• Herbal Formula Science
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• v.8 no.1
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• pp.147-167
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• 2000

Reactive oxygen species (ROS) play an important role in the pathogenesis of a variety of life threatening conditions such as atherosclerosis, myocardial infarction and cerebral stroke. In this study, the effect of Sunghyangchungisan (SHCS) as a cytoproctant against ROS-induced cell injury was studied by investigating its effect on $H_{2}O_2-induced$ cell injury in cultured endothelial cells derived from the human umbilical vein. SHCS effectively proteced the cells against $H_{2}O_2-induced$ injury determined by trypan blue exclusion ability and lactate dehydrogenase (LDH) release. The effect of SHCS was concentration-dependent and the concentrations to inhibit by 50% the cell death and LDH release were $0.9{\pm}0.1$ and $1.2{\pm}0.1\;mg/ml$, respectively. In addition, SHCS effectively protected the cells against t-butylhydroperoside- and menadione-Induced injury as well. SHCS inhibited lipid peroxidation determined by malondialdehyde production. SHCS exerted as an effective scavenger of ROS produced by exposing the cells to $H_{2}O_2$ The activities of the intracellular ROS scavenging enzymes such as superoxide dismutase, catalase and glutathione peroxidase were not Influenced by SHCS.These results indicate that SHCS might exert as an effective cytoprotectant against ROS-induced cell injury. Further intensive studies would provide us insights into mechanisms of the pharmacological actions of SHCS.

• The Journal of Korean Medicine
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• v.27 no.2 s.66
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• pp.171-181
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• 2006

Objectives : Peroxynitrite($ONOO^-$), superoxide anion(${\cdot}{O_2}^-$) and nitric oxide (NO) is a cytotoxic species that can oxidize several cellular components such as proteins, lipids and DNA. It has been implicated in the aging process and age-related disease such as Alzheimer's disease, rheumatoid arthritis, cancer and atherosclerosis. The aim of this study was to investigate scavenging activities for $ONOO^-$ and its precursors, NO and ${\cdot}{O_2}^-$ of Vespae Nidus. Methods : Dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used to investigate scavenging activities of $ONOO^-,\;NO,\;{\cdot}{O_2}^-$. Six-months-old ICR mice were used. After mice were injected with lipopolysaccharides(LPS), kidney organization was evaluated. Three comparison groups of ICR mice were used : a normal group, an experimental group that was fed Vespae Nidus extract and then injected with LPS, and a control group that was injected with LPS. Scavenging activities of $ONOO^-,\;NO,\;{\cdot}{O_2}^-$ in these groups were measured in the same way. Results : Vespae Nidus markedly scavenged authentic $ONOO^-,\;{\cdot}{O_2}^-$ and NO. It also inhibited $ONOO^-$ induced by ${\cdot}{O_2}^-$ and NO which are derived trom SIN-1. Furthermore, it inhibited $ONOO^-,\;{\cdot}{O_2}^-$, and NO generation by Vespae Nidus in LPS-treated ICR mouse kidney postmitochondria. Conclusions : These results suggest that Vespae Nidus might be developed as an effective $ONOO^-,\;{\cdot}{O_2}^-$, and NO scavenger for the prevention of the aging process and age-related diseases.

• Environmental Analysis Health and Toxicology
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• v.14 no.3
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• pp.87-93
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• 1999

