• BMB Reports
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• v.49 no.5
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• pp.288-292
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• 2016

Cisplatin is a platinum-based chemotherapeutic drug for treating various types of cancers. However, the use of cisplatin is limited by its negative effect on normal tissues, particularly nephrotoxicity. Various mechanisms such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and apoptosis are involved in the adverse effect induced by cisplatin treatment. Several studies have suggested that neuropeptide Y (NPY) is involved in neuroprotection as well as restoration of bone marrow dysfunction from chemotherapy induced nerve injury. However, the role of NPY in chemotherapy-induced nephrotoxicity has not been studied. Here, we show that NPY rescues renal dysfunction by reducing the expression of pro-apoptotic proteins in cisplatin induced nephrotoxicity through Y1 receptor, suggesting that NPY can protect kidney against cisplatin nephrotoxicity as a possible useful agent to prevent and treat cisplatin-induced nephrotoxicity.

• YAKHAK HOEJI
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• v.39 no.3
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• pp.231-242
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• 1995

Electroconvulsive shock (ECS) increases the activity of acetylchohnesterase and decreases in brain acetylcholine levels. A large amount of free fatty acids accumulated in the brain tissue affects cerebral blood flow, brain edema and inflammation and results in brain injury. The present study examined the effect of docosahexaenoic acid (DHA) and D,L-pyroglutamic acid (D,L-PCA) on the learning and memory deficit using the passive avoidance failure technique and on the change of acetylcholine and choline level in the cerebral cortex of ECS-induced mice. The application of ECS (25mA, 0.5sec) induced a significant decrease in memory function for 30 min. ECS-induced a significant decrease in cortical acetylcholine and choline levels 1 min following the ECS application, which were almost recovered to ECS control level after 30 min. DHA (20 mg/kg, i.p.). administered 24 hr before shock. prevented the ECS-induced passive avoidance failure and the decrease of acetylcholine level 1 min following the ECS application. DHA failed to elicit a change in cortical choline level. DHA did not affect memory function and the cortical Ach and choline level of normal mice. The administration of D,L-PCA (500 mg/kg, i.p.) increased the effect of DHA on memory function and the change of cortical acetylcholine level of ECS induced mice. These results suggest that DHA treatment may be contributed to the prevention against memory deficit, and to the activation of cholinergic system in the ECS induced mice.

• Preventive Nutrition and Food Science
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• v.1 no.1
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• pp.64-68
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• 1996

Chromosomal aberration tests in vitro using Chinese hamster lung(CHL) cells were carried out to evaluate the possible role of the MeOH extract of Ecklonia stolonifera in modulating the chromosomal damage induced by Mitomycin C(MMC) and Benzo(a)pyrene(B(a)P), respectively. The MeOH extract of Ecklonia stolonifera(260$\mu\textrm{g}$/ml) reduced significantly the incidence of chromosomal aberration induced by treatment with B(a)P by 80%. The suppressive effect was much stronger than that of $\beta$-carotene, which is well known antimu-tagen. However, there was no marked decrease in the chromosomal aberration induced by MMC. In the tests involving chromosomal aberration induced by the treatment of the MeOH extract of Exklonia stlolnifera alone, there was no significant increase in comparison with the negative control. The results would seem to indicate that. at least under the conditions examined, the MeOH extract of Ecklonis stolonifera decreased the chromosomal aberrations induced by B(a)P in the CHL cells, but had little effect on the chromosomal aberration induced by MMC.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.572-582
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• 2023

