• Title/Summary/Keyword: GPx

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Synergistic Renoprotective Effect of Melatonin and Zileuton by Inhibition of Ferroptosis via the AKT/mTOR/NRF2 Signaling in Kidney Injury and Fibrosis

  • Kyung Hee Jung;Sang Eun Kim;Han Gyeol Go;Yun Ji Lee;Min Seok Park;Soyeon Ko;Beom Seok Han;Young-Chan Yoon;Ye Jin Cho;Pureunchowon Lee;Sang-Ho Lee;Kipyo Kim;Soon-Sun Hong
    • Biomolecules & Therapeutics
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    • v.31 no.6
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    • pp.599-610
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    • 2023
  • According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis. Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.

In vitro approach to investigating the free radical generation of endocrine disruptor

  • Kim HJ;Kim BH;An KH
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2001.05a
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    • pp.117-117
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    • 2001
  • We investigated Free radical generation of endocrine disrupter, bisphenol A and alkyl esters of phthalic acid (DEP, DBP) using lipid peroxidation, enzyme assay (SOD, Catalase, Gpx-px), Cell viability and phototoxicity. Bisphenol A are monomers of various plastics including polycarbonates and epoxy resins which are used in numerous consumer products. The release of BPA from some of these materials has recently been reported. (omitted)

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Antioxidative effect of flavonol quercetin and hydrocaffeic acid against a oxidative stress on B16F10 murine melanoma cell of pretreated with hydrogen peroxide

  • Hue, Jeong-Sim;Kim, An-Keun
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.210.1-210.1
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    • 2003
  • In this study, we investigated the effect of inhibition of proliferation and antioxidant effect on B16F10 murine melanoma cell. Also, we examined by MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and intracellular reactive oxygen intermediate levels and the levels of catalase(CAT), superoxide dismutase (SOD), and glutathione peroxidase(GPX) an adaptive response of oxidative stress on B16F10 murine melanoma cell of pretreated with hydrogen peroxide. (omitted)

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Antioxidant effect of flavonoid, myricetin with GSH, vitamin E, vitamin C on B16F10, murine melanoma cell

  • Yu, Ji-Sun;Kim, An-Keun
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.144.2-145
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    • 2003
  • Reactive Oxygen Species (ROS) are produced during normal cellular function. ROS are very transient species due to their high chemical reactivity that leads to lipid peroxidation and oxidation of some enzyme, massive protein oxidation and degradation. Under normal conditions, antioxidant are substances that either directly or indirectly protect cells against adverse effects of ROS. Several biologically important compounds have been reported to have antioxidant functions. These incluce vitamin C, vitamin E, GSH, flavonoids. superoxidee dismutase(SOD), glutathione peroxidase(GPX) and catalase(CAT). (omitted)

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Antioxidant enzyme acitivity of flavonol quercetin in the presence of different anticxidants.

  • Hue, Jeong-Sim;Kim, An-Keun
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.159.3-160
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    • 2003
  • It has been known that quercetin is one of bioflavonid compounds and has anti-tumor effect by suppressing tumor growth in vitro and in vivo, including multiple biological effects by antioxidant and effective anti-inflammatory agent. The present study investigated whether quercetin can enhance antioxidant enzyme activity (glutathione proxidase: GPX, superoxide dismutase: SOD, catalase: CAT) and regulate the intracellular reactive oxygen intermediate levels on the B16F10 murine melanoma cells in the presensece of vitamin E, L-ascorbic acid (vitamin C) and reduced glutathione (GSH). (omitted)

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Hepatoprotective Effects of Saururus chinensis Baill against 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) Induced Toxicity

  • Lee, Sang-Hun;Kim, Hee-Jin;Lee, Jin-Young;Ha, Bae-Jin
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.211.2-211.2
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    • 2003
  • Saururus Chinensis Baill (Saururaceae) has been used as folk medicine for analgesics, beriberi, edema, hepatitis, and icterus, etc. Hepatoprotective effects of Saururus chinensis Baill (SCB) administration on function of the biochemical parameters in liver of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treated rats were investigated. After 7 days from TCDD(1$\mu\textrm{g}$/kg) injection, SCB(200mg/kg) was administered into rats intraperitoneally for 4 week.s We examined the antioxidative enzymatic activity by measuring the level of AST and ALT in serum and SOD, Catalase, GPx, GSH and GSSG in liver tissue of rats. (omitted)

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Antioxidant Enzyme Activity, Iron Content and Lipid Oxidation of Raw and Cooked Meat of Korean Native Chickens and Other Poultry