Antioxidative and scavenging effects were investigated by using two hyaroxycinnamic acids (caffeetannins). such as caffeic acid and chlorogenic acid, on oxidative stress and hepatotoxicity that induced by paraquat. The results are summerized as follows: 1. To assess radical scavenging ability, reduction concentration (IC$\sub$50/) of 1.1 diphenyl-2-dipicrylhydrazine (DPPH) were measured. IC$\sub$50/ values of caffeic acid and chlorogenic acid were 29.7 ${\pm}$0.6 ${\mu}$M and 26.0${\pm}$0.5 ${\mu}$M respectively. Their radical scavenging activities showed concentration-dependent manner. 2. In H$_2$O$_2$-induced hemolysis assay to rat blood, caffeic acid and chlorogenic acid led to different effects, whose hemolysis inhibition ratios at 100 ${\mu}$M were 45.2${\pm}$7.1% and 11.6${\pm}$3.1% respectively 3. In hypoxanthine-xanthine oxidase system producing superoxide anion, caffeic acid and chlorogenic acid showed different inhibitory activities of xanthine oxidase showing 36.8${\pm}$4.3% and 5.4${\pm}$2.3% respectively. 4. To microsomal NADPH dependent cytochrome p-450 reductase in rat liver, paraquat consumed NADPH at a dose-dependent manner from 0 to 1 ${\mu}$M paraquat concentration. Caffeic acid and chlorogenic acid blocked NADPH consumption rates at concentration-dependent manner and inhibition ratios at 100 ${\mu}$M were 67.6% and 59.2% respectively. 5. Administration (30mg/kg, iv) of paraquat to rats caused the marked elevation of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and lipid peroxides (LPO) in the serum and lipid peroxides in the microsome as compared to the control group. Serum GOT, GPT, LDH, ALP and LPO and liver microsomal LPO were reduced significantly by caffeic acid (50mg/kg), chlorogenic acid (25mg/kg) and silymarin (150 mg/kg) as compared to the paraquat group. From these results, caffeic acid and chlorogenic acid exerted their antioxidative agents by removing reactive oxygen substance (ROS) and scavenging effects by inhibiting ROS generating enzyme. As a general, two hydroxyeinnamic acids showed the useful compounds for scavenger and reducer on the paraquat induced hepatotoxicity.

• Reproductive and Developmental Biology
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• v.33 no.1
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• pp.49-54
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• 2009

The current study was designed to evaluate the effects of the reactive oxygen species (ROS) generated with a xanthine (X) and xanthine oxidase system (XO) on sperm function and DNA fragmentation in porcine spermatozoa. ROS were produced by a combination of $1,000{\mu}M$ X and 50 mU/ml XO. The ROS scavengers such as superoxide dismutase (SOD) (200 U/ml) and catalase (CAT) (500 U/ml) were also tested. Spermatozoa were incubated for 2 hours in BWW medium with a combination of X-XO supplemented with or without antioxidants at $37^{\circ}C$ under 5% $CO_2$ incubator. Ca-ionophore-induced acrosome reaction, the proportion of swollen spermatozoa under hypo-osmotic condition, malondialdehyde formation for the analysis of lipid peroxidation, and the proportion of DNA fragmentation were determined after 2 hours incubation. The action of ROS on porcine spermatozoa resulted in decreased Ca-ionophore-induced acrosome reaction and membrane integrity, increased the formation of malondialdehyde, and the proportion of sperm with DNA fragmentation(p<0.05). The toxic effects caused by ROS were completely alleviated by CAT in terms of sperm function and characteristics, however SOD did not serve the same scavenger effect as CAT. To conclude, the ROS can cause significant damage to porcine sperm functions and characteristics, which can be minimized by the use of antioxidants.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.3
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• pp.145-150
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• 2010

