• Title/Summary/Keyword: Glutathione peroxidase GPX1

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Ferroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis

  • Hasan Dirik;Ahmet Sevki Taskiran;Ziad Joha
    • The Korean Journal of Pain
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    • v.37 no.3
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    • pp.233-246
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    • 2024
  • Background: Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats. Methods: This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG. Results: After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001). Conclusions: The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.

Effect of Selenium on the Thyroid gland Antioxidative Metabolisms in Rat Model by Ionizing Radiation (셀레늄이 전리방사선에 의한 힌쥐 모델에서의 갑상선 항산화계에 미치는 영향)

  • Choi, Hyung-Seok;Choi, Jun-Hyeok;Jung, Do-Young;Kim, Jang-Oh;Shin, Ji-Hye;Min, Byung-In
    • Journal of radiological science and technology
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    • v.40 no.1
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    • pp.135-142
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    • 2017
  • Selenium (Se), which is natural materials existing was known as an important component of selenoprotein, one of the important proteins responsible for the redox pump of a living body. Selenium was orally administered to Rat and irradiated with 10 Gy of radiation. Then, the thyroid gland was used as a target organ for 1 day, 7 days and 21 days to investigate the radiation protection effect of selenium (Se) through changes of blood components, thyroid hormones (T3, T4), antioxidant enzyme (GPx) activity and thyroid tissue changes. As a result, there was a significant protective effect of hematopoietic immune system(hemoglobin concentration, neutrophil, platelet)(p<0.05). The activity of Glutathione Peroxidase (GPx), the antioxidant enzyme, and the activity of the target organ, thyroid hormone (T3, T4), also showed significant activity changes (p<0.05). In the observation of tissue changes, it was confirmed that there was a protective effect of thyroid cell damage which caused the cell necrosis by radiation treatment. Therefore, it is considered that selenium(Se) can be utilized as a radiation defense agent by inducing immunogenic activity effect of a living body.

Excess Taurine Induced Placental Glutathione S-transferase Positive Foci Formation in Rat

  • Kweon, Sang-Hui;Kim, Yoon;Choi, Hay-Mie;Kwon, Woo-Jung;Chang, Kyung-Ja
    • BMB Reports
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    • v.33 no.6
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    • pp.469-475
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    • 2000
  • The purpose of this study was to examine the chemopreventive potential of taurine at various levels on the diethylnitrosamine (DEN)·induced hepatocarcinogenesis. Male Sprague-Dawley rats were fed on diets containing 0, 1, 2, 3% taurine or 5% ${\beta}-alanine$ for taurine depletion. Then they were treated with DEN and 2/3 partial hepatectomy. The number of placental glutathione S-transferase positive ($GST-P^+$) foci, as a preneoplastic marker in the 1 % taurine group was lower than the control diet group. However the difference was insignificant. Although taurine diets reduced the thiobarbituric acid reactive substance (TBARS) level, the number of $GST-P^+$ foci was increased in 3% taurine diet group. The 1 % taurine diet increased the glutathione (GSH) level and GST activity, however they unfortunately did not suppress the foci formation. In the 3% taurine group, the GSH level and GSH peroxidase (GPx) activity were significantly decreased. Excess taurine supplementation of the pharmaceutical dose worked against hepatic chemoprevention, which might result from modulation of GPx activity and GSH utility. On the contrary, taurine might work as an antioxidant against TBARS production as the 1 % taurine diet increased GSH level. The potency of the cancer preventive effect of taurine still remains and further studies should investigate the effect of taurine with less than 1 % levels on the prevention of hepatic cancer.

