathione (GSH) as the electron donor in order to maintain an appropriate level of ascorbate in plant cells. To analyze the physiological role of DHAR in environmental stress adaptation, we developed transgenic tobacco (Nicotiana tabacum cv. Xanthi) plants that express a human DHAR gene isolated from the human fetal liver cDNA library in the chloroplasts. We also investigated the DHAR activity, levels of ascorbate, and GSH. Two transgenic plants were successfully developed by Agrobacterium-mediated transformation and were confirmed by PCR and Southern blot analysis. DHAR activity and AsA content in mature leaves of transgenic plants were approximately 1.41 and 1.95 times higher than in the non-transgenic (NT) plants, respectively In addition, the content of oxidized glutathione (GSSG) in transgenic plants was approximately 2.95 times higher than in the NT plants. The ratios of AsA to DHA and GSSG to GSH were changed by overexpression of DHAR, as expected, even though the total content of ascorbate and glutathione was not significantly changed. When tobacco leaf discs were subjected to methyl viologen at $5\;{\mu}M$, $T_0$ transgenic plants showed about a 50% reduction in membrane damage compared to the NT plants.

• Clinical and Experimental Pediatrics
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• v.63 no.8
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• pp.314-320
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• 2020

Background: The accumulation of unpaired α-globin chains in patients with β-thalassemia major may clinically create ineffective erythropoiesis, hemolysis, and chronic anemia. Multiple blood transfusions and iron overload cause cellular oxidative damage. However, α-tocopherol, an antioxidant, is a potent scavenger of lipid radicals in the membranes of red blood cells (RBCs) of patients with β-thalassemia major. Purpose: To evaluate the effects of α-tocopherol on hemolysis and oxidative stress markers on the RBC membranes of patients with β-thalassemia major. Methods: Forty subjects included in this randomized controlled trial were allocated to the placebo and α-tocopherol groups. Doses of α-tocopherol were based on Institute of Medicine recommendations: 4-8 years old, 200 mg/day; 9-13 years old, 400 mg/day; 14-18 years old, 600 mg/day. Hemolysis, oxidative stress, and antioxidant variables were evaluated before and after 4-week α-tocopherol or placebo treatment, performed before blood transfusions. Results: Significant enhancements in plasma haptoglobin were noted in the α-tocopherol group (3.01 mg/dL; range, 0.60-42.42 mg/dL; P=0.021). However, there was no significant intergroup difference in osmotic fragility test results; hemopexin, malondialdehyde, reduced glutathione (GSH), or oxidized glutathione (GSSG) levels; or GSH/GSSG ratio. Conclusion: Use of α-tocopherol could indirectly improve hemolysis and haptoglobin levels. However, it played no significant role in oxidative stress or as an endogen antioxidant marker in β-thalassemia major.

• Biomedical Science Letters
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• v.6 no.1
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• pp.45-53
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• 2000

The anti-oxidative effects of Korean red ginseng extracts (total saponine, water extracts, alcohol extracts, lipophilic extracts), which were administered with the concentration of 200 mg/kg BW, were investigated after the injection of paraquat (1,1-dimethyl-4,4-bipyrimidinium dichloride: PQ) with dosage of 100 mg/kg BW on the peritoneal cavity to 6 weeks of 23~26 gm ICR male mice. The accumulation of hydrogen peroxide ($H_2O$$_2$) on the liver of mouse was lowered only in alcohol extract-treated group (p<0.05). The activity of glutathione peroxidase increased in the mouse treated with lipophilic ginseng extracts. And GSSG level was lowered in all groups, and this might be due to the paraquat ions that might prevent the reaction of GSSG into GSH. But we cannot find any relation between glutathione oxide-reductase activity on Korean ginseng extracts. Finally, the lipid peroxidation (MDA) level was lowest (p<0.01) in the group of mouse treated with water extracts of ginseng.