Adenosine (Ado) is an important mediator of the endogenous defense against ischemia-induced injury in the heart. The action of Ado is mediated by activation of G protein-gated inwardly rectifying $K^+$ (GIRK) channels. In turn, GIRK channels are inhibited by reducing phosphatidylinositol 4,5-bisphosphate ($PIP_2$) through Gq protein-coupled receptors (GqPCRs). We previously found that GIRK channels activated by acetylcholine, a muscarinic M2 acetylcholine receptor agonist, are inhibited by GqPCRs in a receptor-specific manner. However, it is not known whether GIRK channels activated by Ado signaling are also regulated by GqPCRs. Presently, this was investigated in mouse atrial myocytes using the patch clamp technique. GIRK channels were activated by $100\;{\mu}M$ Ado. When Ado was repetitively applied at intervals of 5~6 min, the amplitude of second Ado-activated GIRK currents ($I_{K(Ado)}$) was $88.3{\pm}3.7%$ of the first $I_{K(Ado)}$ in the control. Pretreatment of atrial myocytes with phenylephrine, endothelin-1, or bradykinin prior to a second application of Ado reduced the amplitude of the second $I_{K(Ado)}$ to $25.5{\pm}11.6%$, $30.5{\pm}5.6%$, and $96.0{\pm}2.7%$, respectively. The potency of $I_{K(Ado)}$ inhibition by GqPCRs was different with that observed in acetylcholine-activated GIRK currents ($I_{K(ACh)}$) (endothelin-1>phenylephrine>bradykinin). $I_{K(Ado)}$ was almost completely inhibited by $500\;{\mu}M$ of the $PIP_2$ scavenger neomycin, suggesting low $PIP_2$ affinity of $I_{K(Ado)}$. Taken together, these results suggest that the crosstalk between GqPCRs and the Ado-induced signaling pathway is receptor-specific. The differential change in $PIP_2$ affinity of GIRK channels activated by Ado and ACh may underlie, at least in part, their differential responses to GqPCR agonists.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2569-2574
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• 2015

Necroptosis, also known as "programmed necrosis", has emerged as a critical factor in a variety of pathological and physiological processes and is considered a cell type-specific tightly regulated process with mechanisms that may vary rather greatly due to the change of cell line. Here we used HT-29, a human colon cancer cell line, to establish a necroptosis model and elucidate associated mechanisms. We discovered that cobalt chloride, a reagent that could induce hypoxia-inducible $factor-1{\alpha}(HIF1{\alpha})$ expression and therefore mimic the hypoxic microenvironment of tumor tissue in some aspects induces necroptosis in HT-29 cells when caspase activity is compromised. On the other hand, apoptosis appears to be the predominant death form when caspases are functioning normally. HT-29 cells demonstrated significantly increased RIPK1, RIPK3 and MLKL expression in response to cobalt chloride plus z-VAD treatment, which was accompanied by drastically increased $IL1{\alpha}$ and IL6 expression, substantiating the notion that necrosis can induce profound immune reactions. The RIPK1 kinase inhibitor necrostatin-1 and the ROS scavenger NAC each could prevent necrosis in HT-29 cells and the efficiency was enhanced by combined treatment. Thus by building up a necroptosis model in human colon cancer cells, we uncovered that mechanically RIP kinases collaborate with ROS during necrosis promoted by cobalt chloride plus z-VAD, which leads to inflammation. Necroptosis may present a new target for therapeutic intervention in cancer cells that are resistant to apoptotic cell death.

• Journal of Korean Society of Environmental Engineers
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• v.32 no.3
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• pp.296-308
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• 2010

The peroxone process overcomes many of the limitations associated with conventional and advanced water treatment systems using chlorine disinfection and ozone oxidation processes. Ozone and hydrogen peroxide generate highly reactive hydroxyl free radical which oxidize various organic compounds and has highly removal efficiency. The key issue to operate peroxone process is developing the method to achieve high process effectiveness when scavengers that inhibit generation of OH radicals or consume OH radicals are co-existing in the process. Also many studies, to minimize inorganic oxidative by-products such as bromate and to reduce disinfection by-products after chlorination behind peroxone process, are needed. And we should consider the excess residual hydrogen peroxide in the water. On-line instruments and control strategies need to be developed to ensure effective and robust operation under conditions of varying load. If problems above mentioned are solved, peroxone process will be applied diversely for water treatment.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.2
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• pp.149-156
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• 2020