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Esculetin Inhibits Adipogenesis and Increases Antioxidant Activity during Adipocyte Differentiation in 3T3-L1 Cells

  • Kim, Younghwa;Lee, Junsoo
    • Preventive Nutrition and Food Science
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    • v.22 no.2
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    • pp.118-123
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    • 2017
  • This study was conducted to investigate the anti-adipogenic activity of esculetin (ECT) which is reported to be attributable to the modulation of antioxidant enzymes during adipogenesis. After six days of ECT treatment of 3T3-L1 cells, lipid accumulation was determined by Oil red O staining. The levels of glutathione (GSH) and reactive oxygen species (ROS), and the activities of antioxidant enzymes including glutathione reductase, glutathione peroxidase (GPx), and catalase were examined. In addition, the protein expression of glutamate-cysteine ligase catalytic subunit (GCLC) and heme oxygenase-1 (HO-1) was measured by Western blot. ECT significantly inhibited lipid accumulation by approximately 80% and ROS production in a concentration-dependent manner. GSH level and GPx activity were increased by ECT by approximately 1.3-fold and 1.7-fold compared to the control group, respectively. GCLC and HO-1 expression were elevated by ECT. These results showed that ECT treatments strongly inhibit adipogenesis, increase GSH level, and upregulate the expression of GCLC and HO-1, possibly by decreasing ROS production in 3T3-L1 cells during adipogenesis.

Protective Effect of Angelicae Dahuri Radix on Hypoxia Reperfusion Induced by PC12 Cell Damage and Global Ischemia in Gerbil (PC12 손상 세포 및 전뇌허혈 유발 Gerbil에 대한 백지의 세포보호효과)

  • 이영효;정승현;신길조;문일수;이원철
    • The Journal of Korean Medicine
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    • v.24 no.1
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    • pp.110-121
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    • 2003
  • Objective : This research was performed to investigate the protective effect of Angelicae Dahuri Radix against ischemic damage using PC12 cells and global ischemia in gerbils. Methods : To observe the protective effect of Angelicae Dahuri Radix on ischemia damage, viability and changes in activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase and production of malondialdehyde (MDA) were observed after treating PC12 cells with Angelicae Dahuri Radix during ischemic insult. Gerbils were divided into three groups : a normal group, a 5-min two-vessel occlusion (2VO) group, and an Angelicae Dahuri Radix administered after 2VO group. The CCAs were occluded by microclip for 5 minutes. Angelicae Dahuri Radix was administered orally for 7 days after 2VO. The histological analysis was performed at 7 days after surgery. For histological analysis, the brain tissue was stained with 1% cresyl violet solution. Results : 1. Angelicae Dahuri Radix has a protective effect against ischemia in the CA1 area of the gerbil hippocampus 7 days after 5-minute occlusion, 2. In the hypoxia/reperfusion model using PC12 cells, Angelicae Dahuri Radix has a protective effect against ischemia in the dose of $0.2\mu\textrm{g}/ml$, $2\mu\textrm{g}/ml$ and $20\mu\textrm{g}/ml$, 3. Angelicae Dahuri Radix increased the activities of glutathione peroxidase and catalase. 4. The activity of superoxide dismutase (SOD) was increased by ischemic damage, which might represent self protection. This study suggests that Angelicae Dahuri Radix has some neuroprotective effect against neuronal damage following cerebral ischemia in vivo with a widely used experimental model of cerebral ischemia in Mongolian gerbils, and it also has protective effects on a hypoxia/reperfusion cell culture model using PC12 cells. Conclusions : Angelicae Dahuri Radix has protective effects against ischemic brain damage at the early stage of ischemia.

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Protective Effect of Rhizoma Dioscoreae on the Gastric Mucosal Lesions Induced by Alcohol in Rats (산약이 알콜로 유도된 흰쥐의 위 점막 손상 예방에 미치는 영향)

  • Jeong, Yong-Yeon;Lee, Young-Su
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.3
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    • pp.639-644
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    • 2009
  • The aim of this study was carried out to investigate the protective effect of Rhizoma Dioscoreae on the gastric mucosal lesions induced by alcohol in rats. Experimental groups were treated by oral infusion with Rhizoma Dioscoreae extract at the dose of 0.03465 g/ml(OA-RD1 group), 0.0693 g/ml(OA-RD2 group), and 0.1386 g/ml(OA-RD3 group), while D.W group was administrated with the distilled water and control group did not pretreated. Experimental groups pretreated for 14 days, and given orally 1 ml of 75% alcohol two times(30min interval). The animals were killed 1hr 30min after alcohol treatment, and measured rats body weight, absolute stomach weight, relative stomach weight, SOD activity, glutathione peroxidase(GPx) activity, observed gastric mucosal lesions. The body weight was unremarkable changed. In once as dose intake group's absolute stomach weight was increased and In once as dose intake group, twice as dose intake group's relative stomach weight was increased. SOD activity, glutathione peroxidase activity in twice as dose intake group is remarkably increased. Light microscopy Observations of congestion, hemorrhage, and erosion in gastric mucosal lesions were shown severely in control group than OA-RD1, OA-RD2, OA-RD3. These results suggest that the proposed gastroprotective effect may involve activation of antioxidant effect. And Twice as dose is especially effective.