  • Muhlisin, Muhlisin;Utama, Dicky Tri;Lee, Jae Ho;Choi, Ji Hye;Lee, Sung Ki
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.5
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    • pp.695-701
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    • 2016
  • This study was conducted to observe antioxidant enzyme activity, iron content and lipid oxidation of Korean native chickens and other poultry. The breast and thigh meat of three Korean native chicken breeds including Woorimatdak, Hyunin black and Yeonsan ogye, and three commercial poultry breeds including the broiler, White Leghorn and Pekin duck (Anasplatyrhyncos domesticus) were studied. The analyses of the antioxidant enzymes activity, iron content and lipid oxidation were performed in raw and cooked samples. The activity of catalase (CAT) in the thigh meat was higher than that of the breast meat of three Korean native chickens and the broiler, respectively. The activity of glutathione peroxidase (GPx) in the uncooked thigh meat of three Korean native chickens was higher than that of the breasts. The breast meat of Woorimatdak and Pekin duck had higher superoxide dismutase (SOD) activity than the others, while only the thigh meat of Pekin duck had the highest activity. Cooking inactivated CAT and decreased the activity of GPx and SOD. The thigh meat of Woorimatdak, White Leghorn, Yeonsan ogye and Hyunin black contained more total iron than the breast meat of those breeds. The heme-iron lost during cooking ranged from 3.2% to 14.8%. It is noted that the thigh meat had higher thiobarbituric acid reactive substances values than the breast in all chicken breeds. Though Woorimatdak showed higher antioxidant enzyme activity and lower released-iron percentage among Korean native chickens, no differences were found on lipid oxidation. We confirm that the dark meat of poultry exhibited higher antioxidant enzyme activity and contained more iron than the white meat.

Effects of Soshiho-tang on Hydrogen Peroxide-induced Oxidative Damage in Hepatocytes (과산화수소로 유도된 산화성 간세포 손상에 대한 소시호탕(小柴胡湯)의 효과)

  • Seo, Sang-Hee;Oh, Su-Young;Lee, Ji-Seon;Cho, Won-Kyung;Kim, Tae-Soo;Ma, Jin-Yeul
    • The Journal of Internal Korean Medicine
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    • v.32 no.4
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    • pp.487-496
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    • 2011
  • Objectives : The aim of this study was to investigate the hepatoprotective effect of Soshiho-tang (SSH) in mouse primary liver cells against hydrogen peroxide ($H_2O_2$)-induced oxidative stress. We also elucidated the molecular mechanism of hepatoprotective effect by SSH. Methods : Cell viability, level of ALT, AST and LDH, intracellular ROS level, mRNA expression and activity of antioxidant enzymes were used to evaluate hepatoprotection of SSH against $H_2O_2$. Target gene expressions were analyzed by real-time PCR. Results : Pre-treatment with SSH for 1 hour prevented cytotoxicity against $H_2O_2$. $H_2O_2$-induced ROS level decreased under SSH pre-treatment. mRNA expression of GPx and SOD increased in SSH-treated cells. In addition, HSP72 and HSP40 gene expression were elevated under SSH-treatment. Conclusions : These results indicate that SSH protects mouse primary liver cells from $H_2O_2$-induced oxidative injury. This hepatoprotective activity of SSH is mediated by decreasing intracellular ROS and increasing antioxidant enzyme expression (GPx and SOD) and stress response protein (HSP72 and HSP40).

Effects of 4-tert-octylphenol on glutathione-related antioxidant status in olive flounder Paralichthys olivaceus

  • Jee, Jung-Hoon;Keum, Yoo-Hwa;Bae, Jun Sung;Lee, Chae Won;Yang, Chan Yeong;Choi, Sang-Hoon;Kang, Ju-Chan;Park, Kwan Ha
    • Journal of fish pathology
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    • v.32 no.2
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    • pp.113-121
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    • 2019
  • Effects on glutathione-related antioxidant parameters were examined after a chronic exposure of olive flounder, Paralichthys olivaceus to dietary 4-tert-octylphenol (4-tert-OP). Fish were fed diets containing 4-tert-OP at 0, 1, 5 and 10 mg/kg diet for 6 weeks. Antioxidant parameters examined were reduced glutathione (GSH) contents and enzyme activities of glutathione reductase (GR), glutathione S-transferase (GST) and glutathione peroxidase (GPx) in tissue homogenates of the liver, kidney and gill. It was observed that all parameters examined increased although there were some differences in dose responses and temporal patterns in the increase. GSH contents increased after exposure to 4-tert-OP in the three organs examined. However, the GSH increase was evident only after 4 weeks in the liver whereas it was elevated after 2 weeks in the kidney and gill. GR activity exhibited a significant increase in response to 4-tert-OP at 1 mg/kg in all three organs, however, its activity returned to control levels when exposed to 5 and 10 mg/kg. Hepatic GST activity showed an earlier increase at week 2 in contrast to the kidney and gill where they increased after 4 weeks of 4-tert-OP exposure. Temporal patterns in GPx activity changes to 4-tert-OP exposure were dissimilar among the organs: hepatic activity increased from week 2 through week 6; renal activity increased transiently at week 2; gill levels were higher through weeks 4 - 6. The results suggest that elevation of several GSH-related antioxidant parameters can be considered as evaluation criteria for 4-tert-OP-induced oxidative stress in a fish.