• Title/Summary/Keyword: Free radicals

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Induction of Lipin1 by ROS-Dependent SREBP-2 Activation

  • Seo, Kyuhwa;Shin, Sang Mi
    • Toxicological Research
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    • v.33 no.3
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    • pp.219-224
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    • 2017
  • Lipin1 was identified as a phosphatidate phosphatase enzyme, and it plays a key role in lipid metabolism. Since free radicals contribute to metabolic diseases in the liver, this study investigated the effects of free radicals on the regulation of Lipin1 expression in Huh7 and AML12 cells. Hydrogen peroxide induced mRNA and protein expression of Lipin1 in Huh7 cells, which was assayed by quantitative RT-PCR and immunoblotting, respectively. Induction of Lipin1 by hydrogen peroxide was confirmed in AML12 cells. Hydrogen peroxide treatment significantly increased expression of sterol regulatory element-binding protein (SREBP)-2, but not SREBP-1. Moreover, nuclear translocation of SREBP-2 was detected after hydrogen peroxide treatment. Hydrogen peroxide-induced Lipin1 or SREBP-2 expression was significantly reduced by N-acetyl-$\small{L}$-cysteine treatment, indicating that reactive oxygen species (ROS) were implicated in Lipin1 expression. Next, we investigated whether the hypoxic environments that cause endogenous ROS production in mitochondria in metabolic diseases affect the expression of Lipin1. Exposure to hypoxia also increased Lipin1 expression. In contrast, pretreatment with antioxidants attenuated hypoxia-induced Lipin1 expression. Collectively, our results show that ROS activate SREBP-2, which induces Lipin1 expression.

Effect and Histopatbologic Examination of Calcium Channel Blocker on Carbon Tetrachloride-induced Hepatotoxicity in Rats (Calcium Channel Blocker가 사염화탄소에 의한 간손상에 미치는 영향 및 조직학적 검경)

  • 전명애;정춘식;정기화
    • Biomolecules & Therapeutics
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    • v.6 no.3
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    • pp.247-255
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    • 1998
  • Carbon tetrachloride (CCI$_4$) induces the hepatotoxicity due to the reactive free radicals generated by cytochrome P-450 (CYP-450) enzyme, which result in destabilization of cellular membrane. Diltiazem, a calcium channel blocking agent, has been known to suppress the CYP-450 enzyme activities. To study the effect of diltiazem in $CCl_4$-treated rats, we measured the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutathione S-transferase (GST), contents of bilirubin, albumin, total protein, cholesterol, triglyceride, blood urea nitrogen, creatinine malondialdehyde and calcium. Also we conducted liver histopathologic examinations. Diltiazem, when administered 1 hour prior to CCI$_4$ treaeent, significantly reduced the activities of ALT and AST, the contents of microsomal malondialdehyde and calcium in liver and microsome as compared with those of $CCl_4$-treated rats. In addition, histopathologic examination showed that diltiazem prevented the development of centrilobular necrosis induced by CCI$_4$ in liver tissue. Our results suggested that diltiazem could inhibit the formation of free radicals and the influx of calcium. Therefore diltiazem may be applied to suppress the liver damage caused by $CCl_4$.

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The Effect of Lidocaine and Procainamide on the Hepatic Aldehyde Oxidase Activity (알데히드 옥시다제의 활성에 미치는 리도카인 및 프로카인아미드의 영향)