Susceptibility of Cigarette Smoke Condensate-Exposed Human Bronchial Epithelial Cells to Hypoxia-Reoxygenation (담배연기 농축액 처리에 의해 유도된 사람 기관지 상피세포주의 Hypoxia-Reoxygenation에 대한 민감성)

  • Lee, In-Ja;Choi, Eun-Mi
    • Environmental Analysis Health and Toxicology
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    • v.24 no.1
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    • pp.53-61
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    • 2009
  • 사람 기관지상피세포주인 BEAS-2B에 담배연기농축액(CSC)을 처리하여 유도된 1198 세포주는 대조군 세포주인 1799에 비해 현저하게 낮은 glutathione 농도와 낮은 glutamate-cysteine ligase(GCL), glutathione peroxidase(GPx), glucose-6-phosphate dehydrogenase(G6PD), catalase 효소활성을 보였다. 두 세포주를 포도당 존재 하에서 4시간 hypoxia 처리 후 reoxygenation 하면서 시간에 따른 세포의 항산화계 활성을 측정한 결과, 1799 세포주에서는 의미 있는 변화가 관찰되지 않은 반면, 1198 세포주에서는 hypoxia 처리에 의해 glutathione의 농도 및 GSH/GSSG 비와 G6PD 활성이 감소되었고, reoxygenation 기에는 GPx, glutathione reductase(GRd), G6PD, superoxide dismutase 활성이 감소되었다. 그러나 reoxygenation 2시간 이후에는 GRd와 G6PD 활성의 회복이 관찰되었으며, 그 결과 GSH/GSSG 비율이 회복되었다. 이 실험 결과는 CSC가 능력을 현저히 저하시킬 수 있음을 보여준다. Glutathione은 hypoxia-reoxygenation에 의한 산화적 스트레스 하에서 항산화제로서의 역할뿐 아니라, 세포 내 GSH/GSSG 비의 변화를 통해 산화적 스트레스에 대한 항산화계의 적응 반응 여부를 결정하는 중요한 인자로 작용할 것으로 보여진다.

Protective effects of Opuntia ficus-indica on Glutathione and Antioxidative Enzyme (Opuntia ficus-indica가 Glutathione 및 항산화 효소에 미치는 보호효과)

  • 전홍기;정영기;하배진
    • Journal of Life Science
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    • v.13 no.6
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    • pp.911-916
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    • 2003
  • The effects of Opuntia ficus-indica (OF) administration on the biochemical parameters of function in liver tissue and serum of $CCl_4$ treated rats were investigated. Opuntia ficus-indica (200 mg/kg) was administered into rats intraperitoneally for two weeks. $3.3m\ell$ of $CCl_4$$_4$ (50% $CCl_4$ : Olive oil = 1 : 1) was treated to rats on the 14th day and 15th day and they were operated on 15th day. We examined the antioxidative enzymatic activity by measuring the level of AST (Aspartate aminotransferase), ALT (Alanine aminotransferase), GSH (Glutathione reduced form), GSSG (Glutathione oxidezed form), GPx (GSH-peroxidase), SOD (Superoxide dismutase) and CAT (Catalase) in serum and liver tissue of rats. OFC administered group showed 24.8% of inhibitory effect in AST activity compared to $CCl_4$ -treated abnormal group (CTA). ALT level of OF administered group was decreased by 60.7% to the level of CTA. GSH, GSSG and GPx of OFC administered group were significantly higher than those of CTA group. SOD and CAT in OFC administered group were increased by 28.3% and by 16.9% respectively compared to those of CTA group.