Sodium 2-mercaptoethanesulfonate (mesna) is a protective agent that is widely used in medicine because of its antioxidant effects. Recently, reactive oxygen species (ROS) were shown to increase pigmentation. Thus, ROS scavengers and inhibitors of ROS production may suppress melanogenesis. Forkhead box-O3a (FoxO3a) is an antimelanogenic factor that mediates ROS-induced skin pigmentation. In this study, we aimed to investigate the whitening effect of mesna and the signaling mechanism mediating this effect. Human melanoma (MNT-1) cells were used in this study. mRNA and protein expression were measured by real-time quantitative PCR and Western blotting analysis to track changes in FoxO3a-related signals induced by mesna. An immunofluorescence assay was performed to determine the nuclear translocation of FoxO3a. When MNT-1 melanoma cells were treated with mesna, melanin production and secretion decreased. These effects were accompanied by increases in FoxO3a activation and nuclear translocation, resulting in downregulation of four master genes of melanogenesis: MITF, TYR, TRP1, and TRP2. We found that mesna, an antioxidant and radical scavenger, suppresses melanin production and may therefore be a useful agent for the clinical treatment of hyperpigmentation disorders.

• Journal of Korean Neurosurgical Society
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• v.63 no.2
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• pp.171-177
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• 2020

Objective : To evaluate the neuroprotective effects of lacosamide after experimental peripheral nerve injury in rats. Methods : A total of 28 male wistar albino rats weighing 300-350 g were divided into four groups. In group I, the sciatic nerve exposed and the surgical wound was closed without injury; in group II, peripheral nerve injuries (PNI) was performed after dissection of the nerve; in group III, PNI was performed after dissection and lacosamide was administered, and in group IV, PNI was performed after dissection and physiological saline solution was administered. At 7 days after the injury all animals were sacrificed after walking track analysis. A 5 mL blood sample was drawn for biochemical analysis, and sciatic nerve tissues were removed for histopathological examination. Results : There is low tissue damage in lacosamide treated group and antioxidant anzymes and malondialdehyde levels were higher than non-treated and placebo treated group. However there was no improvement on clinical assessment. Conclusıon : The biochemical and histological analyses revealed that lacosamide has neuroprotective effect in PNI in rats. This neuroprotective capacity depends on its scavenger role for free oxygen radicals by increasing antioxidant enzyme activity.

• Journal of Nutrition and Health
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• v.34 no.7
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• pp.734-740
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• 2001

The purpose of this study was to investigate the effect of green tea catechins on the antioxidative defense enzyme activity of kidney in diabetic rats. Sprague-Dawley male rats weighting 100$\pm$10g were randomly assigned to one normal and three STZ-induced diabetic groups; catechin free diet(DM-0C group), 0.25% catechin diet(DM-0.25C group) and 0.5% catechin diet(DM-0.5C group). Diabetes was induced by intravenous of 55mg/Kg body weight of STZ in sodium citrate buffer(pH 4.3) after 4 weeks feeding of experimental diets. Rats were sacrified at the 6th day of diabetic states. Superoxide dismutase(SOD) activity in kidney was decreased by 25% and 20% in DM-0C and DM-0.25C groups compared with normal group, DM-0.5C group was not significantly different when compared with normal group. Glutathione peroxidase(GSHpx) activity in kidney was were no significant differences the diabetic groups compared to normal group. Xanthin oxidase(XOD) activity was increased by 110% and 63% in DM-0C and DM-0.25C groups compared with normal group, DM-0.5C group was not significantly different when compared with normal group. The contents of superoxide radical(O$_2$)in kindney were 116% and 33%, respectively, higher in DM-0C and DM-0.25C groups than normal group. DM-0.5C group and normal groups were similar levels in their superoxide radical contents of kidneys. Levels of TBARS(thiobarbituric acid reactive substance) in kidney were increased by 62% in DM-0C group, when compared with normal group, but those of DM-0.5C group were similar to that of normal groups. These results indicate that free radical generation system was weakened and free radical scavenger system was enhance in kidney of STZ-induced diabetics rats by dietary catechin. Thereby it may reduce renal disorders such as oxidative damage and aging of tissue.