  • Huh, Keun;Kim, Jin-Sook;Jin, Da-Qing;Ha, Eun-Pil;Lee, Sang-Il;Yong, Chul-Soon
    • YAKHAK HOEJI
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    • v.43 no.6
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    • pp.756-761
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    • 1999
  • Lipid peroxidation mediated by hydroxyl radicals which are generated during myocardial ischermia has suggested as a possible mechanism of ischemic myocardial damage. Recently, it has been reported that anti-arrhythmic action of lidocaine, a local anesthetic, is attributed to its "membrane-stabilizing" properties through scavenging free radicals, thus, inhibiting lipid peroxidation. Aldehyde oxidase and xanthine oxidase which catalyze the oxidation of many purine, pyrimidine and pteridine derivatives are known as free radical generating systems. In this experiment, we studied the effect of lidocaine and procainamide on the hepatic aldehyde and xanthine oxidase activity and antioxidative activities. It was found that lidocaine and procainamide inhibited both NADPH-dependent and independent lipid peroxidation. Both of tested compounds were found to be ineffective in inhibiting xanthine oxidase. Lidocaine and procainamide, however, inhibited aldehyde oxidase activity in vitro as well as in vivo. Based on the above results, lidocaine and procainamide could be employed as a therapeutic agent for aldehyde oxidaserelated disease.d disease.

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Characteristics of Polymer irradiated by Low energy Ion Beam

  • sung Han;Yoon, Ki-Hyun;Jung, Hyung-Jin;Koh, Seok-Keun
    • Proceedings of the Korean Vacuum Society Conference
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    • 1999.07a
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    • pp.109-109
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    • 1999
  • Recently, low energy ion beam irradiation has been adopted for surface modification. Low energy ion beam irradiation has many advantages in polymer engineering such as weak damage, good adhesion, noticeably-enhanced wettability(less than 15 degree), good reproducibility and so on. In this experiment, chemical reactions between free radicals and environment gas species have been investigated using angle-resolved XPS and TRIM code. In the case of low ion beam energy (around 1 keV), energy loss in polymer is mainly originated from atomic collisions instead of electronic interference. Atomic collisions could generated displaced atoms and free radicals. Cold cathode-ion source equipped with 5cm convex grid was used in an O2 environment. Base and working pressure were 5$\times$10-6 and 2.3$\times$10-4 Torr. Flow rates of argon and oxygen were fixed at 1.2 and 8 sccm. target materials are polyethylene polyvinyidenefluoride and polytetrafluoroethylene.

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Fingernail electron paramagnetic resonance dosimetry protocol for localized hand exposure accident

  • Jae Seok Kim;Byeong Ryong Park;Minsu Cho;Won Il Jang;Yong Kyun Kim
    • Nuclear Engineering and Technology
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    • v.55 no.1
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    • pp.270-277
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    • 2023
  • Exposure to ionizing radiation induces free radicals in human nails. These free radicals generate a radiation-induced signal (RIS) in electron paramagnetic resonance (EPR) spectroscopy. Compared with the RIS of tooth enamel samples, that in human nails is more affected by moisture and heat, but has the advantages of being sensitive to radiation and easy to collect. The fingernail as a biological sample is applicable in retrospective dosimetry in cases of localized hand exposure accidents. In this study, the dosimetric characteristics of fingernails were analyzed in fingernail clippings collected from Korean donors. The dose response, fading of radiation-induced and mechanically induced signals, treatment method for evaluation of background signal, minimum detectable dose, and minimum detectable mass were investigated to propose a fingernail-EPR dosimetry protocol. In addition, to validate the practicality of the protocol, blind and field experiments were performed in the laboratory and a non-destructive testing facility. The relative biases in the dose assessment result of the blind and field experiments were 8.43% and 21.68% on average between the reference and reconstructed doses. The results of this study suggest that fingernail-EPR dosimetry can be a useful method for the application of retrospective dosimetry in cases of radiological accidents.

Antioxidants as alleviating agents of in-vitro embryo production oxidative stress