Protective Effect of Aurantii Immaturus Fructus on Hypoxia Reperfusion Induced by PC12 Cell Damage and Global Ischemia in Gerbil (PC12 손상 세포 및 전뇌허혈 유발 Gerbil에 대한 지실의 세포보호효과 연구)

  • 김완식;정승현;신길조;문일수;이원철
    • The Journal of Korean Medicine
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    • v.24 no.1
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    • pp.29-40
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    • 2003
  • Object : This research was performed to investigate the protective effect of Aurantii Immaturus Fructus against ischemic damage using PC12 cells and global ischemia in gerbils. Methods : To observe the protective effect of Aurantii Immaturus Fructus on ischemia damage, viability and changes in activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase and production of malondialdehyde (MDA) were observed after treating PC12 cells with Aurantii Immaturus Fructus during ischemic insult. Gerbils were divided into three groups : a normal group, a 5-min two-vessel occlusion (2VO) group, and an Aurantii Immaturus Fructus administered after 2VO group. The CCAs were occluded by microclip for 5 minutes. Aurantii Immaturus Fructus was administered orally for 7 days after 2VO. The histological analysis was performed at 7 days after the surgery. For histological analysis, the brain tissue was stained with 1% cresyl violet solution. Results : The results showed that 1. Aurantii Immaturus Fructus had a protective effect against ischemia in the CAI area of the gerbil hippocampus 7 days after 5-minute occlusion, 2. In the hypoxia/reperfusion model using PC12 cells, the Aurantii Immaturus Fructus had a protective effect against ischemia in the dose of $0.2{\;}\mu\textrm{g}/ml,{\;}2{\;}\mu\textrm{g}/ml{\;}and{\;}20{\;}\mu\textrm{g}/ml$ 3. Aurantii Immaturus Fructus increased the activities of glutathione peroxidase and catalase, 4. The activity of superoxide dismutase (SOD) was increased by ischemic damage, which might represent self protection. This study suggests that Aurantii Immaturus Fructus has some neuroprotective effect against neuronal damage following cerebral ischemia in vivo with a widely used experimental model of cerebral ischemia in Mongolian gerbils, and it also has protective effects on a hypoxia/reperfusion cell culture model using PCq2 cells. Conclusions : Aurantii Immaturus Fructus has protective effects against ischemic brain damage at the early stage of ischemia.

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Nitric oxide modulates antioxidant defense and the methylglyoxal detoxification system and reduces salinity-induced damage of wheat seedlings

  • Hasanuzzaman, Mirza;Hossain, Mohammad Anwar;Fujita, Masayuki
    • Plant Biotechnology Reports
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    • v.5 no.4
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    • pp.353-365
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    • 2011
  • The present study investigates the possible regulatory role of exogenous nitric oxide (NO) in antioxidant defense and methylglyoxal (MG) detoxification systems of wheat seedlings exposed to salt stress (150 and 300 mM NaCl, 4 days). Seedlings were pre-treated for 24 h with 1 mM sodium nitroprusside, a NO donor, and then subjected to salt stress. The ascorbate (AsA) content decreased significantly with increased salt stress. The amount of reduced glutathione (GSH) and glutathione disulfide (GSSG) and the GSH/GSSG ratio increased with an increase in the level of salt stress. The glutathione S-transferase (GST) activity increased significantly with severe salt stress (300 mM). The ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), catalase (CAT) and glutathione peroxidase (GPX) activities did not show significant changes in response to salt stress. The glutathione reductase (GR), glyoxalase I (Gly I), and glyoxalase II (Gly II) activities decreased upon the imposition of salt stress, especially at 300 mM NaCl, with a concomitant increase in the $H_2O_2$ and lipid peroxidation levels. Exogenous NO pretreatment of the seedlings had little influence on the nonenzymatic and enzymatic components compared to the seedlings of the untreated control. Further investigation revealed that NO pre-treatment had a synergistic effect; that is, the pre-treatment increased the AsA and GSH content and the GSH/GSSG ratio, as well as the activities of MDHAR, DHAR, GR, GST, GPX, Gly I, and Gly II in most of the seedlings subjected to salt stress. These results suggest that the exogenous application of NO rendered the plants more tolerant to salinity-induced oxidative damage by enhancing their antioxidant defense and MG detoxification systems.