• Journal of Acupuncture Research
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• v.36 no.3
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• pp.140-146
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• 2019

Background: This study investigated the effects of Vipera lebetina turanica snake venom (SV) on cerebral infarction induced by middle cerebral artery occlusion in mice. Methods: Following cerebral infarction, SV was injected intravenously or added to BV2 cell culture. Tissue injury was detected using triphenyltetrazolium chloride (TTC) staining, neurological deficit score, NO, ROS, and GSH/GSSG assays, qPCR, Western blot, and cell viability. Results: Cerebral infarction caused by middle cerebral artery occlusion as observed by TTC staining, showed SV inhibited cell death, reducing the number of brain cells injured due to infarction. SV treatment for cerebral infarction showed a significant decrease in abnormal behavior, as determined by the neurological deficit score. The oxidation and inflammation of the cells that had cerebral infarction caused by middle cerebral artery occlusion (NO assay, ROS, GSH/GSSG assay, and qPCR), showed significant protection by SV. Western blot of brain infarction cells showed the expression of iNOS, COX-2, p-IkB-${\alpha}$, P38, p-JNK, p-ERK to be lower in the SV group. In addition, the expression of IkB increased. BV2 cells were viable when treated with SV at $20{\mu}g/mL$ or less. Western blot of BV2 cells, treated with 0.625, 1.5, $2.5{\mu}g/mL$ of SV, showed a significant decrease in the expression of p-IkB-${\alpha}$, p-JNK, iNOS, and COX-2 on BV2 cells induced by LPS. Conclusion: SV showed anti-inflammatory and anti-oxidant effects against cerebral infarction and inflammation.

• Anatomy and Cell Biology
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• v.57 no.1
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• pp.70-84
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• 2024

Methamphetamine (METH) can potentially disrupt neurotransmitters activities in the central nervous system (CNS) and cause neurotoxicity through various pathways. These pathways include increased production of reactive nitrogen and oxygen species, hypothermia, and induction of mitochondrial apoptosis. In this study, we investigated the long-term effects of METH addiction on the structural changes in the amygdala of postmortem human brains and the involvement of the brain- cAMP response element-binding protein/brain-derived neurotrophic factor (CREB/BDNF) and Akt-1/GSK3 signaling pathways. We examined ten male postmortem brains, comparing control subjects with chronic METH users, using immunohistochemistry, real-time polymerase chain reaction (to measure levels of CREB, BDNF, Akt-1, GSK3, and tumor necrosis factor-α [TNF-α]), Tunnel assay, stereology, and assays for reactive oxygen species (ROS), glutathione disulfide (GSSG), and glutathione peroxidase (GPX). The findings revealed that METH significantly reduced the expression of BDNF, CREB, Akt-1, and GPX while increasing the levels of GSSG, ROS, RIPK3, GSK3, and TNF-α. Furthermore, METH-induced inflammation and neurodegeneration in the amygdala, with ROS production mediated by the CREB/BDNF and Akt-1/GSK3 signaling pathways.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.335-345
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• 1996

A critical role of oxygen-derived free radicals has been implicated in ischemia/reperfusion (I/R)-induced brain damage. In this study, we have produced experimental I/R to the brains of Mongolian gerbil (Meriones unguiculatus) by a transient occlusion and release of the common carotid arteries. We have attempted to determine whether the oxidative stress is generated upon I/R and whether this oxidative stress is linked to the cell damage. Since hippocampus has been suggested as one of the most vulnerable regions of the brain to the oxidative stress, we analyzed samples from hippocampus in comparison with those from cortex. In addition, we have examined the expression of heat shock protein 70kD species (HSP70) in these regions in order to evaluate a possible role of this protein in I/R-induced brain damage. To determine whether the oxidative stress is produced upon I/R, we measured the glutathione oxidation, GSSG/ (GSH + 2xGSSG), as an index of oxidative stress. We found an increase of the glutathione oxidation primarily in hippocampus upon I/R. To determine whether this oxidative stress is linked to the cell damage, we measured the degree of lipid peroxidation upon I/R. We found an increase of lipid peroxidation in both regions. However, the magnitude of increases was greater in hippocampus than in cortex. In addition, we found that changes in both the magnitude and the temporal patterns of glutathione oxidation closely correlated with those of lipid peroxidation. Our study provides biochemical evidences that the oxidative stress is generated upon I/R and this oxidative stress is linked to the oxidative cell damage. Our study also provides evidences that the degree of oxidative stress as well as oxidative cell damage is greater in hippocampus than in cortex. We could not find difference in the basal level of HSP70 expression between hippocampus and cortex, indicating that the intrinsic vulnerability of hippocampus cannot be explained by the lower level of HSP70 expression. We did find, however, that the induction of HSP70 expression upon I/R was impaired in the hippocampus. This impairment appeared to be at the transcriptional level. These results suggest that the measurement of HSP70 induction may be employed as a useful predictor of differential cellular susceptibilities to the I/R-induced brain damage.