  • Areeg Almubarak;Il-Jeoung Yu;Yubyeol Jeon
    • Journal of Animal Reproduction and Biotechnology
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    • v.38 no.2
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    • pp.47-53
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    • 2023
  • Despite numerous advances in in-vitro embryo production (IVP), many documented factors have been shown to influence the development of mammalian preimplantation embryos and the success of IVP. In this sense, elevated levels of reactive oxygen species (ROS) correlate with poor outcomes in assisted reproductive technologies (ART) due to oxidative stress (OS), which results from an imbalance between ROS production and neutralization. Indeed, excessive production of ROS compromises the structural and functional integrity of gametes and embryos both in vivo and in vitro. In particular, OS damages proteins, lipids, and DNA and accelerates cell apoptosis. Several in-vivo and in-vitro studies report an improvement in qualityrelevant parameters after the use of various antioxidants. In this review, we focus on OS and the source of free radicals and their effects on oocytes, sperm, and the embryo during IVP. In addition, antioxidants and their important role in IVP, supplementation during oocyte in vitro maturation (IVM), in vitro culture (IVC), and semen extenders were discussed. Nevertheless, various methods for determining the level of ROS in germ cells have been briefly described. Still, it is crucial to develop standardized antioxidant supplement systems to improve overall IVP success. Further studies should explore the safety, efficacy, mechanism of action, and combination of different antioxidants to improve IVP outcomes.

Cytotoxic Effect of Free Radical on Rat Primary Astrocytes (자유라디칼이 백서의 뇌별아교세포에 미치는 독성작용)

  • Jang, Hyuk;Kim, Myung-Sunny;Park, Hyun-Young;Kim, Yo-Sik;Cho, Kwang-Ho;Chung, Hun-Taeg;Park, Rae-Kil
    • Toxicological Research
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    • v.16 no.1
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    • pp.1-8
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    • 2000
  • Astrocytes generate free radicals including nitric oxide (NO) and reactive oxygen intermediates(ROI) which in turn play roles in the pathogenesis of degenerative diseases and sclerotic changes of the brain. This study was designed to evaluate the mechanism that free radicals contribute to the cytotoxicty of rat neonatal primary astrocytes. Treatment with NO donors alone including soldium nitroprusside(SNP), S-nitrosoglucathinoe (GSNO), and S-nitroso-n-acetylpenicillamine (SNAP) showed a little effect on the death of rat neonatal primary astrocytes, whereas SNP markedly induced the death of RAW 264.7 cells. ROI inculding H2O2 and O2 donor also slightly induced the death of rat primary astrocytes. However, 3-morpholinosydnonimine(SIN-1), a donor of peroxynitrite (ONOO), which is a reactive compound of NO with superoxide, significantly decreased the viability of rat primary astrocytes in a dose-dependent manner. Cells were retarded in outgrowth of viability of cellular processes with cell shrinkage and detachment from culture dishes. Hoechst staining demonstrated that SIN-1-induced cell death might be due to an apoptosis which was characterized by nuclear condensation and fragmentation. SIN-1-induced apoptosis was prevented by the pretreatment with superoxide dismutase (SOD) and catalase in rat primary astorocytes. Furthermore, prevention of the generation of reduced glutathione (GSH) by DL-buthionine-[S, R]-sulfoximine (BSO) aggravated the cytotoxic effects of SNP, benzene triol, and SIN-1 in rat primary astrocytes. Taken together, it is suggested that peroxynitrite may be a major effector of apoptosis and cellular antioxidant system is important for cell survival in rat prima교 astrocytes.

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Acanthopanax sessiliflorus stem confers increased resistance to environmental stresses and lifespan extension in Caenorhabditis elegans

  • Park, Jin-Kook;Kim, Chul-Kyu;Gong, Sang-Ki;Yu, A-Reum;Lee, Mi-Young;Park, Sang-Kyu
    • Nutrition Research and Practice
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    • v.8 no.5
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    • pp.526-532
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    • 2014
  • BACKGROUND/OBJECTIVES: Acanthopanax sessiliflorus is a native Korean plant and used as a traditional medicine or an ingredient in many Korean foods. The free radical theory of aging suggests that cellular oxidative stress caused by free radicals is the main cause of aging. Free radicals can be removed by cellular anti-oxidants. MATERIALS/METHODS: Here, we examined the anti-oxidant activity of Acanthopanax sessiliflorus extract both in vitro and in vivo. Survival of nematode C. elegans under stress conditions was also compared between control and Acanthopanax sessiliflorus extract-treated groups. Then, anti-aging effect of Acanthopanax sessiliflorus extract was monitored in C. elegans. RESULTS: Stem extract significantly reduced oxidative DNA damage in lymphocyte, which was not observed by leaves or root extract. Survival of C. elegans under oxidative-stress conditions was significantly enhanced by Acanthopanax sessiliflorus stem extract. In addition, Acanthopanax sessiliflorus stem increased resistance to other environmental stresses, including heat shock and ultraviolet irradiation. Treatment with Acanthopanax sessiliflorus stem extract significantly extended both mean and maximum lifespan in C. elegans. However, fertility was not affected by Acanthopanax sessiliflorus stem. CONCLUSION: Different parts of Acanthopanax sessiliflorus have different bioactivities and stem extract have strong anti-oxidant activity in both rat lymphocytes and C. elegans, and conferred a longevity phenotype without reduced reproduction in C. elegans, which provides conclusive evidence to support the free radical theory of aging.

