Hyo-Yeon Kim

Ferulic acid protects against carbon tetrachloride-induced liver injury in mice

Ferulic acid (FA), isolated from the root of Scrophularia buergeriana, is a phenolic compound possessing antioxidant, anticancer, and antiinflammatory activities. Here, we have investigated the hepatoprotective effect of FA against carbon tetrachloride (CCl(4))-induced acute liver injury. Mice were treated intraperitoneally with vehicle or FA (20, 40, and 80mg/kg) 1h before and 2h after CCl(4) (20μl/kg) injection. The serum activities of aminotransferases and the hepatic level of malondialdehyde were significantly higher after CCl(4) treatment, while the concentration of reduced glutathione was lower. These changes were attenuated by FA. The serum level and mRNA expression of tumor necrosis factor-α significantly increased after CCl(4) treatment, and FA attenuated these increases. The levels of inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expression after CCl(4) treatment were significantly higher and FA reduced these increases. CCl(4)-treated mice showed increased nuclear translocation of nuclear factor-κB (NF-κB), and decreased levels of inhibitors of NF-κB in cytosol. Also, CCl(4) significantly increased the level of phosphorylated JNK and p38 mitogen-activated protein (MAP) kinase, and nuclear translocation of activated c-Jun. FA significantly attenuated these changes. We also found that acute CCl(4) challenge induced TLR4, TLR2, and TLR9 protein and mRNA expression, and FA significantly inhibited TLR4 expression. These results suggest that FA protects from CCl(4)-induced acute liver injury through reduction of oxidative damage and inflammatory signaling pathways.

Activation of NLRP3 and AIM2 inflammasomes in Kupffer cells in hepatic ischemia/reperfusion

Inflammasome activation by danger signals in ischemia/reperfusion (I/R) injury is responsible for the sterile inflammatory response. Signals triggering formation and activation of the inflammasome involve the generation of oxidative stress. The aim of this study was to examine the molecular mechanisms of inflammasome activation and the involvement of reactive oxygen species in hepatic I/R. I/R induced the formation of nucleotide‐binding domain leucine‐rich repeat containing family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes and the subsequent serum release of interleukin 1β. Pannexin‐1 inhibitor and anti‐cathepsin B antibody attenuated I/R‐induced inflammasome activation and hepatic injury. The expression of the thioredoxin‐interacting protein gene and the interaction between NLRP3 and the thioredoxin‐interacting protein increased after I/R. Treatment with the antioxidant N‐acetylcysteine significantly attenuated protein conversion of interleukin 1β after hepatic I/R. Moreover, pannexin‐1 protein expression and cathepsin B release were strongly attenuated by N‐acetylcysteine. The depletion of Kupffer cells with gadolinium chloride markedly decreased NLRP3 and AIM2 inflammasome expression and activation of their signaling pathways, and also reduced the level of caspase‐1 protein in F4/80‐positive cells. Our findings suggest that reactive‐oxygen‐species‐mediated activation of NLRP3 and AIM2 inflammasomes leads to I/R‐induced inflammatory responses in which Kupffer cells play a crucial role.

Immunomodulating effects of Korean mistletoe lectin in vitro and in vivo.

The immunomodulatory effects of Korean mistletoe lectin (KML), one of the major active components in Viscum album L. var. coloratum, were investigated in vitro in immune cell proliferation and natural killer (NK) cell- and macrophage-mediated cytotoxicity, and in vivo in the forced swim test and cold stress. In mitogen-induced lymphocyte proliferation of murine splenocytes, concanavalin A and lipopolysaccharide significantly increased the proliferation of T cell and B cell lymphocytes, respectively. KML exposure increased lymphocyte proliferation in response to mitogen. KML also increased the splenic NK cell and macrophage activities in vitro. Exposure to KML increased production of cytokines such as interleukin-1 and interleukin-6 by macrophages. Two-week treatment with KML (30, 100, 300 and 600 microg/kg) increased the recruitment of lymphocytes, monocytes and macrophages. In the forced swim test, the immobility time was significantly attenuated by treatment with KML (300 and 600 microg/kg). In a cold stress experiment, spleen and thymus weight increased in KML-treated mice, while the weight of adrenal gland was lower than that in vehicle-treated mice. The levels of serum aminotransferases, lactate dehydrogenase and alkaline phosphatase were decreased by KML treatment. KML treatment also induced increases in the percentages of CD4(+) and CD8(+) cells in thymus. Our results suggest that KML enhances the immune system through modulation of lymphocytes, NK cells, and macrophages.