Background: Free fatty acid-induced lipotoxicity is considered to play an important role in pancreatic β-cell dysfunction. The effect of ginsenosides on palmitic acid-induced pancreatic beta-cells cell death and failure of glucose-stimulated secretion of insulin (GSIS) was evaluated in this study. Methods: Enzyme-linked immunosorbent assay kit for a rat insulin was used to quantify glucose-stimulated insulin secretion. Protein expression was examined by western blotting analysis. Nuclear condensation was measured by staining with Hoechst 33342 stain. Apoptotic cell death was assessed by staining with Annexin V. Oil Red O staining was used to measure lipid accumulation. Results: We screened ginsenosides to prevent palmitic acid-induced cell death and impairment of GSIS in INS-1 pancreatic β-cells and identified protopanaxadiol (PPD) as a potential therapeutic agent. The protection effect of PPD was likely due to a reduction in apoptosis and lipid accumulation. PPD attenuated the palmitic acid-induced increase in the levels of B-cell lymphoma-2-associated X/B-cell lymphoma 2, poly (ADP-ribose) polymerase and cleaved caspase-3. Moreover, PPD prevented palmitic acid-induced impairment of insulin secretion, which was accompanied by an increase in the activation of phosphatidylinositol 3-kinase, peroxisome proliferator-activated receptor γ, insulin receptor substrate-2, serine-threonine kinase, and pancreatic and duodenal homeobox-1. Conclusion: Our results suggest that the protective effect of PPD on lipotoxicity and lipid accumulation induced by palmitic acid in pancreatic β-cells.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.1
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• pp.31-36
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• 2013

The present study was undertaken to investigate the influence of eupatilin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Eupatilin more significantly relaxed fluoride-induced vascular contraction than thromboxane $A_2$ or phorbol ester-induced contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, eupatilin significantly inhibited fluoride-induced increases in pMYPT1 levels. On the other hand, it didn't significantly inhibit phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the primarily inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1. This study provides evidence regarding the mechanism underlying the relaxation effect of eupatilin on agonist-induced vascular contraction regardless of endothelial function.

• Preventive Nutrition and Food Science
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• v.18 no.1
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• pp.11-17
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• 2013

Dysfunction of endothelial cells is considered a major cause of vascular complications in diabetes. In the present study, we investigated the protective effect of Padina arborescens extract against high glucose-induced oxidative damage in human umbilical vein endothelial cells (HUVECs). High-concentration of glucose (30 mM) treatment induced cytotoxicity whereas Padina arborescens extract protected the cells from high glucose-induced damage and significantly restored cell viability. In addition, lipid peroxidation, intracellular reactive oxygen species (ROS), and nitric oxide (NO) levels induced by high glucose treatment were effectively inhibited by treatment of Padina arborescens extract in a dose-dependent manner. High glucose treatment also induced the overexpressions of inducible nitric oxide synthase (iNOS), cyclooxygenase- 2 (COX-2) and NF-${\kappa}B$ proteins in HUVECs, but Padina arborescens extract treatment reduced the over-expressions of these proteins. These findings indicate the potential benefits of Padina arborescens extract as a valuable source in reducing the oxidative damage induced by high glucose.

• Toxicological Research
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• v.32 no.4
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• pp.345-351
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• 2016

Propolis is a resinous material collected by honeybees from several plant sources. This research aimed at showing its protective effect against UVA-induced apoptosis of human keratinocyte HaCaT cells. Using Hoechst staining, it was demonstrated that propolis (5 and $10{\mu}g/mL$) significantly inhibited the apoptosis of HaCaT cells induced by UVA-irradiation. Propolis also showed the protective effect against loss of mitochondrial membrane potential induced by UVA-irradiaiton in HaCaT cells. Propolis also inhibited the expression of activated caspase-3 induced by UVA-irradiation. To investigate the role of ROS in UVA-induced apoptosis and protection by propolis, the generation of ROS was determined in cells. The results showed that the generation of ROS was markedly reduced in cells pretreated with propolis. Consequently, propolis protected human keratinocyte HaCaT cells against UVA-induced apoptosis, which might be related to the reduction of ROS generation by UVA-irradiation.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.4
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• pp.447-454
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• 1999