• Tuberculosis and Respiratory Diseases
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• v.39 no.1
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• pp.42-54
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• 1992

Background:It has been suggested that the cyclooxygenase metabolites play an important role in changes of early hemodynamic parameters in the endotoxin-induced acute lung injury. But there have been many debates about their role in the late increase of alveolar-capillary permeability, and it is not known whether they act directly or indirectly through oxygen free radicals which have been known to be produced during the metabolic process of cyclooxygenase pathway. So we performed this study to identify the pathogenetic role of cyclooxygenase metabolites in the endotoxin-induced acute lung injury in domestic pigs. Method: We infused endotoxin into 8 domestic pigs; endotoxin only (n=3), and pretreatment with indomethacin (n=5). We observed the sequential changes in hemodynamic parameters, the concentration of plasma oxidized glutathione (GSSG) in pulmonary arterial and venous blood, and albumin content in bronchoalveolar lavage fluid (BALF). Results: 1) While cardiac output decreased, mean pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen difference increased over phase 1 (0-2hr) and phase 2 (2-4.5hr) by endotoxin, indomethacin attenuated the decrease in cardiac output during phase 1 and increase in mean pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen difference during both phases. 2) The increase in plasma GSSG content during phase 2 was not attenuated by indomethacin. 3) The content of BALF albumin was significantly lower in indomethacin groups than that of endotoxin group. Conclusion: These results suggest that it is likely that cyclooxygenase metabolites have an effect on endotoxin-induced acute lung injury during both phases probably through direct action.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.6
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• pp.1058-1064
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• 2002

The purpose of this study was to investigate the effects of green tea on hepatic antioxidative defense system and recovery of muscle fatigue in rat after aerobic exercise. Male Sprague-Dawley rats weighing 150$\pm$ 10 g were randomly assigned to one normal (N) group and aerobic exercise training groups. Exercise training groups were classified into two groups: training (T) group and green tea (TG) group which were supplemented the distilled water and green tea extracts by dringking water during experimental periods, respectively. The experimental rats in exercise training groups (T and TG) ran on a treadmill 30 min/day at a speed of 28 m/min (7% incline) 5 days/week or were cage confined (Normal group) for 4 weeks. And rats were sacrificed with an overdose of pentobarbital injection just after running. Hepatic xanthine oxidase (XOD) activities were not significantly different among three groups. The activity of superoxide dismutase (SOD) in T group was no significant difference from N group, but those of TG groups were significantly increased, compared with that of T group. Hepatic glutathione peroxidase (GSHpx) activites of TG groups showed a similar tendency to that of normal group, but it was increased to 20% in TG group, compared with normal group. The reduced glutathione (GSH) contents in liver was not significantly different from that of any three group. The oxidized glutathione (GSSG) contents in T group was increased to 69%, compared with the normal group, but TG group significantly decreased, compared with the T group. The ratio of GSH/GSSG in liver of T group was lower than that of normal group, but those of TG group was a similar tendency to that of normal group. Contents of thiobarbituric acid reactive substance(TBARS) in T group was increased to 52%, compared with that of normal group but those of TG group were recovered the normal level. Contents of hepatic glycogen in T group were decreased to 23% compared with those of normal group, while that of TG group was the same as normal levels. The contents of serum lactic acid in T group were increased to 261%, compared with normal group, but those of TG group maintained the normal level by green tea supplementations. In conclusion, the effects of green tea in exercise training rats would appear to reduce peroxidation of tissue as an antioxidative defense mechanism and promote recovery of muscle fatigue.