Free Radical Scavenging Activity of Butanol Fraction from the Fruit of Citrus junos

  • Cho, Eun-Ju;Li, Li;Piao, Xiang-Lan;Lee, Sang-Hyun;Kim, Hyun-Young
    • Preventive Nutrition and Food Science
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    • v.14 no.1
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    • pp.86-89
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    • 2009
  • In this study, we investigated the free radical [1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical (${\cdot}OH$) and superoxide anion (${O_2}^-$)] scavenging activity of MeOH extract and 3 fractions of Citrus junos. Of the tested fractions, the BuOH fraction showed the strongest DPPH scavenging activity, showing the $IC_{50}$ values of 63.4 mg/mL. Therefore, we continuously carried out DPPH, ${\cdot}OH$ and ${O_2}^-$ scavenging activity tests of BuOH fraction of Citrus junos. The BuOH fraction of Citrus junos inhibited DPPH radical to 97.5% at a concentration of 1000 mg/mL and the scavenging activities were increased concentration-dependently. In addition, BuOH fraction from Citrus junos also scavenged ${\cdot}OH$ in a concentration dependent manner from 5 to 1000 mg/mL. Furthermore, BuOH fraction showed about 56% ${O_2}^-$-scavengimg activity at 25 mg/mL concentration but, the scavenging activities were not enhanced in a dose dependent manner. The present results suggest that BuOH fraction of Citrus junos would have the protective potential from oxidative stress induced by free radicals.

The Preventive Inhibition of Chondroitin Sulfate Against the $CCl_4$-Induced Oxidative Stress of Subcellular Level

  • Lee, Jin-Young;Lee, Sang-Hun;Kim, Hee-Jin;Ha, Jong-Myung;Lee, Sang-Hyun;Lee, Jae-Hwa;Ha, Bae-Jin
    • Archives of Pharmacal Research
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    • v.27 no.3
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    • pp.340-345
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    • 2004
  • Our work in this study was made in the microsomal fraction to evaluate the lipid peroxidation by measuring superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) and to elucidate the preventive role of CS in the $CCl_4$-induced oxidative stress. The excessive lipid peroxidation by free radicals derived from $CCl_4$ leads to the condition of oxidative stress which results in the accumulation of MDA. MDA is one of the end-products in the lipid peroxidation process and oxidative stress. MDA, lipid peroxide, produced in this oxidative stress causes various diseases related to aging and hepatotoxicity, etc. Normal cells have a number of enzymatic and nonenzymatic endogenous defense systems to protect themselves from reactive species. The enzymes in the defense systems, for example, are SOD, CAT, and GPx. They quickly eliminate reactive oxygen species (ROS) such as superoxide anion free radicalㆍO$^{[-10]}$ $_2$, hydrogen peroxide $H_2O$$_2$ and hydroxyl free radicalㆍOH. CS inhibited the accumulation of MDA and the deactivation of SOD, CAT and GPx in the dose-dependent and preventive manner. Our study suggests that CS might be a potential scavenger of free radicals in the oxidative stress originated from the lipid peroxidation of the liver cells of $CCl_4$-treated rats.