The production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) are known to be modulated by a variety of factors. Recent study showed that endotoxin-induced NO synthesis and iNOS expression were greatly enhanced by elevation of extracellular glucose concentration in murine macrophages. Although this was suggested to be due to the activation of protein kinase C (PKC) via sorbitol pathway, there was lack of evidence for this speculation. This study was performed to delineate the underlying intracellular mechanisms of glucose-enhancing effect on endotoxin-induced NO production in Raw264.7 macrophages. The levels of NO release induced by lipopolysaccharide (LPS) significantly increased by the treatment of glucose in a concentration dependent manner and also, this effect was observed in LPS-preprimed cells. Concurrent incubation of cells with PKC inhibitors, H-7 or chelerythrine, and LPS resulted in the diminution of NO production regardless of glucose concentration but this was not in the case of LPS-prepriming, that is, chelerythrine showed a minimal effect on the glucose- enhancing effect. PMA, a PKC activator, did not show any significant effect on glucose-associated NO production. Modulation of sorbitol pathway with zopolrestat, an aldose reductase inhibitor, did not affect LPS-induced NO production and iNOS expression under high glucose condition. And also, sodium pyruvate, which is expected to normalize cytosolic $NADH/NAD^+$ ratio, did not show any significant effect at concentrations of up to 10 mM. Glucosamine marginally increased the endotoxin-induced nitrite release in both control and high glucose treated group. 6-diazo-5-oxonorleucine (L-DON) and azaserine, glutamine: fructose- 6-phosphate amidotransferase (GFAT) inhibitors, significantly diminished the augmentation effect of high glucose on endotoxin-induced NO production. On the other hand, negative modulation of GFAT inhibitors was not reversed by the treatment of glucosamine, suggesting the minimal involvement, if any, of glucosamine pathway in glucose-enhancing effect. In summary, these results strongly suggest that the hexosamine biosynthesis pathway and the activation of PKC via sorbitol pathway do not contribute to the augmenting effect of high glucose on endotoxin induced NO production in macrophage-like Raw264.7 cells.

• The Korean Journal of Pain
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• v.29 no.4
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• pp.229-238
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• 2016

Background: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. Methods: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ($[Ca^{2+}]_i$) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. Results: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in $[Ca^{2+}]_i$. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. Conclusions: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.

• The Journal of Korean Medicine
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• v.25 no.4
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• pp.61-78
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• 2004

Objective : This study was undertaken to determine whether Gamibaegi-eum (BGU) in vitro and in vivo exerts a beneficial effect against cell injury induced by reactive oxygen species (ROS) in the human intestine. Methods : Effects of BGU in vitro on cell injury were examined using Caco-2 cells, cultured human intestinal cell line. Exposure of cells to H₂O₂ induced increases in the loss of cell viability in a time and dose-dependent fashion. Results : BGU prevented H₂O₂-induced cell death and its effect was dose-dependent over a concentration range of 0.05­1%. H₂O₂-induced cell death was prevented by catalase, the hydrogen peroxide scavenger enzyme, and deferoxamine, the iron chelator. However, the potent antioxidant DPPD did not affect H₂O₂-induced cell death. H₂O₂ increased lipid peroxidation, which was inhibited by BGU and DPPD. H₂O₂ caused DNA damage in a dose-dependent manner, which was prevented by BGU, catalase, and deferoxamine, but not DPPD. BGU restored ATP depletion induced by H₂O₂. BGU inhibited generation of superoxide and H₂O₂ and scavenged directly H₂O₂. Oral administration of mepirizole in vivo at a dose of 200mg/kg resulted in ulcer lesions in the stomach and the proximal duodenum. Pretreatment of BGU(0.1%/kg, orally) and catalase (800Units/kg, i.v.) significantly decreased the size of ulcers. Mepirizole increased lipid peroxidation in the mucosa of the duodenum, suggesting an involvement of ROS. Pretreatment of BGU and catalase significantly inhibited lipid peroxidation induced by mepirizole. Morphological studies showed that mepirizole treatment causes duodenal injury and its effect is prevented by BGU. Conclusion : These results indicate that BGU exerts a protective effect against cell injury in vitro and in vivo through antioxidant action. The present study suggests that BGU may playa therapeutic role in the treatment of human gastrointestinal diseases mediated by ROS.