Ferulic acid attenuates ischemia/reperfusion-induced hepatocyte apoptosis via inhibition of JNK activation.

Ferulic acid (FA), a phenolic compound found in various medicinal plants, has hepatoprotective effects against oxidative stress and inflammation. Here, we investigated the protective effects and the specific mechanisms of FA against hepatocyte apoptosis caused by ischemia/reperfusion (I/R). Mice were treated intraperitoneally with vehicle or FA 30 min prior to 60 min of ischemia. After 5h of reperfusion, serum aminotransferase activities and hepatic lipid peroxidation were elevated and hepatic glutathione content was depleted. These alterations were attenuated by FA. I/R increased caspase-3 activity and release of cytochrome c, and these were suppressed by FA. FA also attenuated the increases in the serum tumor necrosis factor (TNF)-α levels and TNF receptor type 1-associated DEATH domain protein and TNF receptor-associated factor 2 protein expressions. The cytosolic levels of Bcl-2-associated X protein (Bax), truncated BH3 interacting domain death agonist (tBid), and Bcl-2-like protein 11 were upregulated after reperfusion. The increases in Bax and tBid protein expression were attenuated by FA. Moreover, I/R induced c-Jun N-terminal kinase 1 (JNK1) and JNK2 phosphorylation, and FA attenuated the JNK activation. FA protects against I/R-induced hepatocyte apoptosis by attenuating oxidative stress and JNK activation.

A study on the etch characteristics of ITO thin film using inductively coupled plasmas

Abstract In this study, the high-density plasma etching of indium tin oxide (ITO) films used for transparent electrodes in display devices have been investigated. The etch characteristics of ITO as a function of Ar/CH4 gas mixtures were analyzed using quadrupole mass spectrometry (QMS), optical emission spectroscopy (OES), and electrostatic probe (ESP). ITO etch rates were increased with the addition of moderate amount of CH4 to Ar due to the increased chemical reaction between CH3 or H and ITO in addition to the physical sputtering of ITO by Ar ion bombardment. However, the addition of excess amounts of CH4 decreased the ITO etch rates, possibly due to the increased polymer formation on the ITO surface. Also, the data obtained by QMS and OES suggested that CH3 radicals are more actively involved in the etching of ITO compared to H radicals.

Clinical association between serum γ-glutamyltransferase levels and the development of insulin resistance in Korean men: a 5-year follow-up study

In recent years, γ‐glutamyltransferase has emerged as a predictor of cardiovascular disease, Type 2 diabetes mellitus, the metabolic syndrome and hypertension. However, it is not yet certain whether γ‐glutamyltransferase is a predictor for insulin resistance. The aim of this study was to examine the longitudinal association between baseline γ‐glutamyltransferase level and the development of insulin resistance in Korean men.

Protective effects of HV-P411 complex against D-galactosamine-induced hepatotoxicity in rats.

This study examined the hepatoprotective effect of the HV-P411 complex, an herbal extract mixture from the seeds of Vitis vinifera, Schisandra chinensis and Taraxacum officinale, against D-galactosamine (D-GalN)-induced hepatitis. Hepatotoxicity was induced by D-GalN (700 mg/kg, i.p.), and the HV-P411 complex was administered orally 48, 24, and 2 h before and 6 h after D-GalN injection. Increases in serum aminotransferase activity and lipid peroxidation and a decrease in hepatic glutathione content were attenuated by the HV-P411 complex 24 h after D-GalN treatment. The HV-P411 complex attenuated the increases in serum tumor necrosis factor-α, interleukin (IL)-6 level and cyclooxygenase-2 protein production and their mRNA expressions, while increases in serum IL-10 level and heme oxygenase-1 protein production and their mRNA expressions were augmented by the HV-P411 complex. The increased translocation of nuclear factor-κB and c-Jun phosphorylation were attenuated by treatment with the HV-P411 complex. Our results suggest that the HV-P411 complex prevents D-GalN-induced hepatotoxicity via antioxidative and anti-inflammatory activities.